Category: Metabolism

We all love to eat, in fact, it’s essential for us to eat. However, most people don’t actually seem to care about the amount they are taking into their bodies until it’s affecting them in a way they a not fond of. For example, you may be asking yourself why is so and so not getting fat and I am yet we eat about the same, or maybe you say to yourself okay so I’m not trying to lose weight, and I find my weight decreasing. These statements and questions that are formed tend to lead people to say, “I need to diet!” or “I need to eat more!”, only resulting in them jumping into this new journey without really understanding the why’s of it all except for the initial fact that “I want to lose or maintain my weight.” Our bodies actually have its own process of why this is going on and how you can fix it. This process is called metabolism. Your metabolism is not fixed and can be altered, it differs from person to person for a variety of reasons, is a key factor to losing and maintaining weight, and even if you are not struggling with either losing or maintaining weight it is still very essential in preventing this dissatisfaction with your body.

[bookmark: _Hlk1480332] Metabolism is a chemical reaction that breaks down the food and nutrients we eat and converts it into energy, that we use to fuel our bodies. It’s a comparable concept as a car needing gas to operate, or even plants needing sunlight to grow. Metabolism as a whole is a combination of two things going on, Anabolism and catabolism. According to Steven Dowshen, a medical professional, “Catabolism or destructive metabolism, is the process that produces the energy required for all activity in the cells. In this process, cells break down large molecules (mostly carbohydrates and fats) to release energy. This energy release provides fuel for anabolism, heats the body, and enables the muscles to contract and the body to move (Dowshen, 2015).” This is the first process that takes place in metabolism. Catabolism is what happens when you digest food. Foods must be broken down into smaller and more simple molecules so that they are usable for anabolism to take place. “Anabolism or constructive metabolism is all about building and storing: It supports the growth of new cells, the maintenance of body tissues, and the storage of energy for use in the future… (Dowshen, 2015).” This is the part of your metabolism you need to rebuild your broken-down molecules. This is also where you will find growth in bone and muscle mass take place. Both processes work hand in hand with each other to make up the metabolism process. A main takeaway from learning about these two processes is that catabolism is losing fat as well as muscle, but then anabolism is building and maintaining muscle while at the same time converting the stored fat into energy.

As I briefly mentioned before, metabolism isn’t fixed, but instead can be altered. Why might a person want to alter their metabolism? Because everyone’s metabolism is regulated at different rates. Some people burn fat very quickly and others store fat longer and take longer to burn the fat off. The speed at which you burn fat, and what determines if you have a fast or slow metabolism, are all up to your Thyroid. Your thyroid is a butterfly-shaped, endocrine gland that is located at the front of your neck, just below your Adam’s apple or you can compare it to the spot you would wear a bow tie. The thyroid gland’s main job is to regulate metabolism by producing hormones such as T3 and T4. Dr. Westin Child states, “Your thyroid gland, if working properly, produces around 80% T4 and about 20% T3(Childs 2018).” The amount of the hormone produced affects the rate your metabolism is regulated. Too much of the thyroid hormones produced (also known as hyperthyroidism) can cause your body to lose weight and speed up too much than perhaps needed. Too little of the thyroid’s hormones being produced (also known as hypothyroidism) can cause the body to be sluggish, gain weight, and slow down more than recommended.

If you are wanting to lose weight or maintain your weight there are many methods you can use to alter your metabolism rate, to speed up or slow down, in a healthy way. Two of these methods, being strength training and controlling insulin levels. Strength training is effective because this affects body mass which affects metabolism. According to Aleisha Fetters, a medical science major, “Every pound of muscle burns roughly six calories per day at rest…that’s about three times as many calories as a pound of fat (Fetters 2017).” This is true for most, however, people may vary in genetics, hormones, sleep, and diet. These are factors that can cause a person to have a harder time losing weight. Metabolic rate is tied to building muscle also because, Fetters says, “by having more muscle, you’ll also burn more calories…. That’s because you’ll be able to work harder and longer (Fetters 2017).” Therefore, we must keep muscle mass up to keep metabolism up. Another method to altering your metabolic rate is by controlling your insulin levels. Insulin is a hormone that is involved in regulating blood glucose and the storage of fat. The body uses insulin to take glucose out of the blood to use as energy. If the body is already sufficient in energy, glucose is still taken but stored in the liver as glycogen. When the liver has taken up as much glycogen as it can, the insulin then tells the fat cells to take some glucose and store it as triglycerides. Insulin can then signal the breakdown of fats. Some ways you can keep your insulin levels low are low carb diets, watching portion size, avoiding sugar, incorporating more exercise, taking in more cinnamon, intermittent fasting, drinking green tea, and many more. Get your insulin in check and that’s just another way your metabolic rate will be in check.

One thing about metabolism, that is not commonly adjusted, is BMR (basal metabolic rate). This is your metabolism rate while your body is at rest. The reason it cannot be adjusted easily is that this is a specific calculation that uses your height, weight, sex, and age. These are mostly genetic factors, something a person can’t control. The BMR calculation was made to tell us the number of calories our body is burning while we are doing absolutely nothing. If you are a woman, to find your BMR you would use BMR= 655+ (9.6x weight in Kg) + (1.8x height in Cm) – (4.7x age in years). For men you would use BMR = 66+ (13.7x weight in kg) + (5x height in cm) – (6.8x age in years). You might want to know why is this important to know before you do this complex math solution. Once you find your BMR you’ll know the number of calories you should be consuming in order to meet your goal of maintaining or losing weight. According to Scott Frothingham, author of the newsletter Healthline, if you want to maintain weight consume the same number of calories that you burn and If you want to lose weight consume fewer calories than you burn (Frothingham 2018). Now that you know your BMR and why it’s important, you need to consider how these numbers would differ during daily activity and not just at rest. To determine how active a person is they can look at a scale that starts at sedentary, then there is lightly active, moderately active, very active and highly active. Finding the category, you’re in will then give you the number you need to multiply to your BMR. Once that number is found you’ll see that the more active you are the more calories you need to intake because your body is burning fat at a faster rate than when you are less active.

Unfortunately, as you start to age your metabolism will slow down. Even after all your new lifestyle changes to keep your metabolism regulated, and to provide your body with a healthy lifestyle. Have you noticed that the older you get the more naps you take? This is because for most of us our bodies just aren’t fueled with the same energy because with aging comes fewer active levels. Stated by Ashley Brantley, writer of Well tuned, another thing that comes with aging is, “… our bodies don’t produce as much growth hormone, which is what’s largely responsible for building muscle mass and burning fat (Brantley 2019).” Older people experience a muscle loss called sarcopenia. Brantley says, “Physically inactive people can lose up to 3-8% of their muscle mass every decade after 30, which leads to decreased strength and mobility. That means a physically inactive person at age 60 may have 24% less muscle mass than they did at age 30, and often that lost muscle is replaced by fat (Brantley 2019).” The age at wich you see these aging factors take place in your metabolism doesn’t have a specific number, it just happens little by little varying from person to person according to their lifestyle leading up to aging. However, women can expect to see changes before men because of menopause. When a woman undergoes menopause her estrogen hormones decrease, causing the bodies regulatory system to accommodate for the loss of estrogen and paying less attention to your metabolic rate. Luckily just like when you were younger, you don’t have to sit back and watch your metabolism go downhill. You can improve your metabolism even with aging factors by, eating healthy fats and more protein diets, getting enough sleep to let your body regulate blood sugar from spiking and keeping your body hydrated.

