Amino acid deamination

Classification and general rule

According to the general rule, almost all amino acids undergo deamination, with the exception of lysine (Lys) and proline (Pro). Unlike transamination, where the amino group is simply transferred to another molecule and the total number of amino acids is preserved, deamination irreversibly reduces it, since nitrogen is split off as free ammonia ($NH_3$).

Three basic types of reactions are distinguished:

1. Oxidative — the main pathway, characteristic primarily of glutamate (Glu).
2. Non-oxidative — specific to amino acids with hydroxyl groups (serine, threonine) and an imidazole ring (histidine).
3. Indirect (transdeamination) — a universal mechanism for the vast majority of other amino acids.

Direct deamination: oxidative and non-oxidative

Oxidative deamination occurs mainly in the liver mitochondria. The key substrate here is glutamate. The reaction is catalyzed by the enzyme glutamate dehydrogenase with the mandatory participation of the coenzyme $NAD^+$ (sometimes $NADP^+$), which acts as a hydrogen acceptor. The mechanism includes dehydrogenation with the formation of an intermediate imino acid, followed by hydrolysis with the release of ammonia. Reaction outcome: formation of $\alpha$-ketoglutarate, $NH_3$, and $NADH$.

Alanine (Ala) can also be oxidized directly by L-amino acid oxidase (with FAD or FMN), but this pathway has low activity — alanine is usually first converted into glutamate.

Non-oxidative deamination proceeds without oxygen:

• Dehydration of serine and threonine: The enzymes serine dehydratase and threonine dehydratase use pyridoxal phosphate (PLP) as a coenzyme. First, a water molecule is split off, followed by spontaneous rearrangement and hydration. Serine is converted into pyruvate, and threonine into $\alpha$-ketobutyrate (with the release of $NH_3$).
• Intramolecular deamination of histidine: The enzyme histidase cleaves the C-N bond in the side chain without the initial participation of water. This results in the formation of urocanic acid (containing a double bond) and ammonia.

Indirect deamination (transdeamination)

Since direct removal of ammonia from most amino acids is difficult, the body uses a detour two-stage pathway. The central molecules in it are $\alpha$-ketoglutarate and glutamate.

Stage A: Transamination (in the cytosol) The amino group is transferred from the source amino acid to $\alpha$-ketoglutarate. The reaction is catalyzed by the enzyme aminotransferase, and PLP (a derivative of vitamin $B_6$) acts as the coenzyme. The essence of the stage: amino groups of various acids are "collected" within a single molecule — glutamate.

Stage B: Oxidative deamination (in the mitochondria) The synthesized glutamate undergoes the reaction described above. Glutamate dehydrogenase, with the participation of $NAD^+$ (a derivative of vitamin $PP$), splits off ammonia. As a result, $\alpha$-ketoglutarate is regenerated, which can participate in the first stage again.

IMP-AMP cycle and process regulation

In muscle tissue and the brain, the enzyme glutamate dehydrogenase has low activity. There, indirect non-oxidative deamination operates with the participation of the IMP-AMP cycle.

Sequence of reactions:

1. Through two stages of transamination, the amino group is transferred first to glutamate, and from it to aspartate.
2. Aspartate transfers nitrogen to inosine monophosphate (IMP), forming adenosine monophosphate (AMP) and fumarate.
3. AMP undergoes hydrolytic deamination: water is added, free $NH_3$ is released, and IMP is restored.

Regulation of catabolism The processes of deamination and amino acid breakdown sharply accelerate in three cases:

• During starvation (tissue proteins are broken down to cover energy costs).
• Against the background of a protein diet (excess amino acids cannot be stored for future use and undergo catabolism).
• In severe pathologies (e.g., cachexia in prolonged diseases or diabetes mellitus accompanied by massive breakdown of muscle proteins).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of ammonia neutralization in the body (ornithine cycle)
• Detailed chemical mechanism of the IMP-AMP cycle in muscle tissue
• The role of pyridoxal phosphate (vitamin B6) in amino acid metabolism reactions
• The fate of nitrogen-free residues (alpha-keto acids) after deamination
• The effect of diabetes mellitus on tissue protein catabolism

Other topics in the "Amino acid metabolism" section

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