Carnitine metabolism in the vitamin B-12-deficient rat.
In vitamin B-12 (cobalamin) deficiency the metabolism of propionyl-CoA and methylmalonyl-CoA are inhibited secondarily to decreased L-methylmalonyl-CoA mutase activity. Production of acylcarnitines provides a mechanism for removing acyl groups and liberating CoA under conditions of impaired acyl-CoA utilization. Carnitine metabolism was studied in the vitamin B-12-deficient rat to define the relationship between alterations in acylcarnitine generation and the development of methylmalonic aciduria. Urinary excretion of methylmalonic acid was increased 200-fold in vitamin B-12-deficient rats as compared with controls. Urinary acylcarnitine excretion was increased in the vitamin B-12-deficient animals by 70%. This increase in urinary acylcarnitine excretion correlated with the degree of metabolic impairment as measured by the urinary methylmalonic acid elimination. Urinary propionylcarnitine excretion averaged 11 nmol/day in control rats and 120 nmol/day in the vitamin B-12-deficient group. The fraction of total carnitine present as short-chain acylcarnitines in the plasma and liver of vitamin B-12-deficient rats was increased as compared with controls. When the rats were fasted for 48 h, relative or absolute increases were seen in the urine, plasma, liver and skeletal-muscle acylcarnitine content of the vitamin B-12-deficient rats as compared with controls. Thus vitamin B-12 deficiency was associated with a redistribution of carnitine towards acylcarnitines. Propionylcarnitine was a significant constituent of the acylcarnitine pool in the vitamin B-12-deficient animals. The changes in carnitine metabolism were consistent with the changes in CoA metabolism known to occur with vitamin B-12 deficiency. The vitamin B-12-deficient rat provides a model system for studying carnitine metabolism in the methylmalonic acidurias.
Brass
E P
EP
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Stabler
S P
SP
D000108:Acetylcarnitine / Q000652:urine; D000818:Animals; D001835:Body Weight; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005215:Fasting; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D051381:Rats; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000378:metabolism* / Q000652:urine
C003223:propionylcarnitine; D000108:Acetylcarnitine; D008764:Methylmalonic Acid; D002331:Carnitine