So, you see to stay healthy it isn’t all about the numbers on the scale and how to magically make them change. To stay healthy, knowing how your metabolism plays a role is a key factor to a person’s healthy lifestyle and weight change journey. A person can’t just eat as much as they want to or not eat enough and expect their bodies to run its course in a positive way. Some people understand this process our bodies go through but still don’t get the result they want, and that’s when going to outside resources might be an option. Meeting with a certified health coach could be a helpful option because they can personally make diet plans that work specifically for you. This may be hard to do on your own because understanding nutrition is a whole different topic for a different day. Meeting with a certified personal trainer as well is helpful in learning the ropes of exercise. Above everything else it takes motivation. You have to have the willpower to want to see a metabolism change and stick with it all the way through. Rome wasn’t built in a day, and your metabolism won’t change overnight.

Works Cited

1. Brantley, Ashley. ‘How Does Your Metabolism Change As You Age?’ WellTuned by BCBST, 21 Feb. 2019, bcbstwelltuned.com/2019/02/12/how-does-your-metabolism-change-as-you-age/.
2. Childs, Westin. ‘T3 and T4 Hormone Guide: What They Mean, Optimal Levels & More.’ Dr. Westin Childs | Thyroid & Health Supplements That Work, 13 Apr. 2018, www.restartmed.com/t3-and-t4/.
3. Dowshen, Steven. ‘Metabolism (for Teens) – KidsHealth.’ KidsHealth – the Web’s Most Visited Site About Children’s Health, June 2015, kidshealth.org/en/teens/metabolism.html.
4. Frothingham, Scott. ‘What Is Basal Metabolic Rate?’ Healthline, 12 Nov. 2018, www.healthline.com/health/what-is-basal-metabolic-rate. Accessed 24 Feb. 2019.
5. K. Fetters, Aleisha. ‘How Much Does Strength Training Really Increase Metabolism?’ SELF, 21 Sept. 2017, www.self.com/story/how-much-does-strength-training-really-increase-metabolism.

Abstract

The practical was carried out to investigate the various forms of plant cell metabolism. The process of photosynthesis and fermentation was the main focus of the practical exercise. The first practice was on photosynthesis (the hill reaction) and variations in light intensity, light wavelength and inhibiting substances were investigated. The second practical focused on starch synthesis “the Dark reaction,” this is the light-independent stage of photosynthesis. In this experiment, the conversion of sugars to starch for storage is shown in the third experiment, fermentation was studied using fresh and boiled potato extracts and the yeast cell (Saccaromyces cerevisiae). The role of the fermentation process to provide energy for the yeast cells is shown in this experiment. The results were tabulated, analysed and discussed to understand the practical.

Introduction

Cellular metabolism is a complex process that occurs both in plants and animals. “The various processes that take place are catalysed by respective enzymes involved.” (Kamau, 145) Much of the metabolic activities are dedicated to generating energy for cellular activity. “Plants in particular manufacture food by the process of photosynthesis.” (Nelson 3) In the process carbon is converted to organic compounds using the sunlight, the organic compounds, which are mainly in form of sugars, are utilized as food by plants and animals. Photosynthesis takes place in chloroplasts; a lot of research has been done in the past to determine the different factors (for example, Light intensity and wavelength) that affect photosynthesis. Part of the present study aims at ascertaining the factors that play a role in photosynthesis.

Following photosynthesis, a biosynthetic process called the “the dark reaction” takes place in the matrix of the stroma, the process leads to the formation of other forms of sugar. (Allen, 145) Another metabolic process is fermentation. This is the conversion of carbohydrates to energy with the production of alcohols and acids. It involves transferring electrons obtained from the breakdown of nutrients back to molecules of the same nutrients. Fermentation is utilized to break down sugars and release energy among other products. In order to confirm the above cell metabolic activities, three experiments were set up: experiment one to investigate the hill reaction and effects due to variations in light intensity, wavelength and photosynthesis inhibiting chemical. Experiment two investigates the dark reaction phase of photosynthesis where by the energy is stored and can be retrieved when there is a shortage and experiment three investigate the process of fermentation.

Materials and Method

Materials

• Spectrophotometer
• Spectrophotometer cuvettes
• Phosphate buffer (pH6.5)
• Chloroplast suspension
• Sodium hydrosulfite
• Distilled water
• Wrapping foil
• DCMU
• 10nM glucose-1-phosphate
• Starch solution
• 1M KH2PO4
• Fresh potato extract
• Boiled potato extract
• 10% glucose
• 2% yeast suspension
• 2 Conical flasks
• Syringes

Procedure

Experiment 1: The hill reaction

Freshly boiled chloroplast suspension was obtained and allowed to return to room temperature. Four clean spectrophotometer cuvettes were obtained and labelled 1-4.

3.0 ml of Phosphate buffer (pH 6.5) and 1.0 ml of chloroplast suspension were added to each tube. Other solutions were added to the tubes respectively as indicated in the practical manual. The spectrophotometer was blanked and the tubes read at 600nm, the results were recorded.

The experiment was repeated with different variations in: Light intensity, light wavelength and the herbicide DCMU which inhibits photosynthesis

Experiment 2: Determination of starch synthesis in a potato

6 clean glass test tubes were obtained and labelled 1-6. 3 ml of 10mM glucose phosphate and 1 drop of 0.2% starch solution were added to tubes 1, 2, 3, 4, and 5. 3ml of distilled H2o, 0.1 ml of 0.2% starch solution and 0.2 ml of 1M KH2PO4 were added to tube 6. The tubes were treated respectively as indicated in the practical manual (with boiled and fresh potato extract). Iodine solution was added to the tubes and the colour changes were observed and recorded

Experiment 3: Cellular Fermentation in yeast

5ml of 10% glucose and 5ml of 2% yeast suspension was added to a conical tube which was then inverted to mix the suspension. Another conical flask was used to mix 5ml of distilled water with 5ml of 2% yeast solution. The flasks were incubated in a water bath at 40 degrees Celsius for 5min. Two syringes were labelled and the solutions were manipulated in them as indicated in the practical manual. The rate of fermentation of sugar was recorded graphically in the lab notebook.

Results

Experiment 1: photosynthesis, the hill reaction

Variations in conditions

Variation 1: effects of light intensity.

Experiment 2- Starch Synthesis in Potato

Lightest 2- Semi-dark 3- Darkest.

Experiment 3: cellular fermentation in yeast

Discussion

In the first experiment (the hill reaction), the rate of photosynthesis remained the same for cuvettes 1 and 3, there was no evidence of photosynthetic activity in the fourth cuvette. In cuvette 5, the photosynthetic activity decreased with time. With variation in light intensity, the photosynthetic process in all the cuvettes slowed down with a decrease in light intensity. This indicates that light is vital for the process of photosynthesis. The graph showed a slight change in the photosynthetic process as a result of a change in the light wavelength. In the third variation, the herbicide DCMU (3-(3-4-dichlorophenyl)-1, 1-dimethylurea) which inhibits photosynthesis by blocking electron transport from photo system. The DCMU affected the hill and seemed to be inhibiting the photosynthesis process. In the second practical to investigate starch synthesis (dark reaction), fresh and boiled potato extracts were used. In the fresh potato extracts, there was evidence of starch synthesis. The second practical intended to show that photosynthesis takes place in two phases, the light-dependent phase and the light-independent phase. In the first phase, there is capture and storage of energy in form of ATP and NADH. In the second stage, the captured energy is used to process starch. When the energy is produced by photosynthesis is not sufficient for the plant’s metabolic activities, the starch is converted back to sugar to provide for the deficit. In the practical, the process of making starch was performed by placing a primer in the presence of sugar and enzyme phosphorylase. Iodine was used to indicate the presence of starch.

