326 M. Ugliano and P.A. Henschke
acetate
glucose
oxalacetate
pyruvate acetaldehyde
PdcpNAD+
L-malateCO 2 ATPethanol
acetyl-CoA
citrate
L-malic
acidsuccinate
succinic
acidAdhpAldpAcs1p
CitpPyc1,2pMdhpFrdspα
α
-keto
glutarate-ketoglutaric
acidCO (^2) NADH 2
pyruvic
acid
Reductive pathway
Oxidative pathway
amino acid
OGDH biosynthesis
CO 2 NADH 2
Icdhp
CO 2
NAD+
Fig. 8D.3Metabolism of organic acids
With the exception of succinic acid, most organic acids are metabolic intermediates which
provide precursors for anabolic pathways and/or provide redox balance. Pyruvic acid, the product
of glycolysis and major source of redox during ethanol production (Fig 8D.2), is a key precursor for
anabolic and associated redox reactions, hence little is secreted.L-Malate and succinate, catalysed
by malate dehydrogenase (Mdhp) and fumarate reductase (Frdsp), respectively, are produced by
the reductive arm of the tricarboxylic acid pathway, thereby providing additional NAD+. Succinate
is excreted as succinic acid. -Ketoglutarate, a key compound for sequestering ammonia in amino
acid biosynthesis, is a product of the oxidative arm of the tricarboxylic acid pathway, being derived
from citrate, which is formed by the condensation of pyruvate derivatives oxalacetate and activated
acetate. A small amount of -ketoglutarate is secreted and surplus accumulated acid appears to be
oxidatively decarboxylated to succinate bythe glutarate dehydrogenase complex (OGDH)
by the reduction of oxalacetate catalysed by malate dehydrogenase (Mdhp), which
is derived from pyruvic acid by pyruvate carboxylase (Pyc1,2p); this step provides
oxidation of NADH (Radler 1993) (Fig 8D.3). The first step ofL-malate degrada-
tion is catalysed by malate dehydrogenasefollowed by the oxidative reactions of
the tri-carboxylic acid pathway; this pathway provides carbon skeletons for biosyn-
thetic reactions beyond pyruvic acid, when pyruvate carboxylase (Pyc1,2p) activ-
ity is low (Salmon et al. 1987). Regulation of formation/degradation is genetically