Substrate shuttles coenzymes

Coenzymes serve as recyclable shuttles—or group transfer reagents—that transport many substrates from their point of generation to their point of utilization. Association with the coenzyme also stabilizes substrates such as hydrogen atoms or hydride ions that are unstable in the aqueous environment of the cell. Other chemical moieties transported by coenzymes include methyl groups (folates), acyl groups (coenzyme A), and oligosaccharides (dolichol). 

Aminotransferases (transaminases) catalyze the reversible interconversions of pairs of a-amino and a-keto acids or of terminal primary amines and the corresponding aldehydes by a shuttle mechanism in which the enzyme alternates between its PLP form and the corresponding PMP form. In the first half-reaction the PLP form of the enzyme binds the amino acid (or amine) and forms the coenzyme-substrate Schiff s base. Cleavage of the C-a—H bond is then followed by protonation at C-4. Hydrolysis of the resulting ketimine then gives a keto acid (or aldehyde), leaving the enzyme in the PMP form. The latter is recycled to the PLP form by condensation with an a-keto acid, deprotonation at C-4, protonation at C-a and transaldimina-tion to release the a-amino acid formed. 

Oleate is an abundant 18-carbon monounsaturated fatty acid with a cis double bond between C-9 and C-10 (denoted A ). In the first step of oxidation, oleate is converted to oleoyl-CoA and, like the saturated fatty acids, enters the mitochondrial matrix via the carnitine shuttle (Fig. 17-6). Oleoyl-CoA then undergoes three passes through the fatty acid oxidation cycle to yield three molecules of acetyl-CoA and the coenzyme A ester of a A, 12-carbon unsaturated fatty acid, cis-A -dodecenoyl-CoA (Fig. 17-9). This product cannot serve as a substrate for enoyl-CoA hydratase, which acts only on trans double bonds. The auxiliary enzyme A, A -enoyl-CoA isomerase isomerizes the ci5-A -enoyl-CoA to the fra/J5-A -enoyl-CoA, which is converted by enoyl-CoA hydratase into the corresponding L-/3-hydroxyacyl-CoA (fra/75-A -dodecenoyl-CoA). This intermediate is now acted upon by the remaining enzymes of /3 oxidation to yield acetyl-CoA and the coenzyme A ester of a 10-carbon saturated fatty acid, decanoyl-CoA. The latter undergoes four more passes through the pathway to yield five more molecules of acetyl-CoA. Altogether, nine acetyl-CoAs are produced from one molecule of the 18-carbon oleate. 

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