D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.

Abstract

Peroxisomal beta-oxidation proceeds from enoyl-CoA through D-3-hydroxyacyl-CoA to 3-ketoacyl-CoA by the D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxy-acyl-CoA dehydrogenase bifunctional protein (d-bifunctional protein), and the oxidation of bile-acid precursors also has been suggested as being catalyzed by the d-bifunctional protein. Because of the important roles of this protein, we reinvestigated two Japanese patients previously diagnosed as having enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (L-bifunctional protein) deficiency, in complementation studies. We found that both the protein and the enzyme activity of the d-bifunctional protein were hardly detectable in these patients but that the active L-bifunctional protein was present. The mRNA level in patient 1 was very low, and, for patient 2, mRNA was of a smaller size. Sequencing analysis of the cDNA revealed a 52-bp deletion in patient 1 and a 237-bp deletion in patient 2. This seems to be the first report of D-bifunctional protein deficiency. Patients previously diagnosed as cases of L-bifunctional protein deficiency probably should be reexamined for a possible d-bifunctional protein deficiency.

• Authors: Y Suzuki, L L Jiang, M Souri, S Miyazawa, S Fukuda, Z Zhang, M Une, N Shimozawa, N Kondo, T Orii, T Hashimoto
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 61 Issue 5 Pg. 1153-62 (Nov 1997) ISSN: 0002-9297 [Print] United States
• PMID: 9345094 (Publication Type: Case Reports, Journal Article)

Chemical References

• Fatty Acids
• Multienzyme Complexes
• Palmitates
• RNA, Messenger
• 17-Hydroxysteroid Dehydrogenases
• 3-Hydroxyacyl CoA Dehydrogenases
• Hydro-Lyases
• Peroxisomal Multifunctional Protein-2
• HSD17B4 protein, human
• Enoyl-CoA Hydratase
• lignoceric acid

Topics

• 17-Hydroxysteroid Dehydrogenases
• 3-Hydroxyacyl CoA Dehydrogenases (genetics, metabolism)
• Consanguinity
• Enoyl-CoA Hydratase (metabolism)
• Fatty Acids (metabolism)
• Female
• Fibroblasts
• Fluorescent Antibody Technique
• Humans
• Hydro-Lyases (deficiency, genetics, metabolism)
• Infant
• Japan
• Liver (enzymology)
• Microbodies (enzymology)
• Multienzyme Complexes (deficiency, genetics)
• Oxidation-Reduction
• Palmitates (metabolism)
• Peroxisomal Disorders (enzymology, genetics)
• Peroxisomal Multifunctional Protein-2
• Polymerase Chain Reaction
• RNA, Messenger (genetics, metabolism)
• Sequence Deletion (genetics)
• Stereoisomerism