Fumaric acid cytosolic fumarase

What is the Role of Cytosolic Fumarase in Fumaric Acid Accumulation in Rhizopus Strain ... 

According to the present suggested mechanism, fumaric acid accumulation by R. oryzae occurs mainly by a cytosolic reductive pathway converting pyruvic to fumaric acid by the successive activities of pyruvate carboxylase, malate dehydrogenase, and fumarase (Osmani and Scrutton, 1985 Kenealy et al., 1986). In the following discussion we will try to answer some of the questions that arise from this general mechanism. 

The operation of the cytosolic reductive TCA pathway for fumaric acid production in R. oryzae raises the question as to the unique role of the cytosolic fumarase in this fungus. 

It should be mentioned that with another Rhizopus strain. Ding et al. (2011) showed in cell extracts, in accordance to previous findings that lowering the urea concentrations in the medium from 2.0 to 0.1 g/L caused an increase of 300% in the cytosolic fumarase activity, accompanied with an increase in fumaric acid production. 

Based on these results, Goldberg et al. (2006) suggested two possibilities to explain these findings. The first is that in R. oryzae the cytosolic fumarase is kinetically different from the mitochondrial isoenzyme, due to distinct posttranslational modifications, or to specific conditions in the two compartments. The second possibility is that R. oryzae harbors two genes encoding two different fumarases, one in mitochondria, which catalyzes the conversion of fumaric to L-malic acid, and a cytosolic enzyme, which catalyzes the conversion of L-malic to fumaric acid. Upon transfer into medium C, a fumarase with unique characteristics is induced. L-malic acid s conversion to fumaric acid is enhanced by the induced fumarase and when the concentration of fumaric acid in the cell exceeds 2 mM, the reverse reaction to L-malic acid is fully inhibited. Thus, this property of the unique fumarase, whose existence was then only hypothesized, can ensure that fumaric acid is accumulated. 

S. cerevisiae is studied in regard to the biochemical regulation of malic acid production (Pines et al., 1996). Under environmentally stressed conditions, a small amoxmt of fumaric acid and malic acid (less than lOg/L) was produced by this common yeast. Similar to the malic acid production pathway of Aspergillus, the cytosolic reductive pathway of acid synthesis and accumulation has been shown in S. cerevisiae. A NMR study involving glucose conversions to malic acid indicates that the following reactions lead to malic acid accumulation pyruvate oxaloacetate->fumarate malate. The involvement of cytosolic fumarase in the conversion of fumaric acid to malic acid has been corroborated. Wang et al. (1988) have shown the ability of a cytoplasmic respiratory deficient mutant of S. cerevisiae to convert fumarate to malate without the participation of mitochondrial fumarase. 

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