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Amino Acid Catabolism of Nitrogen

Amino Acid Catabolism of Nitrogen - Molecular Biochemistry...

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Amino Acid Catabolism: N Copyright © 1999-2008 by Joyce J. Diwan. All rights reserved. Molecular Biochemistry II
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There are multiple transaminase enzymes which vary in substrate specificity . Some show preference for particular amino acids or classes of amino acids as amino group donors, and/or for particular α -keto acid acceptors . H R 1 C COO - + R 2 C COO - NH 3 + O Transaminase H R 1 C COO - + R 2 C COO - O NH 3 + Transaminases (aminotransferases) catalyze the reversible reaction at right.
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Example of a Transaminase reaction: Aspartate donates its amino group, becoming the α -keto acid oxaloacetate. α -Ketoglutarate accepts the amino group, becoming the amino acid glutamate. aspartate α -ketoglutarate oxaloacetate glutamate Aminotransferase (Transaminase) COO - CH 2 CH 2 C COO - O COO - CH 2 HC COO - NH 3 + COO - CH 2 CH 2 HC COO - NH 3 + COO - CH 2 C COO - O + +
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In another example, alanine becomes pyruvate as the amino group is transferred to α -ketoglutarate. alanine α -ketoglutarate pyruvate glutamate Aminotransferase (Transaminase) COO - CH 2 CH 2 C COO - O CH 3 HC COO - NH 3 + COO - CH 2 CH 2 HC COO - NH 3 + CH 3 C COO - O + +
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Transaminases equilibrate amino groups among available α -keto acids. This permits synthesis of non-essential amino acids, using amino groups from other amino acids & carbon skeletons synthesized in a cell. Thus a balance of different amino acids is maintained, as proteins of varied amino acid contents are synthesized. Although the amino N of one amino acid can be used to synthesize another amino acid, N must be obtained in the diet as amino acids (proteins).
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Essential amino acids must be consumed in the diet. Mammalian cells lack enzymes to synthesize their carbon skeletons ( α -keto acids). These include: Isoleucine, leucine, & valine Lysine Threonine Tryptophan Phenylalanine (Tyr can be made from Phe.) Methionine (Cys can be made from Met.) Histidine (Essential for infants.)
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The prosthetic group of Transaminase is pyridoxal phosphate ( PLP ), a derivative of vitamin B 6 . pyridoxal phosphate (PLP) N H C O P O - O O OH CH 3 C H O - + H 2
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In the resting state, the aldehyde group of pyridoxal phosphate is in a Schiff base linkage to the ε -amino group of an enzyme lysine side-chain. N H C O P O - O O O - CH 3 HC - + H 2 N (CH 2 ) 4 Enz H + R H C COO - NH 2 Enzyme (Lys)-PLP Schiff base Amino acid
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The active site lysine extracts H + , promoting tautomerization, followed by reprotonation & hydrolysis. N H C O P O - O O O - CH 3 HC - + H 2 N H C H + R COO - Enz - Lys - NH 2 Amino acid-PLP Shiff base (aldimine) The α -amino group of a substrate amino acid displaces the enzyme lysine, to form a Schiff base linkage to PLP.
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The amino group remains on what is now pyridoxamine phosphate ( PMP ). A different α -keto acid reacts with PMP and the process reverses , to complete the reaction. N H C O P O - O O OH CH 3 CH 2 NH 2 H 2 R C COO - O - + Enz - Lys - NH 2 Pyridoxamine phosphate (PMP) α -keto acid What was an amino acid leaves as an α -keto acid .
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Several other enzymes that catalyze metabolism or synthesis of amino acids also utilize PLP as prosthetic group, and have mechanisms involving a Schiff base linkage of the amino group to PLP.
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