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Metabolism
Written by Tim Sheppard MBBS BSc. Last updated 9/11/10

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What is metabolism?

If only it were simple enough to throw into a couple of words! For anyone who's had to study it, you'll know that it is made up of many complicated reactions - which, hopefully, have been displayed in a simple and clear format in this section.

Metabolism could be described as all the chemical and physical reactions that take place in order to maintain growth and normal functioning. It includes anabolism (building up molecules required by the body from nutrients manufactured elsewhere or digested) and catabolism (breaking down molecules in order to obtain energy).

In terms of catabolism, there are three important processes which the body goes through in order to breakdown glucose and fat from the body. Glucose, obtained from the diet as glucose or in the form of other sugars and carbohydrates, is broken down to pyruvate through the process of glycolysis, and when pyruvate is converted into acetyl CoA, this enters the tricarboxylic acid cycle (TCA cycle).

Fats are found in the diet generally as triacylglycerol which is broken down into its 3 fatty acids. Each of these is converted into a fatty acyl CoA molecule which enters the beta oxidation cycle to produce pyruvate. This can then enter the TCA cycle in the same way as before.

These processes produce chemicals known as NADH (from NAD+) and FADH2 (from FAD), which enter into a process known as oxidative phosphorylation to produce the all important chemical, adenosine triphosphate.

ATP, being so essential, can be derived from various different processes. Those listed above and described in this section are very important, and form the majority of energy-generating reactions, but it's worth remembering that in hunger and starvation, the body employs some excellently designed back-up mechanisms. While essential to normal functioning, the body is not solely limited to this narrow range of activities.


What is ATP?

The whole reason for breaking down all these chemicals isn't simply for the fun of it. Rather, it is to get energy. Once you've made the energy, though, how do you store it? You might make it in one part of the cell, but need it in a completely different part. For this reason, an incredibly clever system has been devised. Bonds are used as a store of energy. It requires energy to break bonds, but conversely energy is released when bonds are made. Because of all the energy involved in bond formation and breaking, some bonds will be a particularly good way of 'storing' energy.

It just so happens that adenosine triphosphate (ATP) is a brilliant store of energy. It contains particular bonds called phosphoanhydride bonds between each phosphate group which are high energy bonds, which means they store more energy than, say, the bond between a carbon and a hydrogen atom. In fact, hydrolysis of each of the phosphoanhydride bonds in ATP has a standard of around -7300 cal/mol. This means that it is very, very favourable indeed, and can help out any reactions which are not favourable - so throughout the processes of metabolism, the reactions are set out to try to produce molecules of ATP.

In many areas on this site, the stars are used as symbols of adenine triphosphate and its relatives. In order to get the energy out of a bond in ATP, it is broken down - either to ADP or AMP. ADP is adenine diphosphate - the same as ATP, but with one less phosphate group. This means that one of the phosphate groups has been broken off, and the energy in the bond which has been broken has been used for something else. If ATP is broken down into AMP (adenine monosphosphate), this means that two of the phosphate groups have been lost - so the energy from two of the bonds has been released.

In order to make the ATP molecules for this to happen, a phosphate group has to be added to ADP, or two added to AMP. Because this is the opposite to breaking one off, it means that it requires energy. Therefore when glucose or fatty acids are broken down, if a reaction releases energy, then it is stored by converting ADP or AMP into ATP. The number of ATP molecules produced gives a good indication of how efficient a fuel is, but doesn't always tell us how well it is metabolised (used in the body).

Sometimes breaking up a chemical requires a couple of ATP molecules as well as producing them. If you want to work out the total number of ATP molecules produced by breaking something down, it is best to take away the number that had to be used up in the process. For example, when glucose goes through glycolysis, it produces 4 molecules of ATP. However, it uses 2 at the start, so in actual fact, the net product is two molecules of ATP.

So, all in all a complicated topic - but put simply, breaking down chemicals in metabolism is designed to produce ATP, because, in a sense, ATP can take energy to where it's needed within the cell.


