To oxidize an amino acid, the cell must first dispose of its nitrogen. The -NH2 is removed via transamination (shuttled to glutamate) or oxidative deamination (released as ammonia). The remaining carbon skeleton (alpha-keto acid) can enter central metabolism.
The “central metabolism” it enters is always the familiar pipeline: pyruvate or a TCA cycle intermediate or acetyl-CoA. From there, the amino acid’s carbons are oxidized in the TCA cycle (citric acid cycle / Krebs cycle), the resulting NADH and FADH2 feed the electron transport chain, and ATP is made. Exactly the same downstream flow as glucose or fatty acid oxidation - amino acids just enter at different points. Nitrogen is handled separately by the urea cycle (next section) because free ammonia is toxic.
Transamination. An amino acid transfers its -NH2 to alpha-ketoglutarate, producing glutamate and a new alpha-keto acid. PLP (vitamin B6) is the cofactor. Credit: Wikimedia Commons, CC BY-SA
Transamination
The amino group is moved from an amino acid to alpha-ketoglutarate, forming glutamate. The original amino acid becomes an alpha-keto acid. The enzyme family is aminotransferases (or transaminases), and all require pyridoxal phosphate (PLP), the active form of vitamin B6.
Amino acid + α-KG⇌α-keto acid + Glutamate
Two clinically famous aminotransferases:
ALT (alanine aminotransferase): alanine ↔ pyruvate. High in liver. Released in liver damage.
AST (aspartate aminotransferase): aspartate ↔ oxaloacetate. High in liver, heart, muscle. Less liver-specific than ALT.
Oxidative Deamination
Once nitrogen is collected onto glutamate, it can be released as free ammonia by glutamate dehydrogenase in liver mitochondria:
Glutamate + NAD(P)+→α-KG + NH4++NAD(P)H
The ammonia enters the urea cycle (next section) for conversion to urea, which the kidney excretes.
Why Glutamate Is the Nitrogen Hub
Most amino acids transaminate onto alpha-KG (producing glutamate). Glutamate is the single molecule that collects all the nitrogen, so oxidative deamination at just one enzyme (glutamate dehydrogenase) releases free NH3 - and feeds the urea cycle. Simple, elegant architecture.
What is the common acceptor of the amino group in transamination reactions, and what cofactor do all aminotransferases require?
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Alpha-ketoglutarate is the universal amino group acceptor, producing glutamate. All aminotransferases require pyridoxal phosphate (PLP), the active form of vitamin B6. PLP forms a Schiff base intermediate with the amino acid to facilitate amino group transfer. B6 deficiency impairs all transamination.
What enzyme performs oxidative deamination of glutamate, and what does it produce?
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Glutamate dehydrogenase (GDH). It converts glutamate + NAD(P)+ → alpha-ketoglutarate + NH4+ + NAD(P)H. The ammonia enters the urea cycle in hepatocytes. GDH uniquely uses either NAD+ or NADP+ and is allosterically regulated by ATP (inhibits) and ADP (activates).
Why is glutamate the nitrogen hub of amino acid catabolism?
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Most amino acids use alpha-ketoglutarate as their transamination partner, converting it to glutamate. The nitrogen from many different amino acids thus collects on a single carrier, glutamate. One enzyme (glutamate dehydrogenase) can then oxidatively deaminate glutamate to release ammonia for the urea cycle. Glutamate is the funnel that simplifies nitrogen disposal.
