Why do we treat amino acids the way we do, and what issues do they raise in our body:

  1. Despite being essential building blocks for our enzymes, proteins, movement, etc, we are not able to synthesise them all in our body, so many of them are essential in our diets in order to survive

  • So we need to have a mechanism to convert them from one type into another to create those that we need and that we may have not gotten enough of in our diet

  1. We cannot store them, so we need to continuously have them in our diet, keep a pool of all the 20 types we need available in our blood for our cells to take up as needed (via specific Na+ coupled channels)

  • Also because we cannot store them, if we have too many, we need a mechanism to convert them into some other form of molecule (carbohydrate, fat) so they can be removed from the bloodstream

  • Amino acids have an amino group, so we need a way to get rid of the nitrogen when we convert an amino acid into another molecule (carbohydrate, fat) and because ammonia is highly reactive and toxic to the brain, this mechanism needs to be very efficient

Explain the concept of protein turnover, dynamic equilibrium, and amino acid pools

We have a continuous need for protein because a lot of cells themselves are short lived, in growth we need to make more cells, peptide hormones are short lived – so we have a constant protein turnover in the body, which creates a constant need for amino acids. This is provided in the form of an amino acid pool, which is all the free amino acids located inside cells or in the bloodstream. Because the amino acids from the gut into the blood depend on the type of food we eat, the type and amount of amino acids always changes, so the body has to try and keep all 20 types available through synthesis of those which are needed: transamination.

Explain how amino acids are classified as essential or nonessential and the significance of this classification

Which are essential: Valine, Methionine, (Histidine), Lysine, Phenylalanine, Leucine, Isoleucine, Threonine, Tryptophan, (Arginine). Mnemonic: Very many hairy large pigs lived in the thick Argentine. Any one with a weird structure that you wouldn’t find in any of the metabolic pathways basically, needs to be taken in the diet. It’s important to know, so that we ensure that we get these from our diet.

Why don’t obese people live for much much longer during starvation? Even though they do have more fat, so they can release more energy, if they aren’t getting protein in their body, the won’t be able to synthesise amino acids, so the lack of these will cause them to die.

A lot of the amino acids are taken from proteins already broken down in our body – which will give us quite a rich variety of amino acids. Eating animal protein also gives a rich variety of proteins, if you eat vegetables, pulses, grains, you will need to combine them in different ratios to obtain the variety you need.

Explain the concept of nitrogen balance and the causes of positive and negative nitrogen balance

There should be a balance between the amount of nitrogen taken in the diet in the form of protein and the amount of nitrogen excreted from the body in the form of urea, uric acid, creatinine and NH4+. Positive nitrogen balance: more intake than excretion – growth, moving after immobilization, pregnancy Negative nitrogen balance: more excretion than intake – starvation, late stages of cancers, injury or trauma (surgery included) This is always dynamic: because you can’t store protein, if anything major happens to the body you will end up going back and forth between negative and positive nitrogen balance.

Outline the pathways of protein degradation Explain the terms transamination, deamination and transdeamination Describe the action and significance of aminotransferase enzymes

The source of amino acids:

  1. Proteins already in our body are taken into vesicles by endocytosis or autophagocytosis, fuse with lysosomes, and proteolytic enzymes there degrade them into amino acids

  2. Amino acids taken in the diet

Why are amino acids broken down:

  1. To form amino acids that are needed but aren’t in the pool = transamination

  2. To get rid of excess amino acids by removing the amino group and converting them into other molecules (they cannot be stored) – transdeamination and deamination

Amino acids themselves are broken down into NH2 and oxo/keto acids – this is the first step in transamination. (importantly, B-vitamins are required as coenzymes in these processes, the enzymes are aminotransferases). The NH2 group can therefore be transferred to another keto acid (which is an intermediate of another metabolic pathway) and convert that keto group into a new amino acid – this is what aminotransferases do.

Aminotransferase – catalyses the transfer of an a-amino group from the a-amino acid to the a-keto acid.

To fully deaminate you need to transdeaminate. The only amino acid capable of being deaminated as the last step (what is required to lower the amount of amino acids in circulation) is glutamate, which can transfer its N part of the amino acid to an acceptor molecule. NH2 group is transferred into ammonia NH3 or NH4+ and is toxic to the brain, so it needs to be removed fast from the body, it is immediately converted into urea – in the liver during the urea cycle. The urea is then transported to the kidney which removes it from the body.

The urea cycle Takes NH4+ and carbon dioxide and ATP, using Aspartate, forms fumarate and urea.

Explain the importance of glutamate, glutamine, aspartate and alanine in amino acid metabolism

What is a keto acid? An amino acid without its amino group. Its fate is either: 1. Becomes another amino acid by transamination 2. Be metabolised by the TCA pathway to carbon dioxide and water and ATP 3. In the cases of starvation, it can be converted to glucose in the liver – a glucogenic keto acid – phenylalanine,, tyrosine. Tryptophan, isoleucine, threonine

Muscle and liver Most amino acid degradation happens in tissues other than the liver (for example muscles in exercising and fasting), so those tissues also form nitrogen. Because they don’t have urea cycle enzymes – so how do they get this urea to the liver?

Alanine cycle (like Cori cycle – lactic acid from muscles is converted back into pyruvate in the liver) in the alanine cycle, nitrogen is added to pyruvate to form alanine, which can then be released into the blood. The liver converts alanine back into pyruvate by transamination. (the pyruvate can be used for gluconeogenesis and the amino group for urea).

Glutamine – glutamate and NH4+ are converted into glutamine by glutamine synthase and its nitrogens can be converted into urea in the liver.

In the image: ALT-alanine transaminase. Glucose gets converted into pyruvate that can undergo transamination into alanine.

How is urea formed? It is essentially a condensation of free ammonium ions (from glutaminase and glutamate dehydrogenase reactions) with bicarbonate.

Most of the NH4+ formed by deamination of amino acids in the liver is converted to urea, and the urea is excreted in the urine. he NH4+ forms carbamoyl phosphate, and in the mitochondria it is transferred to ornithine, forming citrulline. he enzyme involved is ornithine carbamoyltransferase. Citrulline is converted to arginine, ater which urea is split of and ornithine is regenerated.

Liver and kindey The liver forms urea from the excess amino acids and transports them to the kidney.