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CLYBL is a polymorphic human enzyme with malate synthase and β-methylmalate synthase activity
Laura Strittmatter1, Yang Li, Nathan J Nakatsuka
1Department of Molecular Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
Human Molecular Genetics
|December 17, 2013
Summary
Human CLYBL enzyme, linked to vitamin B12 levels, is identified as a malate/β-methylmalate synthase. This enzyme
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- CLYBL is a conserved human mitochondrial enzyme with an unknown function.
- It is expressed in various mammalian organs, notably brown fat and kidney.
- A common CLYBL polymorphism is linked to reduced vitamin B12 levels.
Purpose of the Study:
- To elucidate the molecular function of the CLYBL enzyme.
- To investigate the relationship between CLYBL and the mitochondrial vitamin B12 pathway.
- To confirm the impact of a common CLYBL polymorphism on protein expression.
Main Methods:
- Comparative genomics to analyze CLYBL co-expression and co-evolution.
- Structural modeling and enzyme kinetics to determine enzymatic activity.
- Analysis of a premature stop polymorphism in CLYBL.
Main Results:
- CLYBL is strongly co-expressed and co-evolved with components of the mitochondrial B12 pathway.
- The premature stop polymorphism results in a loss of CLYBL protein expression.
- CLYBL functions as a malate/β-methylmalate synthase, catalyzing the conversion of glyoxylate and acyl-CoA to malate or β-methylmalate.
Conclusions:
- CLYBL is a human malate/β-methylmalate synthase, previously thought to be absent in humans.
- The enzyme's role in human physiology and its mechanistic link to vitamin B12 metabolism require further investigation.
- CLYBL's function is integrated with the mitochondrial vitamin B12 pathway.
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