Homocystine reductase

Since the coenzyme from vitamin is required in two distinct enzyme reactions, i.e., remethylation of homocystine and catabolism of methylmalonic acid, the fundamental defect must involve a step in converting to its coenzymes. Formation of both deoxyadenosyl B and methyl B requires a prior reductive step catalyzed by cobalamin reductase, which appears to be the defective enzyme in this variant (Hogervorst et al., 2002) (Fig. 20.4). 

Leclerc D, Wilson A Dumas R, Gafiiik C, Song D, Watkins D, Heng HH, Rommens JM, Scherer SW, Rosenblatt DS, Gravel RA (1998) Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystin-uria. Proc Natl Acad Sci U S A 95 3059-3064... 

The complete system contained per milliliter of solution 30 micromoles of dibasic ammonium phosphate, 0.2 micromole of DPN, 40 y of GSSG, 100 micromoles of alcohol, 200 y of alcohol dehydrogenase, 54 y of GSSG reductase, 0.7 micromole of homocystine, and 1.1 mg. of partially purified transhydrogenase.. fter 30 min. at 37° the mixture was analyzed for homocysteine. 

The reduction of other SS compounds by crude liver preparations was found to be considerably more sluggish than the reactions with GSSG and homocystine. Since neither GSSG reductase nor the GSH hydrogen transferase are responsible for these reactions and no evidence for the participation of GSH has as yet been obtained, further discussion of these reactions will be omitted. 

Homocystine Homocystinuria B12 def. and cobalamin C, D, E, G Methylene tetrahydrofolate reductase def. Cystathioninuria (bacterial)... 

More recently Racket 116) reported that purified GSSG reductase of yeast and liver react also with DPNH, but at a slower rate than with TPNH. The DPNH-GSSG reaction is dependent on phosphate or arsenate and is inhibited by neutral salts, while the TPNH-GSSG reductase can be coupled to homocystine reduction. It should be remembered that a disulfide-thiol type of exchange reaction, described by Eldjam et al. (6) can explain the homocystine GSH interaction. 

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