In the third practical where the cellular fermentation of different sugars was to be determined, the results were as follows: The fermentation for galactose short up over a short time and maintained high rates of fermentation. The rate of fermentation for glucose, fructose, sucrose, maltose and lactose rose up gradually with the increase in time. The yeast that was used, S cerevisiae grows aerobically on a substrate containing glucose, trehalose and maltose. Other sugars like cellobiose and lactose due support optimum growth of the yeast cells. In the experiment conducted, fermentation occurred faster in galactose than the other sugars, this ndicates that galactose is the is the most favourable sugar for S. cerevasiae

Photosynthesis

From the experiments, it is deduced that photosynthesis occurs in two stages, the light-dependent and the light-independent stage. “Generally, in the first stage energy is captured and stored in the form of ATP and NADPH.” (Allen) In the second stage (light-independent stage the energy stored is used to process sugars using carbon.

Fermentation

In the fermentation process, “the electrons released by nutrients are transferred back to the molecules of nutrients that produced them.” (kamau, 133) The fermentation process is utilized by an organism to extract energy from starch. “The fermentation process results in the formation of alcohol and acids though its main purpose is the production of energy.” (Kamau, 134) Fermentation takes place mostly on starch and is carried out by yeast cells, for example, Saccaromyces cerevisiae which is a unicellular ascomycete fungus that lives on the surface of fruits and grains and survives by extracting energy from the plenty available sugars. The budding yeast utilizes the sugars for its nutrition, during the process of fermentation alcohol and acid are produced as by products.

Works cited

Allen, Williams. “Photosynthetic reaction centers” FEBS Lett 438 (1-2): 5-9.1998. Print.

Kamau, James. Biological systems 2^nd Edition. Nairobi: East African Publishers, 2002 Print.

“Light dependent and independent reactions: Photosynthesis.” Web 2010 Wikipedia.org. Web.

Nelson, David. Lehninger Principles of Biochemistry, New York: W.H. Freeman and company Publishers. 2005 Print.

By definition, photosynthesis is a process whereby light energy (of blue and red wavelength) is converted to chemical energy in the presence of CO₂ and water. This process occurs in plants and green algae which eventuate in sugar formation. Basically, the site of photosynthesis in plants is at the chloroplast which contains chlorophyll (apparently green pigment) vital in absorbing light energy.

Primarily, the chemical reaction that happens in the chlorophyll is typified by the equation: 6CO₂ + 6H₂O + light energy → C₆H₁₂O₆ + 6O₂. However, this process is more multifaceted than what meets the eye for it involves two processes: the light and dark reactions. The light reaction “happens at the thylakoid membrane, and it serves to convert light into chemical energy” (Audesirk & Byers, 2008). This energy is then passed onto central chlorophyll where photosynthesis happens to store the energy as ATP (adenosine triphosphate). The dark reaction, which happens devoid of light in the stroma, utilizes CO₂ and ATP to form sugars (glucose) in what is referred to as the Calvin Cycle (Fig. 1).

To utilize the sugars processed by plants, animals and plants alike initiate respiration processes which can either be aerobic or anaerobic as manifested in most microorganisms. However, the scope of this paper limits itself to aerobic respiration; a process whereby glucose/organic substrate is broken down in presence of oxygen to release energy, and molecules of water and CO₂. The energy is stored chemically as ATP and hence, can be used by other cells within an animal/plant. Basically, in a simplified equation the below reaction occurs:

C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + Energy

Akin to photosynthesis, respiration is a complex phenomenon that involves two processes: glycolysis which eventuates in the formation of pyruvic acid from glucose, and a process of oxidizing the product to CO₂, NADH, and H₂O (Fig. 2). Nevertheless, it is the NADH molecules that are utilized in an Electron Transport Chain, and chemiosmosis process to yield ATP molecules. Of note, this process occurs in the mitochondrion of a cell.

As typified by the two processes, each cycle is dependent on the other. As such, the plants and animals are symbiotic thus they accomplish what is known as the Carbon Cycle. To this end, the CO₂ is recycled in the system.

Anaerobic and aerobic respiration are different in that the former occurs in the absence of oxygen. Chiefly, this process is analogous to fermentation which results in the formation of either lactic acid or ethanol. To this end, there exist two types of fermentation: alcoholic (Eq. 1) and lactate (Eq. 2) fermentation. These processes are dwarfed by aerobic respiration concerning energy production. They result in the formation of two ATP molecules as opposed to 6 generated from a molecule of glucose through the aerobic process. This process is common in anoxic habitats.

C₆H₁₂O₆ -> 2CO₂ + 2CH₃-CH₂-OH (ethanol) + Energy (1)

C₆H₁₂O₆ -> 2C3H6O3 (lactic acid) + Energy (2)

The main chemical pathway of this kind of respiration is “glycolysis, which divides a molecule of the simple sugar glucose into two molecules of pyruvic acid, producing two molecules of ATP in the process” (Audesirk & Byers, 2008).

An enzyme is simply a catalyst in chemical terminology. As such, they act to speed up reactions that would have otherwise happened slowly. Principally, enzyme-substrate interaction is a stepwise cycle that follows the below steps:

• Step 1: Enzyme + substrate.
• Step 2: Enzyme-substrate complex.
• Step 3: Enzyme + product.

To regulate enzymatic reactions, enzyme inhibitors come in handy. Inhibitors would either block the bonding typified by step 1 by binding the substrate (competitive inhibitors), or they would bind on the enzyme changing its active sites lacking a perfect substrate march (noncompetitive inhibitor). Also, the enzyme’s activity could be regulated by the cell through non-covalent modifiers, “which causes a conformational change in between more and less active states of the enzyme” (Audesirk & Byers, 2008). Moreover, this can also be controlled by the cells at the level of biosynthesis.

References

Audesirk, T., & Byers, B. (2008). Biology – Life on earth with physiology (8th Ed.). San Francisco, CA: Benjamin Cummings.

Introduction

Strepto pyogenes was first introduced and narrated by Billroth on the verge of third and fourth quarters of the nineteenth century (1874). This first description came when the microorganism was detected from the infected wounds. Further work by Fehleisen resulted in isolation of organisms on cultures from perierysipelas lesions within the next decade; these organisms settled them in chains on the culture media. So, after a year Rosenbach called them for the first time as S pyogenes.

Main text

S pyogenes belong to the phylum firmicutes, class bacilli, genus streptococcus, order lactobacillus, family streptococcaceae and species s pyogenes. It is a spherical gram positive bacterium and when cultured, it grows on media in long chains. Group A streptococcal infections are caused by this microorganism. It produces group A antigen on its cell wall; it also displays beta-hemolysis when the culture medium used is blood agar. One of its unique features is large zones of hemolysis because of the complete disruption of red blood corpuscles and as a result release of hemoglobin. This microorganism is catalase-negative with an incubation period of ten days when the conditions are favorable.

Initially, different types of hemolyses were described by Brown which was followed by the Lancefield classification of beta-hemolytic streptococci by serotyping on the basis of M-protein precipitin reactions. It was at this time that the role of M protein was established in disease causation.

Different scientists including George and Dick determined that scarlet fever was the result of this microorganism.

The other two very important autoimmune diseases, acute rheumatic fever and glomerulonephritis, have also been linked to post-infectious sequelae of hemolytic streptococcal infections.

Metabolism

Like metabolic needs and their satisfaction in other microorganisms, S.pyogenes has also got various pathways and chemical reactions that maintain the metabolic needs of the microorganism. Some of these pathways or chemical reactions are given below:

Heterotrophic Metabolism

It is the biologic oxidation of organic compounds, as glucose, to produce ATP and inorganic compound. This energy-producing step is required by the microorganism to meet its demand.

