01 / 21
N

Transamination &
Amino Group Transfer (PLP)

Discover how pyridoxal phosphate powers the reversible shuttle of amino groups between molecules: the cornerstone of amino acid metabolism.

Biochemistry

What Is Transamination?

Transamination is the reversible transfer of an \(\alpha\)-amino group from an amino acid to an \(\alpha\)-keto acid. The donor amino acid becomes a keto acid, and the acceptor keto acid becomes an amino acid.

Why Transamination Matters

★ Amino Acid Synthesis
Cells build non-essential amino acids from available keto acid skeletons via transamination.
★ Nitrogen Funneling
Amino groups are funneled into glutamate, the central collector before urea cycle entry.
★ Carbon Recycling
The resulting keto acid carbon skeletons feed into the TCA cycle or gluconeogenesis.

Meet the Coenzyme: PLP

Pyridoxal 5'-phosphate (PLP) is the active form of vitamin \(\text{B}_6\). It is the most versatile coenzyme in amino acid metabolism, participating in transamination, decarboxylation, and racemization reactions.

N
\(\text{CHO}\)
\(\text{OPO}_3^{2-}\)
\(\text{OH}\)
\(\text{CH}_3\)
 Pyridoxal 5'-Phosphate
(PLP: active form of \(\text{B}_6\))
 Aldehyde: forms Schiff base with enzyme

The Core Reaction

Amino Acid (e.g. Alanine) +
\(\alpha\)-Keto Acid
(e.g. \(\alpha\)-Ketoglutarate)
 Aminotransferase (PLP)
New \(\alpha\)-Keto Acid
 (Pyruvate) + New Amino Acid (Glutamate)
\(\text{NH}_2\) transfer

Ping-Pong Mechanism

Amino Acid\(_1\)
 E-PLP (internal aldimine)
Keto Acid\(_1\)
 E-PMP (pyridoxamine form)
Keto Acid\(_2\)
Amino Acid\(_2\)
 Half-reaction 1 Half-reaction 2
\(\text{NH}_2\) stored
 on PMP

Schiff Base Intermediates

1
Internal aldimine: PLP's aldehyde forms a Schiff base with Lys residue of the enzyme \((\text{E-PLP = Lys-N=CH-PLP})\).
2
Transaldimination: The incoming amino acid's \(\alpha\text{-NH}_2\) displaces Lys, forming an external aldimine \((\text{AA-N=CH-PLP})\).
3
Ketimine: A proton shift converts the external aldimine to a ketimine intermediate.
4
Hydrolysis: Water cleaves the ketimine, releasing the keto acid product and leaving the enzyme as E-PMP.

Major Aminotransferases

ALT (GPT)
Alanine aminotransferase: transfers \(\text{NH}_2\) from alanine to \(\alpha\)-ketoglutarate, yielding pyruvate + glutamate. Liver-specific marker.
AST (GOT)
Aspartate aminotransferase: transfers \(\text{NH}_2\) from aspartate to \(\alpha\)-ketoglutarate, yielding oxaloacetate + glutamate. Heart & liver marker.

Transamination vs Oxidative Deamination

Transamination Oxidative Deamination
Product New amino acid + new keto acid \(\text{NH}_4^+\) + keto acid
Nitrogen fate Transferred to another carbon skeleton Released as free \(\text{NH}_4^+\)
Coenzyme PLP (vitamin \(\text{B}_6\)) \(\text{NAD}^+ / \text{NADP}^+\)
Key enzyme Aminotransferases (ALT, AST) Glutamate dehydrogenase
Reversibility Freely reversible Reversible (bidirectional)
Net N change Zero: no nitrogen lost Loses nitrogen as \(\text{NH}_4^+\)

Connecting to the Urea Cycle

Amino Acids Transamination Glutamate GDH
\(\text{NH}_4^+\)
 CPS I Carbamoyl-P AST Aspartate UREA CYCLE (liver mitochondria)

