Inborn errors of cobalamin metabolism: effect of cobalamin supplementation in culture on methylmalonyl CoA mutase activity in normal and mutant human fibroblasts

Biochemical Genetics
H F Willard, L E Rosenberg

Abstract

We have examined the effect of addition of hydroxocobalamin to growth medium on the activity of the adenosylcobalamin-requiring enzyme methylmalonyl CoA mutase in normal human fibroblasts and in mutant human fibroblasts derived from patients with inherited methylmalonicacidemia. The mutant cell lines were assigned to four distinct genetic complementation groups (cbl A, cbl B, cbl C, and cbl D), each deficient in some step in the synthesis of adenosylcobalamin from hydroxocobalamin. After control cells were grown in cobalamin-supplemented medium, mutase holoenzyme activitiy increased markedly in a time- and concentration-dependent fashion. Growth in cobalamin-supplemented medium had no effect on mutase activity in some mutant lines belonging to the cbl B group, while activity increased severalfold in other cbl B mutants and in all cbl A, cbl C, and cbl D mutants examined, although mutase activity was still less than 10% of control. Comparison of mutase holoenzyme activity and total propionate pathway activity suggests that enhancement of mutase activity in mutant cells after cobalamin supplementation to values 5--10% of control may be sufficient to overcome the inherited metabolic block and to restore total pathway activity to n...Continue Reading

References

Oct 10, 1977·Biochemical and Biophysical Research Communications·H F Willard, L E Rosenberg
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Citations

Jan 1, 1989·Journal of Inherited Metabolic Disease·R A Chalmers
Jan 1, 1985·Journal of Inherited Metabolic Disease·H KakinumaY Nomoto
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·C L DrennanM L Ludwig
Aug 1, 1980·American Journal of Ophthalmology·D G CoganS H Mudd
Jan 7, 2014·Annual Review of Genomics and Human Genetics·L E Rosenberg
Dec 1, 1990·Genomics·S U NhamF D Ledley
Jan 1, 1985·Annals of the New York Academy of Sciences·K S Roth
Apr 20, 2018·Advances in Skin & Wound Care·Julian-Dario RembeEwa Klara Stuermer
Mar 1, 1988·Prenatal Diagnosis·B FowlerJ K Clayton
Jun 1, 1990·American Journal of Hematology·B A CooperD Watkins

Related Concepts

Amino Acid Metabolism, Inherited Disorders
Isomerase
Malonates
Methylmalonic Acid
Methylmalonyl-CoA Mutase
Variation (Genetics)
Eritron

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