Respiration

It is a type of heterotrophic metabolism in which oxidation of glucose takes place. The process results in the production of 38 moles of ATPs from 1 mole of glucose, thus yielding approximately 380,000 cal.

Fermentation

This is a process in which comparatively less amount of energy is produced. Here some organic compound replaces oxygen, in comparison to respiration; therefore, this process supports the anaerobic respiration.

Krebs Cycle

Although, this is an oxidative reaction, pyruvate instead of glucose, is the substrate to be oxidized. In this cycle 15 moles of ATP are produced.

Electron Transport and Oxidative Phosphorylation

There is a series of electron transfer reactions that takes place at the terminal stages of the respiration and eventually ATP is produced. The process occurs in the cytoplasmic membrane where the process of phosphorylation of ADP to ATP produces energy. Various types of cytochrome, flavins and cytochrome oxidases are utilized.

Bacterial Photosynthesis

It is an anaerobic mode of metabolism which needs light.

Carbon dioxide reduced to glucose which is the substrate to be used for energy production. Two types of processes, photolithotrophic and photoorganotrophic, exist in these microorganisms like others.

Autotrophy

This mode of metabolism is also known as, chemotrophic and chemoautotrophy. This is a unique type of metabolism that takes place only in bacteria. In this type, inorganic compounds are oxidized directly, excluding sunlight, to yield energy (e.g., NH3, NO2–, S2, and Fe2+).

Anaerobic Respiration

This process is similar to the respiration wherein the terminal stages oxygen acts as electron acceptors; here instead of oxygen some other compounds are utilized for this purpose, including NO3–, SO42–, fumarate, and even CO2 for methane-producing bacteria.

The Nitrogen Cycle

This cycle is actually a recycling mechanism where organic and inorganic nitrogen compounds are metabolic. This way these compounds are recycled among bacteria, plants and animals. Actually, this important type has got very important role in maintaining the nitrogen balance in the nature.

Virulence factors

S. pyogenes contains a variety of factors which help it in invading the host cells and provide facilitation in this regard.

Capsule

A carbohydrate capsule is the outermost layer which surrounds the microorganism; it is composed of hyaluronic acid. This acts as a protective layer especially providing protection from phagocytosis.

Cell Wall Proteins, M and F

Moreover, this capsule and some other factors embedded in the cell wall along with the capsule favor attachment of S. pyogenes to the host cells. These factors are M protein which is composed of lipoteichoic acid and protein F (SfbI).

M protein inhibits opsonization when it binds to host complement regulators when the alternative complement pathway is active. Being part of some serotypes, M protein also prevents opsonization by binding to fibrinogen.

Releasing Factors

In addition to the components of the microorganism which helps in the process of the invasion, some chemicals are released from S.pyogenes and contain the qualities of a virulence factor.

Some of these chemicals are described here:

Streptolysin O and S

This microorganism releases some toxins, the substances which are lethal to the host cells. Based on these toxins S. pyogenes produces beta-hemolysis. Moreover, Streptolysin O has got poisonous characteristics to those host cells which are an important component of the defence system, neutrophils and other cells. The individuals who are infected by this microorganism they react by producing antibodies as a result of an immune response. These antibodies when detected in the serum of the infected individuals help in the diagnosis of infection.

Streptolysin O has also got cardiotoxicity.

Streptococcal pyrogenic exotoxins A and C

Spe are the streptococcal pyrogenic exotoxins, SpeA and SpeC. These are secreted by a lot of strains of this microorganism and termed as the superantigens. The rash and scarlet fever are the examples of infections initiated by these exotoxins along with some of the symptoms of toxic shock syndrome.

Streptokinase

It is an enzyme which activates another proteolytic enzyme, plasminogen.

After activation this enzyme digests some proteins including fibrin which helps in waling off the infection.

Hyaluronidase

Hyaluronic acid is one of the basic components of the connective tissue and provides structure to this tissue. As the name exhibits, the above-mentioned enzyme results in the breaking down process of this connective tissue component. As this structure disrupts the spread of infection becomes easier.

But there is some paradox! There is a small number of isolates that have got the ability to produce active hyaluronidase; also the strains that have got this ability do not the spread through skin or connective tissue.

Streptodornase

DNases are the enzymes which act as the defence system as they protect bacteria from getting trapped in the webs produced by DNA.

C5apeptidase

The complement system produces C5a, a neutrophil chemotaxis. It attracts the neutrophils when an external insult especially in the form of a microorganism. This peptidase enzymatically dissolves this chemotaxis and disrupts the communication mechanism between the complement system and neutrophils.

Streptococcal chemokine protease

Severe cases of necrotizing fasciitis are deficient in neutrophils. S.pyogenes releases ScpC, a serine protease, which interrupts the movement and migration of the neutrophils towards the infection site. This takes place when chemokine IL-8 is dissolved by ScpC.

Chemokine IL-8 actually attracts neutrophils to the infected site.

Factors which make S.pyogenes vulnerable

M protein which is involved in the inhibition of opsonisation, is also the component of this microorganism which places at a greater risk. In fat, it is the characteristic that weakens S. pyogenes. The point is that whenever immune response develops against this microorganism the host produces antibodies that are targeted to the microorganism through this M protein. As this protein is unique for each strain so the response is also unique.

Control

Penicillin is the treatment of choice. It requires starting treatment at an appropriate time. If time is taken care off then the chances of developing glomerulonephritis and rheumatic fever become very low. There is no vaccine developed yet but the efforts are on the way.

Public Health

S.pyogenes produces usually airborne infections but fomites may also get involved. The high time for the respiratory and skin infection is the childhood. There are asymptomatic carriers that can also transmit infection. Acute rheumatic fever, although, in majority of the cases is developed in poor but it also has got some association through genetics.

Being the normal flora it can cause infection of the site where it resides; may result in neonatal infection as normally it is present in the vagina.

Introduction

Recent campaign all over the world in the media geared towards reducing the rates of obesity have with no doubt led to fats phobia and subsequently many people have stopped consuming meals rich in fats. The ironical twist of it all is that fats are a source of energy which is the engine of the body.Adispose tissue famously dubbed fat has the sole role of “storing ingested energy in the body” (Badman & Flier, 2007).

Fats regulation

A gross rise in the increase of weight has led to serious scientific research and debates to come up with the most efficient way to regulate the human body weight. its worth noting that the main cause of increase in obesity in recent years is as a result of numerous factors but surprisingly and mistakenly all efforts of dedicated towards reduction in consuming meals with fat contents (Badman & Flier, 2007).

Scientific research has been gathered which shows that genetic variations and environmental influences form part of fats related health issues. Studied research shows that a gene known as FTO is responsibly linked to obesity after scanning forty thousand genome wide scans. Carriers of FTO in the cases aforementioned are said to have three kilograms heavier than other people (Badman & Flier, 2007). Basically genes alone can’t bring about obesity but their interaction with environment facilitates obesity. The said environment catalyses the process

The likes and the dislikes

Bearing in mind that there other methods of reducing fats in the body, I feel much persuaded to point out that the key role of the brain in the entire fat regulatory process should at all times be put into consideration. Seeing a therapist when stressed and having enough sleep to maintain the right state of the mind while providing an environment for the effective control of the regulatory system by the brain. I like the method of reducing obesity based on the patient instructions of how to avoid certain diets, encouraging them to start physical exercises and to have minimal consumption of food. This helps the patient in the most natural way. Bariatric surgery is another method which entails removing the fatty part of the stomach to minimize the stomach. I don’t like this method since it has grievous side effects just like any other surgery. One can die during the surgery and further its not economic friendly (Powell, 2007).

