Fine control of the conversion of pyruvate (phosphoenolpyruvate) to oxaloacetate in various species

Regulation of pyc1 encoding pyruvate carboxylase isozyme I by nitrogen sources in Saccharomyces cerevisiae

“…Our findings on the specific control of PYC1 and the lack of apparent control of PYC2 by the nitrogen source may support an idea put forward by Scrutton some 20 years ago [1]. Taking into account the kinetic differences and the different localization of the yeast pyruvate carboxylase with respect to the mammalian enzyme, Scrutton [1] proposed that the yeast pyruvate carboxylase may have a biosynthetic function rather than an anaplerotic role.…”

“…The repressive effect may be explained considering that the amino acids of the first group directly supply the central metabolism with oxaloacetate, which could reduce the carbon flow through pyruvate carboxylase. However, the positive effect exerted by the second group of amino acids could be a consequence of their entrance in the central metabolism at the level of pyruvate or acetyl-CoA, which are, respectively, the substrate and a potent activator of the pyruvate carboxylase [1,2]. It is not easy to explain the effect caused by threonine and methionine assimilation by oxidative deamination [23±26], which releases NH4…”

“…It catalyses the magnesium±ATP-and biotindependent carboxylation of pyruvate to oxaloacetate, a reaction necessary for the replenishment of the tricarboxylic cycle in all eukaryotic organisms [1,2]. This key function justifies the fine metabolic control of this enzyme by different effectors, including activators such as acetyl-CoA and palmitoyl-CoA and inhibitors such as aspartate [1±3].…”

“…The physiological significance of the two genes is not yet clear, because even if both genes are expressed slightly differently depending on the growth phase of yeast cultures on glucose or on the carbon source of the medium, the differences appear minor as to physiological relevance [6,7]. It is also noteworthy that the two pyruvate carboxylase isoenzymes are localized in the cytosol [8±10], whereas in mammalian cells, this enzyme is associated with the mitochondrion, a localization which appears more befitting with its function of replenishing the mitochondrially localized tricarboxylic acid cycle [1].…”

“…As oxaloacetate, the product of pyruvate carboxylase, is the direct precursor of C4-amino acids and is implicated in purine and protein synthesis [1,2,11], it seems plausible to expect that the expression of the PYC genes could be influenced by the nature of the nitrogen source present in the growth medium. In fact, in 1975, Haarasilta and Oura [12] showed that, in S. cerevisiae, the substitution of ammonium ions for aspartate or asparagine in a glucose mineral medium caused a three-to fourfold decrease in the activity of pyruvate carboxylase.…”