D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.
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.
Suzuki
Y
Y
Department of Pediatrics, Gifu University School of Medicine, Gifu, Japan. ysuz@cc.gifu-u.ac.jp
Jiang
L L
LL
Souri
M
M
Miyazawa
S
S
Fukuda
S
S
Zhang
Z
Z
Une
M
M
Shimozawa
N
N
Kondo
N
N
Orii
T
T
Hashimoto
T
T
D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D003241:Consanguinity; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D007564:Japan; D008099:Liver / Q000201:enzymology; D008830:Microbodies / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D018901:Peroxisomal Disorders / Q000201:enzymology / Q000235:genetics*; D064029:Peroxisomal Multifunctional Protein-2; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D013237:Stereoisomerism
D005227:Fatty Acids; D009097:Multienzyme Complexes; D010168:Palmitates; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase; C010210:lignoceric acid