Transamination

(1)

ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 3: PROTEINS

T T r r a a n n s s a a m m i i n n a a t t i i o o n n

B B B Y Y Y

D D R R . . P P O O U U L L A A M M I I A A D D H H I I K K A A R R Y Y M M U U K K H H E E R R J J E E E E A A S S S S I I S S T T A A N N T T P P R R O O F F E E S S S S O O R R

D D E E P P A A R R T T M M E E N N T T O O F F Z Z O O O O L L O O G G Y Y

N N A A R R A A J J O O L L E E R R A A J J C C O O L L L L E E G G E E

(2)

ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 3: PROTEINS

Transamination, a chemical reaction that transfers

an amino group to a ketoacid to form new amino

acids. This pathway is responsible for the

deamination of most amino acids. This is one of the

major degradation pathways, which convert essential

amino acids to non-essential amino acids (amino

acids that can be synthesized de novo by the

organism).

(3)

Transamination in biochemistry is accomplished by enzymes called transaminases or aminotransferases. α- ketoglutarate acts as the predominant amino-group acceptor and produces glutamate as the new amino acid.

Amino acid + α-ketoglutarate ↔ α-keto acid

+ Glutamate

(4)

Glutamate's amino group, in turn, is transferred to oxaloacetate in a second transamination reaction yielding aspartate.

Glutamate + oxaloacetate ↔ α-ketoglutarate

+ aspartate

(5)

Aminotransfer reaction between an amino acid and an alpha-keto acid

(6)

Mechanism of Action:

Transamination catalyzed by aminotransferase occurs in two stages.

In the first step, the α amino group of an amino acid

is transferred to the enzyme, producing the

corresponding α-keto acid and the aminated enzyme.

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ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 3: PROTEINS

During the second stage, the amino group is transferred to the keto acid acceptor, forming the amino acid product while regenerating the enzyme.

The chirality of an amino acid is determined during

transamination.

(8)

For the reaction to complete, aminotransferases require participation of aldehyde containing coenzyme, pyridoxal-5'-phosphate (PLP), a derivative of Pyridoxine (Vitamin B6).

The amino group is accommodated by conversion of this coenzyme to pyridoxamine-5'-phosphate (PMP).

(9)

PLP is covalently attached to the enzyme via a Schiff Base linkage formed by the condensation of its aldehyde group with the ε-amino group of an enzymatic Lys residue.

The Schiff base, which is conjugated to the enzymes

pyridinium ring is the focus of the coenzyme activity.

(10)

ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 3: PROTEINS

(11)

The product of transamination reactions depend on the

availability of α-keto acids. The products usually are

either alanine, aspartate or glutamate, since their

corresponding alpha-keto acids are produced through

metabolism of fuels. Being a major degradative aminoacid

pathway, lysine, proline and threonine are the only three

amino acids that do not always undergo transamination

and rather use respective dehydrogenase.

(12)

Alternative Mechanism:

A second type of transamination reaction can be described as a nucleophilic substitution of one amine or amide anion on an amine or ammonium salt. For example, the attack of a primary amine by a primary amide anion can be used to prepare secondary amines:

RNH

2

+ R'NH− → RR'NH + NH

²⁻

(13)

Symmetric secondary amines can be prepared using Raney nickel (2RNH

2

→ R

2

NH + NH

3

). And finally, quaternary ammonium salts can be dealkylated using ethanolamine:

R

4

N

⁺

+ NH

2

CH

2

CH

2

OH → R

3

N + RN+H

2

CH

2

CH

2

OH

Aminonaphthalenes also undergo transaminations.

(14)

ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 3: PROTEINS

T T y y p p e e s s o o f f a a m m i i n n o o t t r r a a n n s s f f e e r r a a s s e e : :

Transamination is mediated by several different

aminotransferase enzymes. These may be specific for

individual amino acids, or they may be able to process a

group of chemically similar ones. The latter applies to the

group of the branched-chain amino acids, which

comprises leucine, isoleucine, and valine. The two

common types of aminotransferases are Alanine

(15)

aminotransferase (ALT) and Aspartate aminotransferase

(AST).

(16)

T T H H A A N N K K Y Y O O U U