What is CoA?

CoA is the abbreviation used for coenzyme A and basically comes from the fact that it is a coenzyme and involves the organic base adenine. Not too difficult, hopefully! It is considered a 'coenzyme' because the reactions involved in metabolism have their own enzymes, but CoA is a really important part of those reactions. It is sometimes considered as a handle, as it helps other things to 'hold on' to molecules. Generally it helps with functionality, and is very important.

Coenzyme A is made from vitamin B5 which is also known as pantothenic acid. A series of reactions take place to convert the acid into CoA, which enables it to be used in the various cells of the body. It is then used to metabolise carbohydrates and fats, in order to store energy in the form of ATP.

All in all that's just a complicated way of saying that CoA is just a useful chemical that is used a fair amount!

Like ATP, CoA is made up of an adenine base, combined with a ribose sugar, to which three phosphate groups are attached. However, instead of having three phosphates in a row, one is added to the third carbon instead of the fifth. This leaves the second phosphate group open have something else bonded to it. It has a rather complicated structure, but importantly ends with a sulphur atom attached to a hydrgen atom. This is why the simplified symbol to represent Coenzyme A in a lot of this website shows an oblong reading 'CoA', and sulphur and hydrogen sticking off the end.


What is NAD+?

Like CoA, NAD+ is a very important coenzyme involved in various metabolic processes. It stands for nicotinamide adenine dinucleotide, and as the name suggests, it looks a bit like two RNA nucleotides thrown together. It has a positive charge, which makes it ideal for what it does...

A lot of the metabolic processes which occur require the removal of hydrogen - these reactions often involve a dehydrogenase enyzme. NAD+ is often used to remove this hydrogen. As it has a positive charge on the nitrogen, adding any old hydrogen wouldn't really help matters.

However, NAD+ gains a hydrogen atom in the form of a hydride ion. This means instead of a neutral hydrogen atom, or a hydrogen atom which has lost its electron (gaining a positive charge), a hydride ion is a hydrogen atom which has gained an electron - it is a negative hydrogen ion, H-. By adding this to the NAD+, the group containing nitrogen becomes neutral, forming NADH.

On this website, the molecule is often simplified because giving the whole arrangement would be far too complicated!

NAD is found in the vitamin niacin, otherwise known as Vitamin B3. The scientific name for this vitamin is nicotinic acid, and it is a part of both NAD and NADP (nicotinamide adenine dinucleotide phosphate), known as coenzyme I and coenzyme II respectively. They both perform similar functions, and are essential in removing hydrogen in various processes around the body.


What is FAD?

Like NAD+, FAD is a very important coenzyme involved in removing the hydrogen atoms from molecules in various metabolic processes. It stands for flavin adenine dinucleotide, and as the name suggests, it looks like it contains a nucleotide . It has two nitrogen atoms that are double bonded, each to carbon atoms, which makes it ideal for what it does...

As mentioned previously, a lot of metabolic processes using dehydrogenase enzymes involve removing hydrogen atoms. Although NAD+ is often used to remove these hydrogen atoms, FAD can also be used - and is in fact used most of the time when a double bond is being made.

The double bonded nitrogen atoms in FAD are particularly vulnerable, which is why FAD will grab two hydrogen atoms from the molecule it is taking them from - this turns FAD into FADH2. Since it takes two hydrogen atoms, a double bond can be formed in the molecule it has taken them from. The other advantage of using FAD is that it can take normal hydrogens - it doesn't just take hydride ions.

On this website, the molecule is often simplified because giving the whole arrangement would be far too complicated!

FAD is found in the vitamin riboflavin, otherwise known as Vitamin B2. Riboflavin is also used to form FMN (flavin mononucleotide) which performs a similar role to FAD. Although FAD, FMN, NAD+ and NADP+ are all involved in removing hydrogen from molecules, they are all essential as they are used by the body in different circumstances; therefore they perform an essential function and are each very important!!


Further Reading