Classification and General Rule
As a 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 remains constant, deamination irreversibly decreases their number because nitrogen is cleaved off as free ammonia ($NH_3$).
There are three basic types of reactions:
- Oxidative — the primary pathway, characteristic mainly of glutamate (Glu).
- Non-oxidative — specific to amino acids containing hydroxyl groups (serine, threonine) and an imidazole ring (histidine).
- Indirect (transdeamination) — a universal mechanism for the vast majority of other amino acids.
Direct Deamination: Oxidative and Non-Oxidative
Oxidative deamination occurs primarily in the liver mitochondria. The key substrate here is glutamate. The reaction is catalyzed by glutamate dehydrogenase with the obligatory participation of the $NAD^+$ coenzyme (sometimes $NADP^+$), which acts as a hydrogen acceptor. The mechanism involves dehydrogenation to form an intermediate imino acid, followed by hydrolysis with the release of ammonia. The end products are $\alpha$-ketoglutarate, $NH_3$, and $NADH$.
Alanine (Ala) can also be directly oxidized by L-amino acid oxidase (using FAD or FMN), but this pathway has low activity — alanine is usually first converted to 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 yields urocanic acid (containing a double bond) and ammonia.
Indirect Deamination (Transdeamination)
Because direct ammonia cleavage from most amino acids is difficult, the body utilizes an alternative two-step pathway. The central molecules in this process 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 aminotransferase, with PLP (a vitamin $B_6$ derivative) serving as the coenzyme. The essence of this step is that amino groups from various acids are "collected" within a single molecule of glutamate.
Stage B: Oxidative deamination (in the mitochondria) The synthesized glutamate undergoes the reaction described above. Glutamate dehydrogenase, with the participation of $NAD^+$ (a vitamin $PP$ derivative), releases ammonia. This regenerates $\alpha$-ketoglutarate, which can re-enter the first stage.
IMP-AMP Cycle and Process Regulation
In muscle tissue and the brain, glutamate dehydrogenase activity is low. Instead, indirect non-oxidative deamination takes place via the IMP-AMP cycle.
Sequence of reactions:
- Through two transamination steps, the amino group is transferred first to glutamate, and then from glutamate to aspartate.
- Aspartate transfers its nitrogen to inosine monophosphate (IMP), forming adenosine monophosphate (AMP) and fumarate.
- AMP undergoes hydrolytic deamination: water is added, free $NH_3$ is released, and IMP is regenerated.
Regulation of Catabolism Deamination and amino acid breakdown processes are sharply accelerated under three conditions:
- Starvation (tissue proteins are broken down to meet energy demands).
- High-protein diet (excess amino acids cannot be stored and must undergo catabolism).
- Severe pathology (e.g., cachexia in chronic diseases or diabetes mellitus accompanied by massive degradation of muscle proteins).