Suggestions

I would suggest that unless effective drugs are discovered without gross effects, people should be advised to utilize the natural methods which are not only easy to adopt.Methods such as giving the brain favorable environment to regulate the amount of the fats in the body are highly recommended. A drug for obesity has been said that it should act through separate ways but to achieve one end (Powell, 2007).

Conclusion

In our tireless efforts to research on the drug and different ways to deal with the excess fats in the body its worth remembering the function of the brain in the regulatory process of fats in the body. Those suffering from obesity should be encouraged to try physical exercises first.

References

Badman M. K. and Flier, J. S. (2007). The Adipocyte as an Active Participant in Energy Balance and Metabolism. Gastroenterology, 132,(6), p. 2103–2115.

Powell, K (2007). The Two Faces of Fat. Nature, 447, p. 525–527.

Introduction

This paper discusses the metabolism and excretion of caffeine in the human system. Caffeine is a constituent of coffee, cocoa beans, and tea, etc. and it is used as a stimulant that affects the central nervous system. Caffeine is obtained from a plant named alkaloid and it is consumed in its purest form. Its chemical formula is 1, 3, 7 – trimethylxanthine and structure are C8 H10 N4 O2 and its molecular weight is 194.19. It belongs to the family of methylxanthines. It has physiological and pharmacological effects on the different human systems like increased heart rate, respiration, renal activity, and physical performance. It leaves its deep influence on memory, cognition, moods, and alertness.

Absorption and Distribution of Caffeine

Within 45 minutes of ingestion, 99% of caffeine is engrossed in the human system. Tea, chocolate, coffee, or soft drinks like Coke, Pepsi, etc contains caffeine and when caffeine is taken in this form then amalgamation happens all through the gastrointestinal tract, and then it gets engrossed into the water content of each cell of the body. Another way of ensuring complete and rapid absorption of caffeine is through the oral mucosa and chewing caffeinated gum and other preparations. By using these methods for rapid absorption of caffeine, the plasma cells are supposed to have a maximum concentration of caffeine within 15 to 120 minutes. The effect is very rapid if consumed on empty stomach and the absorption gets slowed down due to the presence of food especially fiber in the stomach.

As caffeine passes through the GI tract, there is no hepatic first pass so it remains in the system. It binds with the plasma proteins so is hydrophilic in nature and due to this property, it is completely absorbed into the body. Though it is lipophilic as it can exceed through the cell membranes into the cell, and due to this property it can pass through the blood-brain barrier. It is present in the cells where all the physiological effects of caffeine occur.

Metabolism and Excretion of Caffeine

Caffeine metabolism takes place in the kidneys and the process is catalyzed by the microsomal enzyme systems. The production of paraxanthine and its excretion through urine is the main way of caffeine metabolism. Dimethylxanthine, di and tri-methylallantoin, uracil derivative, and uric acid are produced after the caffeine is being metabolized.

The first step of caffeine metabolism involves the breakdown of 3 – ethyl demethylation to paraxanthine and 70 to 80% of caffeine is metabolized by cytochrome P4501A2 into paraxanthine, theophylline, and theobromine. Immediately after the consumption of caffeine, the paraxanthine and caffeine concentration increases in the body within 8 to 9 hours and it leaves minute traces of toxicology into the blood. Small intakes of caffeine keep these levels at a negligible level but regular consumption results in the increase of paraxanthine in the cells. The sudden cessation in the consumption of caffeine leads to a decrease in the level of paraxanthine and withdrawal symptoms. Paraxanthine is slowly eliminated from the system via urine which is produced in the renal system. The elimination of caffeine occurs between 1.5 to 9.5 hours. This variation in the rate of elimination may be due to individual, physiological and environmental characteristics like pregnancy, obesity, attitude, smoking, use of oral contraceptives, etc. The total clearance occurs at the rate of 0.078 L/h/kg.

Summary

Caffeine is absolutely and quickly engrossed in the body after ingestion. It is rapidly distributed due to its hydrophilic and lipophilic characteristics across the membranes including the brain. Physiologically it has a stimulating effect on the system. Regular consumption of caffeine leads to paraxanthine buildup in the cells causing tolerance and withdrawal symptoms. The pace of removal of caffeine from the body depends on physiological and surrounding environmental aspects like smoking, pregnancy, oral contraception, etc.

The article “Cerebral Metabolism is not Affected by Moderate Hyperventilation in Patients with Traumatic Brain Injury” has been written in cooperation with researchers from Italy, Switzerland, and Australia. They address the impact of moderate short-term Hyperventilation-induced hypocapnia (HV) on patients with traumatic brain injury (TBI) (Brandi et al). Zurich University Hospital provided surgical intensive care units (ICU) from May 2014 till May 2017 to implement the clinical trial.

The study targets patients with a nonpenetrating head injury who are at least 18 years old. The authors use transcranial color-coded duplex sonography (TCCD) to examine the middle cerebral artery (MCA), including peak systolic velocity and end-diastolic velocity (Brandi et al). During the trial professional physicians control elevated intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure arterial oxygen saturation (SaO2), end-tidal CO2 (etCO2), and PbrO2 indicators (Brandi et al). The study protocol implies that all parameters are collected with the help of TCCD during three periods. Altogether there are five TCCD measurements, as demonstrated in Figure 1.

Analysis of data has allowed determining the reduction of the mean flow velocity (CBVF) in MCA and an increase in the pulsatility index. Therefore the authors conclude that moderate short-term HV lowers elevated intracranial pressure (ICP) effectively as it influences CBVF velocity. Furthermore, the study shows the stability of MAP and a heart rate when moderate HV takes place. The application of two additional variables, such as PbrO2, and microdialysis illustrates possible hypoxia of tissues.

The results of the research contribute to the debate over the outcomes of HV for treating patients with TBI. Findings provide supporting evidence to the assumption that moderate HV can reduce ICP and PbrO2. However, the study has limitations related to the small sample size that hinders the generalization of the authors’ conclusions. Thus, identifying sex or age differences in vasoreactivity is not possible. Finally, changes in other brain areas are not explored because the MD and PbrO2 probes depict activities in relatively small zones.

Work cited

Brandi, Giovanni, et al. “Cerebral Metabolism is not Affected by Moderate Hyperventilation in Patients with Traumatic Brain Injury.” Critical Care, vol. 23, no. 45, 2019. Web.

Abstract

According to researches conducted by clinicians, there exist numerous medical problems impacting the most countries in the recent times. These clinicians postulated that obesity is the most common problem that is affecting children in greater part of the world. It is estimated that about 20% of the children and half of the adults are overweight and significant increment was realized in the late 1960s and early 1970s. Most federal governments and other medical agencies have stepped forward with various strategies that can combat this problem. They have advocated that people should reduce the level of sugar and fat intake to curb this prevalence. These agencies have further postulated that people should consume more of complex carbohydrate. It is noteworthy that there has been general increase in the number of obese persons in America despite the reduction in the level of fat and sugar intake suggesting that there are some dietary factors that are critical to human body regulation. Glycemic index has been considered to be one of the factors that play a critical role in regulating the body weight (Brouns, 2005)

Introduction

Early studies show that different foods have different complexities in their nature due to the fact that foods are not created equal. The diverse foods that we take have different effects to our body as they have different characteristic. The glycemic index or GI is defined as a measure of the diverse effects of the carbohydrate on the level of glucose in our body. It best describes the difference by ranking the different effects of carbohydrates on the blood glucose. The breaking down of carbohydrates during digestion process leads to release of glucose into the bloodstream. The rate at which these carbohydrates are broken down in our body systems determines the rate at which glucose is supplied into bloodstream. The more rapid the breakdown of this glucose the more rapid the glucose are released into our body system. Carbohydrates that break down slowly leads to slow release of glucose into the body system. In research to find the best food that people should take to avoid obesity, Dr. David J. Jenkins developed a concept of Glycemic Index and he stated that the more the breakdown of glucose the rapid the glucose level in our body system hence high GI and vice versa is true.

