Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency
Summary
A patient with Zellweger syndrome-like symptoms had deficient peroxisomal 3-oxoacyl-CoA thiolase, leading to impaired fatty acid oxidation and bile acid synthesis. Restoring this enzyme corrected the metabolic defects.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Peroxisomal beta-oxidation is crucial for metabolizing very-long-chain fatty acids (VLCFAs) and bile acid precursors.
- Defects in peroxisomal pathways are associated with severe genetic disorders like Zellweger syndrome.
Observation:
- A patient presented with clinical features resembling Zellweger syndrome, including elevated VLCFAs and bile acid intermediates.
- Liver peroxisomal beta-oxidation was significantly reduced (less than 10% of controls).
Findings:
- Immunoblotting revealed a deficiency in peroxisomal 3-oxoacyl-CoA thiolase, an enzyme essential for beta-oxidation.
- Adding purified 3-oxoacyl-CoA thiolase restored the enzyme's activity in the patient's liver homogenate.
Implications:
- The deficiency of peroxisomal 3-oxoacyl-CoA thiolase is identified as the cause of impaired VLCFA and bile acid metabolism in this patient.
- This suggests a single peroxisomal 3-oxoacyl-CoA thiolase isoform is involved in shortening both VLCFAs and coprostanols.
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