Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.9.3.1 (
cytochrome oxidase
)
8,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A summary is presented of previous studies by other investigators of human
achondroplasia
and dyschondroplastic animal models. In addition, studies previously reported from our laboratories are discussed, and they demonstrate that defective oxidative energy metabolism is present in mitochondrial preparations from achondroplastic human subjects and rabbits (ac/ac) with chondrodystrophy. The results of the studies support the hypothesis discussed fully in the manuscript that a partial defect in mitochondrial oxidative metabolism in achondroplastic subjects is expressed specifically in the growth plates of the long bones because this tissue has the lowest oxygen tension of any bodily organ undergoing active proliferation, thus leading to the achondroplastic phenotype in humans and the ac/ac rabbit. In the ac/ac rabbit phosphorylation at the cytochrome c oxidase region (site III) of the terminal respiratory system was shown to be absent in mitochondrial preparations from the livers of newborn ac/ac rabbits. Normal-appearing littermates did not exhibit the defect. Studies of mitochondrial preparations from human skin fibroblasts (grown in tissue culture) from normal human subjects and subjects with homozygous
achondroplasia
demonstrated that concentrations of
cytochrome a3
were decreased approximately 80% in preparations from homozygous achondroplastic cells. Levels of
cytochrome a3
in heterozygous achondroplastic cells were intermediate between the levels in normal cells and homozygous achondroplastic cells demonstrating the effects of gene dosage. Determination of total heme a (as the pyridine hemochromogen) in the normal and achondroplastic preparations from human subjects showed that the observed decrease in concentration of
cytochrome a3
in the achondroplastic preparations was due to an absence of
cytochrome a3
and not to a change in its absorbancy (extinction coefficient).
...
PMID:Human achondroplasia: defective mitochondrial oxidative energy metabolism may produce the pathophysiology. 256 Feb 62
Mitochondria prepared from tissue culture cells (skin fibroblasts) from normal subjects and subjects with homozygous
achondroplasia
were studied to determine the concentrations of cytochromes a and a3 in the preparations. Cytochrome a3 was markedly decreased (80%) in the achondroplastic preparations with cytochrome a present in normal amounts. Determination of total heme a (as the pyridine hemochromogen) in the normal and achondroplastic preparations demonstrated that the observed decrease in concentration of
cytochrome a3
in the achondroplastic preparations was due to an absence of
cytochrome a3
and not to a change in its absorbancy (extinction coefficient). The decreased concentrations of
cytochrome a3
in the achondroplastic cells may decrease the reactivity or affinity of the mitochondrial oxidative systems for oxygen and result in the phenotypic expression of the disease.
...
PMID:Cytochrome a3 deficiency in human achondroplasia. 303 Apr 20