Studies conducted by Jenkins defined the glycemic index of a food as the area under two hour blood glucose response (AUC) that accompanies the ingestion of certain quantity of carbohydrate which is usually 50 g. (Brouns, 2005). The secret of long term illness that results from the level of glucose in our body system is choosing low GI carbs which produce minimum fluctuations in the level of insulin and glucose. This in turn has the effect of reducing the risks of heart diseases and diabetes that are associated with the high glucose and insulin level in our body system. Some clinicians have suggested that a lower glycemic index involves the reduction in the rate of digestion and food absorption (carbohydrates). It also clearly indicates greater removal of these foods from the liver and the periphery of the products of carbohydrates absorption. The lower glycemic is postulated to be equal to the low insulin demand which leads to reduction in the level of blood lipids.

In this measure, insulin index is of paramount importance because it measures directly the reaction of insulin to food (Roche, 2003)

Benefits of the Glycemic Index

Consumption of high GI foods is very harmful to the human health since it pushes the body to extremes. It is quite imperative to change the diet at any time to curb the issue of high level of glucose in the body. The consumption of high GI foods is detrimental especially if the subject is inactive and he or she is overweight. Having lower GI in our body systems is very advantageous as because it enhances body sensitivity to insulin when there is low GI in the body. It also reduces risks that are related to heart diseases which are very dangerous to the human life. According to Voster, lower GI aids in the reduction in the level of blood cholesterol in the body. Another important thing to note about lower GI is that individuals will be able to endure problems that affect the physical fitness of the body. In addition, lower GI helps people reduce and control weight.

Ways of switching to low GI

Clinicians suggested the best approach for switching to low GI is swapping high GI carbs for Low GI carbs. This simply done by eating low GI diet such as Increasing fruits and vegetables consumption, constant consumption of oats, barley and bran as breakfast, reducing consumption of potatoes and eating plenty of salad vegetables with a vinaigrette. The GI of a particular food is determined mainly by carbohydrate type, fiber, protein, food form and method of preparation. The belief that digestion of carbohydrate is linked to the length of the saccharide chain is very controversial as there is close relationship.

People use the glycemic index to choose the type of diet to take especially food rich in carbohydrates that will increase the level of blood sugar in the body minimally. This is mainly intended to reduce health problems that are caused by high blood sugar. These health problems may include diabetes, the insulin resistance syndrome, hypoglycemia and heart diseases. It is imperative to note that dietary glycemic index can also be utilized by athletes who are undergoing training exercise. They can choose to use high glycemic food-index food after e tedious exercise to refill exhausted carbohydrates (Roche, 2003)

Low fats versus low GI

It is imperative to understand the fact that protein intake for most individuals remains within a fairly narrow range hence reduced consumption of dietary fat leads to compensatory rise in carbohydrate consumption. The rise in carbohydrate consumption is a replacement of fat in low fat diet which is a typical high GI. About data that agricultural departments have been collecting and analyzing, about 81% of the carbohydrates that are consumed by human beings would give rise to increase in of GI as compared to table sugar. The rate at which carbohydrates are consumed increases after the ingestion of low fat meal due to the fact that fat acts to delay the process of gastric emptying. This in turn has the effect of increasing the GI hence prevalence to obesity (Roche, 2003)

Effects of GI on metabolism

Clinical studies suggest a role dietary glycemic index on body weight regulation and other risks that are associated with heart attack. High GI has been indicated to enhance adiposity in certain class of animals such as rodents. According to relevant studies conducted it has been observed there are long term metabolic effects of high and low GI. When animals take food that can be rapidly absorbed into the body system, there are high chances that the respiratory quotient of these animals is going to be high. If examination is done on two different groups of people who have taken different types of carbohydrates i.e. slowly absorbed carbohydrates and rapidly absorbed carbohydrates, with same respiratory quotient, physical activity and energy expenditure, it will be found that there are differences in metabolic process in the body system of these people. Those people who take rapidly absorbed carbohydrates grow fat as compared to those who take the slowly absorbed carbohydrates. The respiratory quotient of those who have taken rapidly absorbed carbohydrates is high which indicates clearly that the process of fat oxidation is less in comparison with those who have taken the slowly absorbed carbohydrates. If animal models are used to study these processes, the outcomes will be that GI affects body composition which is interceded by changes in substrate oxidation. Another outcome would be high GI diet leads to insulin resistance and dietary composition can impact physical activity level.

Clinicians have proved beyond doubt that consumption of higher GI diet some minutes before exercise results in the decrease of blood glucose when the body is exposed to some exercise. There is also reliance of carbohydrate as fuel during the exercise process. From this, it has been concluded that lower GI foods promotes metabolic response before exercise is initiated. When one is undergoing an exercise, it is recommendable that carbohydrates-rich items are provided to him. This is aimed at reducing the rate at which depletion of body carbohydrate which in turn delays the inception of fatigue. Consumption of high GI foods has the effect of increasing insulin and thus depressing fatty acids which are obviated upon the consumption of carbohydrate when the body is on exercise. This occurs due to the fact that exposing body to exercise induces epinephrine elevation which depresses the release of insulin from the pancreas. This was proved by clinicians such as Brouns (2005)

Effects of Dietary Glycemic Index on health and diseases

There are minimal effects experienced if a healthy young man low glycemic index diets in the short term. The dietary glycemic index suggests that ingestion of fiber leads to a decrease in the rate of nutrients from the gut. This idea is also present in the fiber hypothesis. Early clinicians have shown that some of the chronic diseases that are attributed to central obesity and insulin resistance are related to glycemic index. Dietary glycemic index has the effect of giving rise to insulin resistance. It is important to note that starchy foods affect postprandial blood glucose in different ways. The starchy carbohydrates also affect the way insulin response to subjects that are related to health and diabetes which depends entirely on the rate of digestion in the body system. Consumption of carbohydrates with high GI has the effect of altering the rate at which glucose is absorbed which might result in related diseases such as glycemia and insulinemia. It is from these effects of different starchy food that indicates there are differences in the effects of carbohydrates due to the differences in the GI level. Early studies indicate that the classification of carbohydrates is relevant in treatments and prevention of diseases such as diabetes (Vorster, 2002)

Low-glycemic-index diets are very useful because it improve the glycemic control in patients suffering from diabetes. It also reduces serum lipids among individuals who have hyperlipidemic problems. Consumption of high glycemic index diets can lead to cardiovascular diseases hence people should consume low glycemic index food to curb these problems.

