4-Thia-trans-2-alkenoyl-CoA derivatives: properties and enzymatic reactions.
4-Thiaacyl-CoA analogues, in which the 4-methylene group is replaced by a thioether sulfur atom, represent new chromophoric substrates of acyl-CoA dehydrogenases and oxidase. The corresponding 4-thia-trans-2-enoyl-CoA products exhibit a strong new absorption band (extinction coefficient 22 mM-1 cm-1) that is red shifted from 312 to 338 nm upon binding to the medium-chain acyl-CoA dehydrogenase. 4-Thiaoctanoyl-CoA reduces the dehydrogenase several-fold slower than octanoyl-CoA, although in turnover it is dehydrogenated 1.5-fold faster. The redox potential of 4-thia analogues is some 30 mV more negative than that of their unsubstituted counterparts. 4-Thia-trans-2-enoyl-CoA derivatives are slowly hydrated by enoyl-CoA hydratase (EC 4.2.1.17) to the corresponding thiohemiacetal which fragments nonenzymatically to 1 equiv each of malonylsemialdehyde-CoA and alkanethiol. This fragmentation reaction might explain the release of methanethiol during the transamination pathway of methionine degradation. 4-Oxaoctanoyl-CoA is a much poorer substrate and kinetic reductant of acyl-CoA dehydrogenase and oxidase than the 4-thia analogue. The corresponding enoyl-CoA product is also fragmented by the hydratase, yielding butanol and malonylsemialdehyde-CoA. Thus, 4-heterosubstituted acyl-CoA derivatives provide new tools for the study of beta-oxidation enzymes.
Lau
S M
SM
Department of Chemistry and Biochemistry, University of Delaware, Newark 19716.
Brantley
R K
RK
Thorpe
C
C
D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D003065:Coenzyme A / Q000032:analysis* / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D010084:Oxidation-Reduction; D013552:Swine
D008715:Methionine; D000445:Aldehyde Oxidoreductases; C021351:hexadecanal dehydrogenase (acylating); D004746:Enoyl-CoA Hydratase; D003065:Coenzyme A