Biomedical subjects

C S Long

Publications and source records attributed to C S Long.

39 records · Page 3Linked to original sources

PubMed1983

Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat.

The requirement for carnitine and the malonyl-CoA sensitivity of carnitine palmitoyl-transferase I (EC 2.3.1.21) were measured in isolated mitochondria from eight tissues of animal or human origin using fixed concentrations of palmitoyl-CoA (50 microM) and albumin (147 microM). The Km for carnitine spanned a 20-fold range, rising from about 35 microM in adult rat and human foetal liver to 700 microM in dog heart. Intermediate values of increasing magnitude were found for rat heart, guinea pig liver and skeletal muscle of rat, dog and man. Conversely, the concentration of malonyl-CoA required for 50% suppression of enzyme activity fell from the region of 2-3 microM in human and rat liver to only 20 nM in tissues displaying the highest Km for carnitine. Thus, the requirement for carnitine and sensitivity to malonyl-CoA appeared to be inversely related. The Km of carnitine palmitoyltransferase I for palmitoyl-CoA was similar in tissues showing large differences in requirement for carnitine. Other experiments established that, in addition to liver, heart and skeletal muscle of fed rats contain significant quantities of malonyl-CoA and that in all three tissues the level falls with starvation. Although its intracellular location in heart and skeletal muscle is not known, the possibility is raised that malonyl-CoA (or a related compound) could, under certain circumstances, interact with carnitine palmitoyltransferase I in non-hepatic tissues and thereby exert control over long chain fatty acid oxidation.

Acyl Coenzyme A↗

PubMed1982

Kinetics of carnitine-dependent fatty acid oxidation: implications for human carnitine deficiency.

The relationship between the concentration of carnitine and the oxidation of oleate was examined in homogenates prepared from skeletal muscle, liver, kidney, and heart of the rat, and from canine and human skeletal muscle. the carnitine content of these tissues in situ spanned a wide range, from about 0.1 mumol per gram in rat liver to about 3.0 mumol per gram in human muscle. The concentration of carnitine required for half-maximal rates of fatty acid oxidation in vitro also varied greatly (10 to 15 microM for rat liver to 200 to 400 microM for human muscle), and in rough proportion to the normal carnitine content of the tissues. For any given tissue, the carnitine content seems to be set at a level necessary for optimal rates of fatty acid oxidation. The data provide a plausible explanation for the fact that muscle fatty acid metabolism is severely impaired in the syndrome of human carnitine deficiency, since measured carnitine levels are in the range expected to limit substantially the capacity for fatty acid oxidation.

Animals↗

PubMedDate not supplied

Adrenergic hormones and control of cardiac myocyte growth.

The molecular mechanisms of cardiac myocyte growth are relevant to important problems in cardiovascular disease. A cell culture model has been developed to explore the role of adrenergic hormones in cardiac myocyte growth and gene expression. Activation of a cardiac myocyte alpha 1-adrenergic receptor by catecholamines induces hypertrophic growth of neonatal rat cardiac myocytes and initiates selective increases in contractile protein gene transcription. These effects on growth and gene expression do not depend on contractile activity. The cardiac myocytes contain at least two subtypes of alpha 1-adrenergic receptors and at least three isoforms of protein kinase C (PKC). A distinct alpha 1 receptor subtype may mediate hypertrophy and gene transcription. Different isoforms of PKC are translocated to different intracellular sites on activation, and there is evidence that the beta-PKC isoform may be an element in the signal transduction pathway from an alpha 1 receptor at the surface to the cardiac myocyte nucleus. Growth regulation through a beta-adrenergic receptor can also be demonstrated in the culture model. The growth response mediated through a beta-adrenergic receptor differs in several respects from that transduced through an alpha 1-adrenergic receptor.

Catecholamines↗