Low glycemic index food is been advocated by many doctors than high glycemic index food because high glycemic index food can lead to increase in the sugar level in blood. To counterattack this phenomenon, the body produces insulin in large amount. It is with this respect that the human body cannot tolerate the high level of blood sugar and insulin that are produced rapidly by the body due to high glycemic index foods in the diet. The trend of food consumption is changing in the modern days, where people are consuming high glycemic index food such as low fiber flours and whole grains. This is due to human civilization where primitive Stone Age diets are being replaced by high glycemic index. These changes in the consumption trend where higher glycemic-index foods in the diet are mostly consumed, is very dangerous and hazardous to the normal functioning of the body. Too much production of insulin when high glycemic index food can lead to insulin resistance hence the cells that are responsible for responding to insulin become less active and cannot respond to its effects as suggested by Vorster (2002)

Dietary Glycemic index can be utilized to prevent and treat cancer. Insulin resistance is suggested to be associated with diet related cancers such as breast and prostate. There is direct link between colon and breast cancer and dietary glycemic index (Brouns, 2005). These attributes of excessive high glycemic index, insulin resistance, high levels of insulin are very daring to the human health. These have led to body disorders and health problems such as obesity, type 2 diabetes heart diseases and sometimes cancers. It is important to note that studies conducted have shown that human beings should change to low glycemic –index food. This reduces insulin resistance; it lowers blood levels and enhances blood sugar control. Advocates have constantly criticized high glycemic index food to result in serious health problems. Suggestions have been made by other advocates that diet can be more healthful if glycemic index is integrated with other health concepts (Jenkins, 1998)

Criticism of Dietary Glycemic Index

Glycemic has had a lot of criticism from various clinicians due number of reasons. Clinicians and other doctors have postulated that glycemic index does not consider variety of factors apart from glycemic response. These other factors include insulin response which is measured by the insulin index which is considered to be more appropriate in ascertaining the effects of certain carbohydrates rich items. The glycemic response is never constant as it varies depending on the kind of food, the ripeness of food and the length of time it was stored. Mode of cooking also matters. Blood glucose levels are the main determinant of GI hence this varies from person to person difficult to ascertain the efficient GI level that is necessary for human beings. Again, there is difficult in predicting the GI of meals which contains variety of food items e.g. when a meal has both protein and fats the more it stay longer in the stomach hence reduction in food GI (Vorster, 2002)

Conclusion

The various research and studies conducted concluded that concept of dietary glycemic index indicates that it has a role in the digestion process of carbohydrate. This concept is also very useful in prevention and treatment of diseases that are associated with insulin resistance. Glycoside hydrolase inhibitors is been used in management of diabetes and it is a pharmacologic approach that is accepted universally (Jenkins, 1998)

References

Brouns, G., 2005. Dietary Glycemic Index..” Nutrition Research Reviews 18; 140-174

Gibney, M. 2004. Glycemic Index and Metabolism. The Definitive Science-based Weight Loss, 20; 150-169.

Jenkins, J., 1998. Glycemic index of foods. 350-370.

Roche, H., 2003, Metabolism and Nutrition. 120-127.

Vorster, M., 2002. A Health Promotion Approach. 360-378. Nutrition Research Reviews 18; 145-17.

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Abstract

Screening for inborn metabolic errors began in the early 1970s; tandem mass spectrometry (MS-MS) is an improved technique of mass spectrometry. It has the potential of performing one test to detect many inborn metabolic errors. The question of cost-effectiveness is an obstacle to extending its use as a first-line screening tool. This essay aims to provide a brief yet comprehensive review on the use of tandem mass spectrometry in screening for inborn errors of metabolism.

Introduction

The theory of mass spectrometry (MS) is to spawn ions from a substance (organic or inorganic), separate them according to their mass-charge (m/z) ratio, and finally, quantitative and qualitative ion detection based on their m/z ratio.

The substance is called analyte and might be ionized thermally, electrically, or by the impact of high-speed electrons, protons, or ions. The resulting ions can be single, clusters or fragments of molecules. Thus, a mass spectrometer has three main parts, an ion source, a mass analyzer and a detector; all operate under high vacuum conditions (Gross 2004, p. 3).

Principle of Tandem mass spectrometry

Tandem mass spectrometry (MS-MS) is an improved technique of mass spectrometry where a four-pole (quadrupole) mass filter selects the intact ions produced from the analyte stream of ions. When the original ions stream passes through the collision cell (into which argon gas flows at a slow rate), the energy produced by collision results in fragmentation and rearrangement of the analyte stream ions to productions. Next, the productions go to a second quadrupole filter, allowing selected defined intact ions to the detector (Figure 1) (Vogeser et al, 2007).

The need for vacuum is to minimize the pressure with the spectrometer well below atmospheric pressure to prevent ions’ collision with air molecules. The basic idea of quadrupoles is through them, in a specific frequency pattern, only ions of a specified mass can pass. In the detector, ions’ analysis depends on their different accelerations, which depends in turn on their mass, in an electric field (Vogeser et al, 2007).

Inborn metabolic errors

Sir Archibald Garrod brought the term inborn error of metabolism to attention, for the first time, during his lecture at the Royal College of Physicians in London in 1908. Sir Garrod identified alkaptonuria, benign pentosuria, albinism and cystinuria as a group of diseases that appear to occur because of failure in some steps of chemical changes constituting metabolism. Sir Garrod added these disorders present at birth, continue for the rest of life, are benign in nature and show little if any response to therapy. They constitute a wide variety of diseases classified according to the metabolic pathway affected (Clarke 2005, p.1). Table 1 shows examples of inborn metabolic disorders.

Table (1) Examples of inborn metabolic disorders (adapted from Kumta 2005, p. 326).

In cases of inborn metabolic disorders, history of pregnancy and delivery is usually uneventful, and the infant may be normal for the first few hours. There are certain specific features for these disorders with abnormal urine or body odor, diarrhea, cardiomyopathy or failure, hepatomegaly and seizures are the most alarming. A characteristic feature of these disorders is although they are individually rare; yet together they form a significant morbidity to the pediatric population with disabling outcomes and even death in some cases.

The basic management strategy is to prevent the accumulation of toxic precursors, supply the defective product or essential nutrients. Therefore, early screening and prompt diagnosis of inborn errors of metabolism are significant (Kumta, 2005). The aim of this essay is to review the use of tandem mass spectrometry in screening for inborn errors of metabolism.

The use of tandem mass spectrometry in screening for inborn metabolic errors

Screening for inborn metabolic errors began in the early 1970s by assessment of phenylalanine in infants with phenylketonuria, since then technological advancement and development of advanced instruments enabled screening of many other errors. Tandem mass spectrometry is advantageous over ordinary screening methods in detecting many metabolites from one blood spot, thus allowing screening of many inborn metabolic errors simultaneously (Pasquali, 2005).

Pandor and colleagues (2004, pp. 15-25) reviewed the clinical efficacy of MS-MS in screening neonates for inborn errors of metabolism. They suggested that although tandem mass spectrometry can successfully detect many disorders; yet, the best candidates for MS-MS screening are MCAD (Medium Chain aceyl-coenzyme Dehydrogenase) deficiency causing disordered fatty acids metabolism. This co-enzyme deficiency can result in increased infant mortality and morbidity and is preventable by diet regulation. The second best candidate for MS-MS screening is for amino acids and acylcarnitines enabling early diagnosis of amino acids inborn errors of metabolism like phenylketonuria, maple syrup urine disease and tyrosinemia.

Studying acylcarnitines profiles in newborn infants identifies fatty acid oxidation defects and organic acidaemia. Pandor and colleagues (2004, pp. 15-25) emphasized this does not represent the full spectrum of using tandem mass spectrometry for screening of inborn metabolic errors and suggested future research should focus on the impact of early diagnosis on impairment and disability adverse outcomes of these disorders.

Tandem mass spectrometry: Technique and advantages

The sample needed for tandem mass spectrometry is a drop of blood (obtained by a small punch) and collected on a filter paper. Sample extraction is by methanol, and then dried; next water and acetonitrile are added to the sample, which is next injected into the tandem spectrometer. In the spectrometer, all molecules are ionized commonly by electrospray (electrical charging of the molecules), then the resulting charged ions (positive or negative) are separated according to the m/z ratio.

In the collision cell, ions’ fragmentation by collision with argon gas occurs and is then separated according to the m/z ratio. Single charged ions will have a mass-charge ratio equal to the mass of molecules ionized, further, each molecule has a specific fragmentation pattern with some compounds as acylcarnitines have a similar fragmentation pattern. This is unlike what happens to amino acids as they lose a neutral fragment of 102 mass-charge ratios after fragmentation. Therefore, tandem mass spectrometers are set up to measure metabolites according to available information about their masses and fragmentation patterns (Dettmer et al, 2007).

