Protein and amino acid metabolism

1. Nitrogen
2. Amino Acids
3. Modification of Amino Acids
4. Urea and the Urea Cycle
5. Enzyme Deficiency
6. Quiz

• Nitrogen is an important molecule in the body, used in DNA/RNA and neurotransmitter synthesis. The relationship between nitrogen entering the body and nitrogen leaving the body is called the nitrogen balance.
• Amino acids can have many functions, and are made up of three classes: glucogenic (can form glucose), ketogenic (can form ketone bodies) or both. To be used as a source of energy, amino acids must undergo either transamination or deamination to create a usable carbon skeleton, which can then be used in respiration.
• Urea is an important waste molecule in the body, and is produced from protein metabolism; it relates to refeeding syndrome.
• Homocystinuria and phenylketonuria are important diseases relating to defects in amino acid metabolism.

Nitrogen

Nitrogen is an important molecule within the body. It is used in DNA/RNA, neurotransmitters, and hormones. Therefore humans need a constant supply. The main source of nitrogen is supplied by protein in the diet as they are broken down into amino acids and then absorbed at the intestinal wall.

Nitrogen in the body is referred to as ‘balanced’, which defines the relationship between nitrogen entering the body (through diet) and nitrogen leaving the body (through loss of skin and waste).

Nitrogen balance can be:

• In equilibrium, intake = loss. This is a normal nitrogen balance.
• In a positive nitrogen balance: intake > loss. This occurs in growth and pregnancy as more protein is required for growth.
• In a negative nitrogen balance: intake < loss. This occurs with trauma, malnutrition, or infection, and can also be seen during short-term fasting or with ageing.

In addition to being used in protein synthesis, amino acids can have special functions of their own. For example, glycine and glutamate are both amino acids and important neurotransmitters.

• Tyrosine - production of noradrenaline and melanin which is the pigment formed by melanocytes in the skin.
• Cysteine - glutathione production, which is important for “mopping up” any free radical species that could go on to cause cell damage.
• Tryptophan - producing serotonin, which is an important neurotransmitter in the brain.
• Histidine - producing histamine, an important chemical involved in the inflammatory process.
• Glutamate - production of GABA, which is an inhibitory neurotransmitter in the brain.
• Glycine - production of haem and collagen used to make haemoglobin, and purines used in DNA/RNA replication.

• Glucogenic amino acids can be converted to glucose through gluconeogenesis, e.g. Alanine, Aspartate.
• Ketogenic amino acids can be converted into Acetyl CoA (a precursor of ketone bodies that can be used in respiration), e.g. Lysine, Leucine.
• Amino acids can also be both ketogenic and glucogenic, meaning they can be converted to glucose or ketone bodies, e.g. Threonine, Tyrosine, Tryptophan.

• Glucogenic begins with A - Alanine and Aspartate
• Ketogenic begins with L - Lysine and Leucine
• Those in both classes begin with T - Threonine, Tyrosine, Tryptophan

Unfortunately, not all amino acids fit this pattern, such as phenylalanine which is ketogenic (important, see later).

• Insulin ("the hormone of plenty") increases protein synthesis and decreases amino acid release. This is because high concentrations of insulin indicate that there is lots of glucose available in the blood, so no gluconeogenesis is needed. Growth hormone also exhibits similar effects to insulin.
• Glucocorticoids (like cortisol) increase amino acid release for gluconeogenesis and decrease protein synthesis. This is because high levels of cortisol indicate that more glucose is needed in the blood. This relates to Cushing’s Syndrome, where excess cortisol causes excessive protein breakdown, causing characteristic thin skin and purple abdominal striae.

Modification of Amino Acids

To be used in the production of energy, amino acids have to have their amino group removed so that only carbon skeletons remain. This can be done in two ways:

Transamination is the process that swaps the amino group (NH2) on an amino acid for a carboxyl group (C=O). This can be done through two enzymes called alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Both of these reactions are reversible, meaning they can be used to produce amino acids (alanine or aspartate from glutamate) or substrates for energy production (pyruvate or oxaloacetate).

• ALT catalyses the movement of the amino group from alanine to alpha-ketoglutarate, producing pyruvate and glutamate.
• AST catalyses the movement of the amino group from aspartate to alpha-ketoglutarate, producing oxaloacetate and glutamate.

The second method of producing energy from amino acid metabolism is through deamination. This involves the liberation of the amino group as free ammonia, which is eventually turned into urea through the urea cycle.