Browsing by Author "Font-Sala, Candide"

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    A new role for carnitine in yeasts
    (Stellenbosch : Stellenbosch University, 2006-04) Font-Sala, Candide; Bauer, Florian; Pretorius, I. S.; Stellenbosch University. Faculty of Science. Dept. of Microbiology.
    ENGLISH ABSTRACT: L-Carnitine (3-0H-4-N-trimethylaminobutanoic acid), also called vitamin Br, is required for the metabolism of fatty acids. Only one specific metabolic activity has been ascribed to L-carnitine in eukaryotic organisms, the transfer of activated acyl residues. In the case of yeast, this process involves the transfer of activated acetyl residues from the peroxisomes or the cytoplasm to the mitochondria. In Saccharomyces cerevisiae, 13-oxidation of fatty acids takes place exclusively in the peroxisomes. The process generates peroxisomal acetyl-CoA, and the activated acetyl-residue has to be transferred to the mitochondria for energy production. Acetyl-CoA and other acyl-CoAs however can not be transferred across intracellular membranes. The activated acetyl residue is therefore transferred to a molecule of carnitine to form acetyl carnitine, which can be shuttled across membranes. The reverse reaction, the transfer of the activated acetyl to free CoA-SH and the liberation of carnitine takes place in the mitochondria. This process is also referred to as the carnitine shuttle. Most organisms, including some yeast, fungi, plants and all mammals, but not S. cerevisiae, can synthesize carnitine from lysine and S-adenosyl-methionine. However, in humans, carnitine synthesis is insufficient to satisfy carnitine requirements, and dietary contributions are essential. Various diseases linked to carnitine deficiencies have been described. Such deficiencies include those found in neonates who, in the absence of carnitine, are unable to assimilate fatty acids from milk, or genetically inborn errors of metabolism, frequently linked to a defective transport of carnitine into cells. More recent literature suggests that carnitine supplementation can have beneficial effects in a number of pathologies, and can also provide some protection against diabetes and liver disease. It has furthermore been suggested that carnitine can contribute to slowing brain aging and to improve conditions of patients suffering from neurodegenerative diseases such as Alzheimer's disease. The accumulation of such data may suggest that carnitine plays additional, as yet unrecognized roles in cellular physiology. In the study reported here, the yeast S. cerevisiae was used to identify possible additional roles for carnitine in cellular metabolism. The study furthermore attempted to identify genes that may be associated with such additional roles. The data show that carnitine supplementation of the growth substrate can protect yeast cells from hyper osmotic and high temperature stress. These protective effects are independent of the metabolic role of carnitine, since deletion of genes that are essential for the carnitine shuttle does not reduce the protective effect. The investigation also suggests that there are no other metabolic roles for carnitine in yeast than the carnitine shuttle, and that it therefore may act as a compatible solute in osmo-protection. The data also indicate a role for PH087, previously identified as a low affinity inorganic phosphate carrier, in the protective effect of carnitine. PH087 overexpression strains accumulate higher concentrations of carnitine, whereas pho87t:. strains contain less carnitine than the corresponding wild type strain. The data therefore suggest either a direct or a regulatory role of the protein in carnitine uptake.