An advantage of tandem mass spectrometry is interpretation of results depend on fragmentation pattern and does not measure the concentration of different metabolites. Besides, the capability of detecting many metabolites allows using the metabolites ratios to identify whether an elevated value (measured by traditional screening methods) is because of a metabolic disorder or secondary to nutritional status.

Another advantage of MS-MS is clear on screening of acylcarnitines. Whereas amino acids concentrations do not change much with age, acylcarnitines concentrations do being highest at the first week then decrease rapidly afterward. Therefore, traditional methods need to set a cut-off value for acylcarnitines assessment according to age groups, which is not the case with MS-MS (Pasquali, 2005).

Tandem mass spectrometry: Current and future strategies

The current strategy of tandem mass spectrometry is to provide accurate measures of both molecular (precursor) and productions after fragmentation. Quadrupoles make this possible where scanning of precursor molecules takes place in a first mass analyzer (in space-based MS equipment, which involves physical separation of components). Next, a second experiment on selected precursor ions allowed them to fragment then scan for quantification of productions.

This strategy is known as MS^E where precursor ion selection is automatic with no human factor interference; thus, no need for new data of which metabolites are expected to be present. Further developments in quadrupoles would increase mass accuracy, sensitivity and dynamic range; thus, allowing the use of tandem mass spectrometers in the framework of a new strategy, that is more targeted and more selective analysis (selected reaction monitoring); thus allowing higher sensitivity. Another alternative is developing instruments with a single quadrupole, which will make unlimited quantification possible (Dunn, 2008).

Cost-effectiveness

Despite more than 30 inborn errors of metabolism that can be diagnosed by MS-MS; yet, its universal routine use in neonatal screening is a matter of discussion, primarily for its high cost. Schoen and colleagues (2002, p. 781) conducted a cost-benefit analysis to assess routine use of MS-MS in screening neonates for inborn errors of metabolism. They estimated the cost (adjusted per quality life-year saved by MS-MS) to range from $ 11,419 (in worst scenarios) to $ 736 (in best scenarios) with an average of $ 5872.

They assumed this high cost in newborn screening to other factors included but not concrete as the costs of personnel, training, tracking test results, parents’ counseling, supplying special diets and care. They inferred that adjusted costs compare promisingly to policy encouraged screening methods; however, whether diagnosis of these disorders is pre-symptomatic or after manifested the cost is still high.

Pandor et al, (2006, p. 321) examined cost-effectiveness of MS-MS in a different economic model. They compared the cost of tandem mass spectrometry to the cost of traditional technologies in diagnosing phenylketonuria. Then they added diagnosis of MCAD and evaluated cost-effectiveness within a UK NHS perspective. Their results suggested adding MCAD to the diagnostic battery of MS-MS produced a cost-saving accompanied by a mean incremental gain in life/years rate. Pandor colleagues (2006, P. 231) inferred the introduction of MCAD screening should result in better cost-effectiveness and a better neonatal health outcome.

Who to screen

Inborn errors of metabolism have characteristic clinical criteria, the age of onset is at early infancy and may extend to early childhood, second is the characteristic temporal disorder profile that is evolution of clinical features as the disease progresses. Third is the characteristic mode of inheritance, which is generally autosomal dominant and rarely X-linked recessive mode of inheritance like Hunter’s disease and Menkes disease. Finally, these disorders have characteristics triggers, which may be dietary (galactosemia, hereditary fructose intolerance), Infection, fasting, fever, anesthesia (homocystinuria) or drug-induced (G6 PD deficiency (Kumta, 2005).

Sharma et al, (2008, p. 272) agreed that screening for metabolic errors should begin as early as possible based on high suspicion index. They suggested a first line of investigations (metabolic screen) for all infants suspected to suffer from this metabolic error. This line comprises the following investigations; complete blood count where neutropenia and thrombocytopenia can raise suspicion of propionic and methylmalonic acidaemias, and plasma ammonia.

They also recommended estimation of arterial blood gases and electrolytes, blood glucose, arterial blood lactate, urine ketones, urine reducing substances, liver function tests, and serum uric acid. Based on results of the metabolic screen, investigation may proceed to the second line of confirmative tests (to support the diagnosis).

Second-line investigations are many and performed on targeted selective basis, these tests include gas chromatography of urine for organic acidaemia, lactate-pyruvate ratio, urinary orotic acid for urea cycle errors, and enzyme assay. They also include MRI neuroimaging for maple syrup urine disease (brainstem and cerebellar edema), propionic and methylmalonic acidaemias (basal ganglia signal change). In addition, EEG may help to point to some metabolic errors as holocarboxylase synthetase deficiency (Sharma et al, 2008).

The current place of Tand2em screening

Tandem mass spectrometry is used for neonatal screening (first or second line) variably in many countries. It can diagnose amino acids inborn metabolic disorders (as phenylketonuria), fatty acids oxidation defects, and organic acidaemia (Jilkhani et al, 2008).

Conclusion

Tandem mass spectrometry is a technological advancement that can diagnose a variety of inborn errors of metabolism and has the potential for expanding neonatal screening for these disorders. Its main advantage is pre-symptomatic of these disorders enabling early management, however, proper interpretation of results needs training and familiarity with these disorders. The technique is promising one test to diagnose many disorders and can have a favorable impact on the health of infants with inborn metabolic disorders and their families.

References

Clarke, J TR, 2005. A Clinical Guide to Inherited Metabolic Diseases. Third edition. Cambridge, UK: Cambridge University Press.

Dettmer, KA, Aronov, PA., and Hammock, B, 2007. Mass Spectrometry-Based Metabolomics. Mass Spec Rev, (26), 51-78.

Dunn, W, 2008. Current trends and future requirements for the mass spectrometric investigation of microbial, mammalian and plant metabolomes. Phys. Biol, (5), 1-24.

Gross, J. H., 2004. Mass Spectrometry: A Textbook. Heidelberg, Germany: Springer-Verlag.

Jailkhani, R, Ptail, VS, Laxman, HB, Shivashankara, AR, et al,, 2008. Selective screening for inborn errors of metabolism in children: Single center experience from Karnataka. Journal of Clinical and Diagnostic Research, (4), 952-958.

Kumta, N. B., 2005. Inborn Errors of Metabolism (IEM)-An Indian Perspective. Indian Journal of Pediatrics, (72), 325-332.

Schoen, EJ, Baker, JC, Colby, CJ, and To, TT, 2002. Cost-Benefit Analysis of Universal Tandem Mass Spectrometry for Newborn Screening. Pediatrics, 110(4), 781-786

Pandor,A, Eastham, J, Beverley, C. Chilcott, J, and Paisley, S, 2004. Clinical effectiveness and cost effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review. Health Technol Assess, 8(12), 1-144.

Pandor,A, Eastham, J, Beverley, C. Chilcott, J, and Paisley, S, et al, 2006. Economics of tandem mass spectrometry screening of neonatal inherited disorders. International Journal of Technology Assessment in Health Care, 22(3), 321-326.

Pasquali, M, 2005. Tandem Mass Spectrometry: Principles and Interpretation of Results. Genetic Drift, 7-9.

Sharma, S, Kumar, P, Agarwal, R, Kabra, M, et al,, 2008. Approach to Inborn Errors of Metabolism Presenting in the Neonate. Indian J pediatr, 75(3), 271-276.

Vogeser, M., Kobold, U. and Seidel, D., 2007. Mass Spectrometry in Medicine – the Role of Molecular Analyses. Dtsch Arztebl, (104), A2194-2200.