Transamination, enzyme inactivation

Acyl-CoA dehydrogenase (especially butyryl-CoA dehydrogenase) is irreversibly inactivated by methylene cyclopropylacetyl-CoA through the formation of covalent adduct with the FAD of the enzyme. The inhibitor is derived by transamination... 

Gene inactivation studies in S. peucetius have identified the involvement of dnmj, dnmU and dnmV in the biosynthesis of dTDP-L-daunosamine [56,66]. Based on sequence similarities to known proteins, and in particular to the enzymes found in the dTDP-L-epivancosamine pathway, it is possible to deduce the functions and reaction order of these gene products [123]. After formation of the labile 3,4-diketone intermediate, DnmJ directs biosynthesis towards aminosugars by regio- and stereospecific transamination to produce a 2,3,6-trideoxy skeleton with a C-3 amino substituent [66] (Scheme 6, step 24). The biosynthesis is completed by DnmU-catalysed 3,5-epimerization... 

The reactive, transaminated product (5) can either engage in alkylation reaction with an active-site residue or can aromatize. Both processes would yield an inactivated enzyme. 

L-cSer K. values of the order of 10 —10 M (for the D-iso-mer affinities are 20-100 fold lower). L-cycloserine is not bound covalently by the lyase proteins (as opposed to the transaminases) from the adducts gel-filtration will release native (labile) apoenzymes and coenzyine-inhibitor imines, yielding mainly PMP and PM on acidification (Fig.4 ). If our cri-terium based on the occurrence of abortive half-transamination from cSer to PLP is valid, the fairly high sensitivity of lyases 6 and h. to inhibition by L-cSer (though atypical in comparison with transaminase inactivation) indicates the probable involvement of PMP-ketimines ( or tautomeric quinonold Schiff bases, see Fig.1)in enzymic Of B-elimination reactions. 

The oxidative pathway of tryptophan metabolism is shown in Figure 3. Kynureninase is a pyridoxal phosphate-dependent enzyme, and in deficiency its activity is lower than that of tryptophan dioxygenase, so that there is an accumulation of hydroxy-kynurenine and kynurenine, resulting in greater metabolic flux through kynurenine transaminase and increased formation of kynurenic and xanthurenic acids. Kynureninase is exquisitely sensitive to vitamin Bg deficiency because it undergoes a slow inactivation as a result of catalysing the half-reaction of transamination instead of its normal reaction. The resultant enzyme with pyridoxamine phosphate at the catalytic site is catalytically inactive and can only be reactivated if there is an adequate concentration of pyridoxal phosphate to displace the pyridoxamine phosphate. 

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