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R Druyan

Publications and source records attributed to R Druyan.

8 recordsLinked to original sources

Studies of cytochrome synthesis in rat liver.

The incorporation of radioactive amino acids and of delta-amino[2,3-(3)H(2)]laevulinate into rat liver cytochromes b(5) and c and cytochrome oxidase has been examined with and without protein-synthesis inhibitors. Cycloheximide promptly inhibits labelling of both haem and protein for cytochrome c in parallel fashion. Although incorporation of (14)C-labelled amino acid into microsomal cytochrome b(5) is also rapidly inhibited, cycloheximide incompletely inhibits haem labelling of cytochrome b(5) and cytochrome a+a(3), and inhibition occurs only after repeated antibiotic injections. The possibility of apo-protein pools, or of haem exchange, with a rapidly renewed ;free' haem pool, is considered. Consistent with this model is the observation of non-enzymic haem exchange in vitro between cytochrome b(5) and methaemoglobin. Chloramphenicol, injected intravenously over 5h, results in a 20-40% decrease in incorporation of delta-amino[2,3-(3)H(2)]laevulinate into haem a+a(3) and haem of cytochromes b(5) and c. With the dosage schedule of chloramphenicol studied, amino acid labelling of total liver protein and of cytochrome c was not inhibited. Similarly, ferrochelatase activity was not decreased.

Journal Article↗

The effect of exogenous -aminolaevulinate on rat liver haem and cytochromes.

The activity of delta-aminolaevulinate synthetase is generally regarded as rate-limiting for hepatic haem biosynthesis. It has been suggested that cytochrome synthesis may also be regulated by changes in delta-aminolaevulinate synthetase activity. This hypothesis was studied by injecting product, delta-aminolaevulinate, into adult rats over a 4-240h period. The concentrations of hepatic mitochondrial cytochromes a, b, c and c(1) were unchanged by treatment with delta-aminolaevulinate, allylisopropylacetamide or phenobarbital. In control animals, total microsomal haem content equalled the sum of cytochromes b(5) plus P-450. After delta-aminolaevulinate administration the total amount of microsomal haem, measured as the pyridine haemochromogen, exceeded these components, indicating the formation of a ;free' haem pool. Haem synthesis does not appear rate-limiting for hepatic cytochrome synthesis in the adult rat.

5-Aminolevulinate Synthetase↗

Haem a, cytochrome c and total protein turnover in mitochondria from rat heart and liver.

Haem a and cytochrome c were isotopically labelled in mitochondria from rat heart and liver after injection of delta-amino[2,3-(3)H(2)]laevulate, a specific haem precursor. [guanido-(14)C]Arginine or l-[4,5-(3)H(2)]leucine were used to label mitochondrial proteins. Half-lives were measured from biological decay in vivo and were similar (5.5-6.2 days) for haem a, cytochrome c and [(14)C]arginine-labelled proteins. Labelling of hepatic mitochondrial proteins with [(3)H(2)]leucine resulted in a prolonged apparent half-life.

Amino Acids↗

Intramitochondrial localization of delta-aminolaevulate synthetase and ferrochelatase in rat liver.

Intramitochondrial loci for delta-aminolaevulate synthetase and ferrochelatase, the initial and final enzymes in haem synthesis, have been found in rat liver. Two different methods of fractionation were applied to mitochondria: (a) sonication and density-gradient centrifugation; (b) treatment with digitonin and differential centrifugation. Similar results were obtained with each technique. delta-Aminolaevulate synthetase is distributed similarly to two known matrix enzymes, malate dehydrogenase and glutamate dehydrogenase. Ferrochelatase is firmly bound to the the inner mitochondrial membrane. These results are considered in terms of the regulation of haem synthesis and in relation to mitochondrial biogenesis.

Amino Acids↗