Table of Contents
Journal of Amino Acids
Volume 2013 (2013), Article ID 461901, 7 pages
http://dx.doi.org/10.1155/2013/461901
Research Article

Metabolic Fate of the Increased Yeast Amino Acid Uptake Subsequent to Catabolite Derepression

The Institute of Urology and Nephrology, University College London, Charles Bell House, 67 Riding House Street, London W1W 7EY, UK

Received 14 November 2012; Revised 31 December 2012; Accepted 31 December 2012

Academic Editor: Hieronim Jakubowski

Copyright © 2013 John S. Hothersall and Aamir Ahmed. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Catabolite repression (CCR) regulates amino acid permeases in Saccharomyces cerevisiae via a TOR-kinase mediated mechanism. When glucose, the preferred fuel in S. cerevisiae, is substituted by galactose, amino acid uptake is increased. Here we have assessed the contribution and metabolic significance of this surfeit of amino acid in yeast undergoing catabolite derepression (CDR). L-[U-14C]leucine oxidation was increased 15 ± 1 fold in wild type (WT) strain grown in galactose compared to glucose. Under CDR, leucine oxidation was (i) proportional to uptake, as demonstrated by decreased uptake and oxidation of leucine in strains deleted of major leucine permeases and (ii) entirely dependent upon the TCA cycle, as cytochrome c1 (Cyt1) deleted strains could not grow in galactose. A regulator of amino acid carbon entry into the TCA cycle, branched chain ketoacid dehydrogenase, was also increased 29 ± 3 fold under CCR in WT strain. Protein expression of key TCA cycle enzymes, citrate synthase (Cs), and Cyt1 was increased during CDR. In summary, CDR upregulation of amino acid uptake is accompanied by increased utilization of amino acids for yeast growth. The mechanism for this is likely to be an increase in protein expression of key regulators of the TCA cycle.