Formation of glycine and aminoacetone from L-threonine by rat liver mitochondria.
Threonine is a precursor of glycine in the rat, but the metabolic pathway involved is unclear. To elucidate this pathway, the biosynthesis of glycine, and of aminoacetone, from L-threonine were studied in rat liver mitochondrial preparations of differing integrities. In the absence of added cofactors, intact mitochondria formed glycine and aminoacetone in approximately equal amounts from 20 mM L-threonine, but exogenous NAD+ decreased and CoA increased the ratio of glycine to aminoacetone formed. In intact and freeze-thawed mitochondria, the ratio of glycine to aminoacetone formed was markedly sensitive to the concentration of L-threonine, glycine being the major product at low L-threonine concentrations. Disruption of mitochondrial integrity by sonication (1 min) decreased the ratio of glycine to aminoacetone formed, and in 20000 X g supernatant fractions from sonicated (3 min) mitochondria, aminoacetone was the major product. The main non-nitogenous two-carbon compound detected when intact mitochondria catabolized L-threonine to glycine was acetate, which was probably derived from deacylation of acetyl-CoA. These results suggest that glycine formation from L-threonine in rat liver mitochondria occurred primarily by the coupled activities of threonine dehydrogenase and 2-amino-3-oxobutyrate CoA-ligase, the extent of coupling between the enzymes being dependent upon a close physical relationship and upon the flux through the dehydrogenase reaction. In vivo glycine synthesis would predominate, and aminoacetone would be a minor product.
D000096:Acetone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D003065:Coenzyme A / Q000494:pharmacology; D005615:Freezing; D005998:Glycine / Q000378:metabolism*; D008293:Malates / Q000494:pharmacology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013010:Sonication; D013912:Threonine / Q000378:metabolism*
D008293:Malates; D009243:NAD; D000096:Acetone; D013912:Threonine; C030298:malic acid; D003065:Coenzyme A; D005998:Glycine; C006495:aminoacetone