How to Trace a Transamination

1
Identify substrates: Which amino acid is the \(\text{NH}_2\) donor? Which \(\alpha\)-keto acid is the acceptor?
2
Remove the amino group: Replace the donor's \(\alpha\text{-NH}_2\) with a \(\text{=O}\) (carbonyl). The donor becomes its corresponding keto acid.
3
Add the amino group: Replace the acceptor's \(\alpha\text{-C=O}\) with \(\text{-NH}_2\). The acceptor becomes the corresponding amino acid.
4
Check balance: No nitrogen is created or destroyed. You should have one new amino acid and one new keto acid.
5
Identify the enzyme: Name it by combining the amino acid donor name with "aminotransferase" (e.g., alanine aminotransferase).

Example 1: ALT Reaction

Alanine
\(\text{CH}_3\text{-CH}(\text{NH}_2)\text{-COOH}\)
 +
\(\alpha\)-Ketoglutarate
\(^{-}\text{OOC-CO-CH}_2\text{-CH}_2\text{-COO}^{-}\)
 ALT + PLP Pyruvate
\(\text{CH}_3\text{-CO-COOH}\)
 + Glutamate
\(^{-}\text{OOC-CH}(\text{NH}_2)\text{-CH}_2\text{-CH}_2\text{-COO}^{-}\)
\(\text{NH}_2\)

Example 2: AST Reaction

Aspartate
\(^{-}\text{OOC-CH}(\text{NH}_2)\text{-CH}_2\text{-COO}^{-}\)
 +
\(\alpha\)-Ketoglutarate
\(^{-}\text{OOC-CO-CH}_2\text{-CH}_2\text{-COO}^{-}\)
 AST + PLP Oxaloacetate
\(^{-}\text{OOC-CO-CH}_2\text{-COO}^{-}\)
 + Glutamate
\(^{-}\text{OOC-CH}(\text{NH}_2)\text{-CH}_2\text{-CH}_2\text{-COO}^{-}\)
\(\text{NH}_2\)

Example 3: Reverse Transamination

Because transaminases are freely reversible, cells can also synthesize non-essential amino acids. For example, if the body needs more alanine:

This is exactly the ALT reaction run in reverse. The direction depends on the relative concentrations of substrates and products, not on any intrinsic preference of the enzyme.

Common Mistakes

✕ Confusing PLP with \(\text{NAD}^+\)
PLP (vitamin \(\text{B}_6\)) is the coenzyme for transamination. \(\text{NAD}^+\) is used in oxidative deamination by glutamate dehydrogenase. They serve different reactions.
✕ Thinking nitrogen is lost
Transamination transfers nitrogen: no \(\text{NH}_4^+\) is released. Nitrogen is only "lost" as free ammonia during oxidative deamination.
✕ Ignoring reversibility
Students often treat transaminase reactions as one-directional. They are freely reversible: the same enzyme can synthesize or degrade amino acids depending on conditions.

Summary: Key Reactions

Feature ALT AST GDH
Type Transamination Transamination Oxidative deamination
Amino acid Alanine Aspartate Glutamate
Keto acid product Pyruvate Oxaloacetate \(\alpha\text{-KG}\)
Coenzyme PLP PLP \(\text{NAD}^+/\text{NADP}^+\)
N product Glutamate Glutamate \(\text{NH}_4^+\)
Clinical marker Liver damage Heart/liver damage -

Question 1 of 5

What is the coenzyme required by all aminotransferases?

Question 2 of 5

In the ALT reaction, alanine transfers its amino group to \(\alpha\)-ketoglutarate. What are the two products?

Question 3 of 5

During the ping-pong mechanism, the enzyme alternates between two forms. What are they?

Question 4 of 5

Which of the following best distinguishes transamination from oxidative deamination?

Question 5 of 5

A patient's blood test reveals markedly elevated ALT with a mildly elevated AST. This pattern is most consistent with damage to which organ?