QSAR of a Series of Carnitine Acetyl Transferase (CAT) Substrates

Abstract

Carnitine acyl transferases are a family of enzymes that differ with respect to subcellular localization and substrate specificity. Carnitine acetyl transferase (CAT) is mainly found in the mitochondrial matrix where it is postulated to play a key role in stabilizing the CoA-SH/CoA-SAc ratio.¹ CAT catalyses the reversible reaction:

$$Acetyl - L - carnitine + Coa - SH \leftrightarrow L - carnitine + acetyl - Coa$$

that has an equilibrium constant equal to 0.6. The kinetic enzymatic mechanism for CAT follows a random-order equilibrium reaction where Michaelis constant (K _m ) approximates true dissociation constant (K _s ) and binding of one substrate has little or no effect on binding of the second.² The aim of this work is to study a set of acyl-CoA derivatives that includes linear, branched and cycloalkyl, and unsaturated substituents ^2,3,4 A QSAR approach is used to investigate the influence of such substituents on kinetic parameters, K _m and V’max.