LEU2 encodes beta-isopropylmalate dehydrogenase, the enzyme that catalyzes the third step in leucine biosynthesis (shown here), the conversion of beta-isopropylmalate into alpha-ketoisocaproate (2). In contrast to most of the enzymes involved in the superpathway of branched-chain amino acid (valine, leucine, isoleucine) biosynthesis, which are mitochondrial, Leu2p localizes to the cytoplasm (3). Like the other genes in the leucine biosynthesis pathway, LEU2 is transcriptionally repressed in the presence of leucine (4, 5). However, the major regulatory mechanism of LEU2 expression is mediated by the dual regulator Leu3p and its co-activator alpha-isopropylmalate, an upstream intermediate in leucine biosynthesis (6). Leu3p binds to an upstream activation signal in the LEU2 promoter irrespective of the presence or absence of alpha-isopropylmalate, but in its presence Leu3p upregulates LEU2 transcription while in its absence Leu3p represses transcription (6). In cells lacking Leu3p, the transcriptional activator Gcn4p is required for basal levels of LEU2 expression (6). Additionally, LEU2 transcription is upregulated in a dose-dependent manner by the transcription factor Mot3p, which also mediates repression of pheromone-induced gene expression (7).

Although leu2 null mutants are viable, leu2 is synthetically lethal in combination with the amino acid sensor and transport genes ssy1, ptr3, and bap2 (8). Leu2p is very sensitive to low temperatures and dilution when removed from the cellular environment but intact yeast cells can be stored frozen for months without loss of dehydrogenase activity (9).

Last updated: 2005-10-14