Catabolism of Proteins Deamination Complexity of protein catabolism

Catabolism of Proteins: Deamination § Complexity of protein catabolism is much more than that of fats or carbohydrates § § Each of the 20 -amino acids have a unique degradation pathway Protein degradation pathways comprise of: § § § Removal of ammonia by deamination Conversion of ammonia into urea Conversion of the remaining amino acid skeleton into a compound that enters the citric acid cycle © 2016 Cengage Learning. All Rights Reserved.

Transamination § § Exchange of –NH 2 group of the amino acid with the keto group of -keto-glutarate to form a new -keto acid and glutamate Occurs in two stages © 2016 Cengage Learning. All Rights Reserved.

Figure 29. 14 - Mechanism for the Enzyme-Catalysed, PLP-dependent Transamination of an -Amino Acid © 2016 Cengage Learning. All Rights Reserved.

Transimination § The PLP–enzyme reacts with an -amino acid to yield a PLP–amino acid imine and expelled enzyme as the leaving group © 2016 Cengage Learning. All Rights Reserved.

Tautomerization and Hydrolysis § The basic lysine residue in the expelled enzyme from transamination deprotonates the acidic position of the amino acid § § Reprotonation results in pyridoxamine phosphate– -keto acid (PMP– -keto acid) Hydrolysis of PMP– -keto acid imine results in proton transfer and expulsion of PMP as the leaving group © 2016 Cengage Learning. All Rights Reserved.

Tautomerization and Hydrolysis © 2016 Cengage Learning. All Rights Reserved.

Regeneration of PLP from PMP § § Signals the end of the catalytic cycle Another transamination reaction between PMP and an -keto acid produces PLP and a glutamate © 2016 Cengage Learning. All Rights Reserved.

Worked Example § Determine the -keto acid formed on transamination of leucine © 2016 Cengage Learning. All Rights Reserved.

Worked Example § Solution: § Leucine and -ketoglutarate are positioned so that the groups to be exchanged are aligned § Easier to predict the products of transamination reactions © 2016 Cengage Learning. All Rights Reserved.