α-Ketoglutarate-dependent Oxidation of Glyoxylic Acid in Rat-liver Mitochondria*

Alternate pathways of metabolism of short-chain fatty acids.

“…In the latter organism, a-keto j3-hydroxyadipate was decarboxylated to a-hydroxyglutarate and then oxidized to regenerate a-ketoglutarate. Similar reactions occur in rat liver mitochondria (76).…”

Carboligase activity of α-ketoglutarate dehydrogenase

“…Koch and Stockstad (1965) suggested that KG and glyoxylate condensed to form 2-hydroxy-3-ketoadipic acid (HKA) which was then decarboxylated to HKV by acid. The establishment of DHKP as another product of the KG plus glyoxylate condensation shows that the initial product is undoubtedly 2-hydroxy-3-ketoadipic acid rather than 2,3-dihydroxyadipic acid (Kawasaki et al, 1966). This intermediate can then be decarboxylated to HKV or it can react with another molecule of glyoxylate to form DHKP.…”

Isolation and identification of 5-hydroxy-4-ketovaleric acid as a product of α-ketoglutarate:glyoxylate carboligase

“…Using similar techniques, Okuyama et al ( 1965) demonstrated an analogous reaction with extracts of Rhodopseudomonas spheroides and further postulated a cyclic mechanism for the oxidation of glyoxylate involving 2-keto-3-hydroxyadipic acid and -hydroxyglutarate. A similar system was found in rat liver mitochondria (Kawasaki et al, 1966). Recently, Koch and Stockstad (1965) reported partial purification from rat liver mitochondria of an enzyme, glyoxylate carboligase, which catalyzed the synergistic decarboxylation of glyoxylate and -ketoglutarate.…”

“…When glyoxylate-l,2-14C (ten vessels, 48,000 cpm/ vessel) was incubated, a total of 266,000 cpm was found in 14CG2 and 235,000 cpm was found in the perchloric acid filtrates. It had been previously demonstrated in R. spheroides (Okuyama et al, 1965), rat liver mitochondria (Kawasaki et al, 1966), and pig liver mitochondria (Stewart and Quayle, 1967) that glyoxylate-l-14C but not glyoxylate-2-14C yielded I4C02 when incubated with -ketoglutarate. Since our system produced approximately equal molar amounts of radioactivity in 14C02 and in the perchloric acid filtrate from glyoxylate-1,2-14C, it was assumed that the carbon dioxide was derived almost entirely from the carboxyl carbon of glyoxylate while the -carbon was incorporated into some water-soluble intermediate(s).…”

“…Koch and Stockstad (1965) suggested that glyoxylate and a-ketoglutarate undergo an initial condensation to yield 2hydroxy-3-ketoadipic acid which then decarboxylates to HKV in the presence of acid. Kawasaki et al (1966) have suggested that in rat liver mitochondria the initial condensation product is 2-keto-3-hydroxyadipic acid which could be converted enzymatically to a-hydroxyglutaric acid. These alternate possibilities are shown in Figure 2.…”