Gluconeogenesis from propionate in kidney and liver of the vitamin B12-deficient rat.
1. Kidney-cortex slices and the perfused livers of vitamin B(12)-deficient rats removed propionate from the incubation and perfusion media at 33 and 17% respectively of the rates found with tissues from rats receiving either a normal or a vitamin B(12)-supplemented diet. There was a corresponding fall in the rates of glucose synthesis from propionate in both tissues. 2. The addition of hydroxocobalamin or dimethylbenzimidazolylcobamide coenzyme to kidney-cortex slices from vitamin B(12)-deficient rats in vitro failed to restore the normal capacity for propionate metabolism. 3. Although the vitamin B(12)-deficient rat excretes measurable amounts of methylmalonate, no methylmalonate production could be detected (probably because of the low sensitivity of the method) when kidney-cortex slices or livers from deficient rats were incubated or perfused with propionate. 4. The addition of methylmalonate (5mm) to kidney-cortex slices from rats fed on a normal diet inhibited gluconeogenesis from propionate by 25%. 5. Methylmalonate formation is normally only a small fraction of the flux through methylmalonyl-CoA. This fraction increases in vitamin B(12)-deficient tissues (as shown by the urinary excretion of methylmalonate) presumably because the concentration of methylmalonyl-CoA rises as a result of low activity of methylmalonyl-CoA mutase (EC 5.4.99.2). Slow removal of methylmalonyl-CoA might depress propionate uptake owing to the reversibility of the steps leading to methylmalonyl-CoA formation.
D000818:Animals; D003065:Coenzyme A / Q000378:metabolism; D003067:Coenzymes / Q000494:pharmacology; D003864:Depression, Chemical; D005943:Gluconeogenesis; D006879:Hydroxocobalamin / Q000494:pharmacology; D007535:Isomerases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008314:Malonates / Q000096:biosynthesis / Q000494:pharmacology / Q000652:urine; D010477:Perfusion; D011422:Propionates / Q000378:metabolism*; D051381:Rats; D014805:Vitamin B 12 / Q000494:pharmacology; D014806:Vitamin B 12 Deficiency / Q000378:metabolism*
D003067:Coenzymes; D008314:Malonates; D011422:Propionates; D007535:Isomerases; D014805:Vitamin B 12; D006879:Hydroxocobalamin; D003065:Coenzyme A