L18 - Transamination and Deamination Reactions

The four AAs important in the transport and distribution of N group & in the Urea cycle

A, E, Q, D; They can also be easily converted to TCA intermediates

Pyruvate is the α-ketoacid of what AA

A

Oxaloacetate is the α-ketoacid of what AA

D

α-Ketoglutarate is the α-ketoacid of what AA

E

Transamination

Removal of nitrogen from AAs; required for AA catabolism; catalyzed by aminotransferases or transaminases

α-amino group of AA is transferred to α-keto acid (Usually α-KG)

Pyridoxal Phosphate (PLP)

Essential coenzyme for transamination; derived from Vitamin B6

Is converted to pyridoxamine phosphate (PMP) during the process

Can interact with enzyme to form internal aldimine

Can interact with donating AA to form external aldimine

α-KG then comes in to grab the amino group

Why is the amino group never released into the cytosol during transamination

Releasing amino group causes formation of toxic ammonia

Transamination pathway

_L-alanine + E(PLP) → E(PMP) + pyruvate

E(PMP) + 2-oxoglutarate → E(PLP) + _L-glutamate

Reversible

Two important Aminotransferase enzymes

Alanine Aminotransferase (ALT) : _L-A + α-KG ←→ pyruvate + E

Aspartate Aminotransferase (AST): D + α-KG ←→ OAA + E

Reversible

How can ALT and AST indicate liver damage

High serum levels of ALT and AST indicates cirrhosis or some type of liver damage, causing these liver specific enzymes to leak

What AAs cannot enter transamination; why?

Any AAs with a secondary amino group; primary amines are required for transamination

Hydroxyproline, P for example

K and T cannot undergo transamination because the end products would form toxic metabolites

Is there any net deamination in transaminase reactions?

No because α-KG ends up becoming aminated to glutamate

How are glutamate levels controlled in the liver? Why does this need to happen?

Amino groups are collected from AA in the form of _L-Glutamate; having an excess can cause complications

Glutamate dehydrogenase (GDH) uses NAD⁺ in oxidative deamination to form α-KG + NADH + NH₄⁺

E → α-KG + NADH + NH₄⁺ via GDH

Ammonia then directly enters Urea cycle via CPS-I (Or another cycle) to avoid toxic buildup

Reversible

Glutamate dehydrogenase (GDH) Pathway

Major route for oxidative deamination; regenerates α-KG and provides ammonia for reutilization or urea cycle; occurs in mitochondria

E + NAD(P)⁺ → Intermediate + NAD(P)H

Intermediate + H₂O → α-KG + NH₄⁺

Reversible

How transamination and deamination is connected within different tissue types; what is this system referred to as?

Glucose-alanine cycle in muscle

Glutamine synthetase converts ammonia in tissues to prevent toxic buildup; then transported to liver to be converted to glutamate for usage

This is called transdeamination

Regulation of GDH

Allosterically regulated

High energy status (ATP, GTP, NADH) causes inhibition to allow protein synthesis

Low energy status (ADP, GDP) or in the presence of free AAs causes activation and allows deamination to occur

Glutaminase

Another deamination route

Q + H₂O → E + NH₃

Asparaginase

Another deamination route

_L-Asparagine (N) + H₂O → _L-Aspartate (D) + NH₃