Acylation, hydroxy

Benzisothiazole, 3-hydroxy-acylation, 6, 159 alkylation, 6, 159 chlorination, 6, 160 organophosphorus compounds, 6, 159... 

Hintz SR, Matern D, Strauss A, et al (2002) Early neonatal diagnosis of long-chain 3-hydroxy-acyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficiencies. Mol Genet Metab 75 120-127... 

The enoyl-CoAis then a substrate for the addition of water across the carbon-carbon double bond. This results in a (3-hydroxy-acyl-CoA compound, because the OH of water is added to the carbon further away from the carboxyl group ... 

Conjugate addition of water. The a,/3-unsaturated acyl CoA produced in step 1 reacts with water by a conjugate addition pathway (Section 19.14) to jneld a /3-hydroxy acyl CoA in a process catalyzed by the enzyme enoyl CoA hydratase. Water as nucleophile adds to the /3 carbon of the double bond, yielding an enolate ion intermediate, which is then protonated to yield an alcohol. 

Alcohol oxidation. The /3-hydroxy acyl CoA from step 2 is oxidized to a (-keto acyl CoA in a reaction catalyzed by the enzyme L-3-hydroxyacyl CoA dehydrogenase. As in the oxidation of glycerol 1-phosphatc to glyceralde-hyde 3-phosphate mentioned earlier, this alcohol oxidation requires as a coenzyme and yields reduced NADH/H" as by-product. 

Trifunctional Protein and Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiencies... 

Figure 55-14 Plasma profiles of plasma acylcarnitine butyl-ester derivatives. A, Normal control. B, Propionic acidemia. C, Short-chain acyl-CoA dehydrogenase deficiency. D, Isovaleric acidemia. E, Medium-chain acyl-CoA dehydrogenase deficiency. F, Very long-chain acyl-CoA dehydrogenase deficiency. G, Long-chain L-3-hydroxy acyl-CoA dehydrogenase deficiency.The symbol marks internal standards [ Hjj-acetylcarnitine (m/z 263) [ HaJ-propionylcarnitine (m/z 277) fH ]-butyrylcarnitlne (m/z 295) pHal-octanoylcarnitine (m/z 347) [ Haj-dodecanoylcarnltine (m/z 403) [ Haj-palmitoy I carnitine (m/z 459).

Fig. 23.18. Synthesis of the ketone bodies acetoacetate, P-hydroxybulyrate, and acetone. The portion of HMG-Co A shown in blue is released as acetyl CoA, and the remainder of the molecule forms acetoacetate. Acetoacetate is reduced to P-hydroxybutyrate or decarboxy-lated to acetone. Note that the dehydrogenase that interconverts acetoacetate and P-hydroxybutyrate is specific for the D-isomer. Thus, it differs from the dehydrogenases of P-oxidation, which act on 3-hydroxy acyl CoA derivatives and is specific for the L-isomer.

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