2- Oxoglutarate

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

Oxoglutaric acid (2-oxopentane-l,5-dioic, a-ketoglutaric acid) [328-50-7] M 146.1, m 114 , 115-117 , (pK ,( see oxaloacetic acid above). Crystd repeatedly from Me2CO/ benzene, EtOAc or ethyl propionate. 

Adenine nucleotides Phosphate (P7) Dicarboxylates/P " exchange 2-Oxoglutarate/malate exchange Pyruvate... 

The metabolism of amino acids is complex and is described in standard text books. These are usually converted by aminotransferases to the corresponding 2-oxoacids which are partly oxidized in the matrix of muscle mitochondria and partly exported to the liver. Glutamate and aspartate yield 2-oxoglutarate and oxaloacetate, respectively, which enter the citrate cycle directly, and other 2-... 

Figure 4. The citrate cycle. There is complete oxidation of one molecule of acetyl-CoA for each turn of the cycle CH3COSC0A + 2O2 - 2CO2 + H2O + CoASH. The rate of the citrate cycle is determined by many factors including the ADP/ATP ratio, NAD7NADH ratio, and substrate concentrations. During muscle contraction, Ca is released from cellular stores (mainly the sarcoplasmic reticulum) and then taken up in part by the mitochondria (see Table 2). Ca " activates 2-oxoglutarate and isocitrate dehydrogenases (Brown, 1992). Succinate dehydrogenase may be effectively irreversible. Enzymes ...

Dorner E, M Boll (2002) Properties of 2-oxoglutarate ferredoxin oxidoreductase from Thauera aromatica and its role in enzymatic reduction of the aromatic ring. J Bacterial 184 3975-3983. 

Ebenau-Jehle, M Boll, G Fuchs (2003) 2-oxoglutarate NADP oxidoreductase m Azoarcus evansii properties and function in electron transfer reactions in aromatic ring reduction. J Bacterial 185 6119-6129. 

Fig. 5.7. In green sulfur bacteria and in some archaebacteria, a reverse citric acid cycle is used for the assimilation of C02. It must be assumed that this was the original function of the citric acid cycle that only secondarily took over the role as a dissimulatory and oxidative process for the degradation of organic matter. A major enzyme here is 2-oxoglutarate ferredoxin for C02 fixation. Note that it, like several other enzymes in the cycle, uses Fe/S proteins. One is the initial so-called complex I which has eight different Fe/S centres of different kinds but no haem (see also other early electron-transfer chains, e.g. in hydrogenases).

Turnbull JJ, Nakajima J, Welford RW, Yamazaki M, Saito K and Schofield CJ. 2004. Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis anthocyanidin synthase, flavonol synthase, and flavanone 33-hydroxylase. J Biol Chem 279 1206-1216. 

Sensitive flow-injection analyses of aspartate, glutamate, 2-oxoglutarate, and oxaloacetate were developed using immobilized bacterial luciferase enzymes. 

The first suggestion that substrates in carbohydrate oxidation might exert catalytic effects on the oxidation of other intermediates (cf.earlier demonstration of such action in the urea cycle by Krebs and Henseleit, 1932 see Chapter 6) arose from the work of Szent-Gyorgi (1936). He demonstrated that succinate and its 4C oxidation products catalytically stimulated the rate of respiration by muscle tissues. He also observed that reactions between the 4C intermediates were reversible and that if muscle was incubated with oxaloacetate, fumarate and malate made up 50-75% of the products, 2-oxoglutarate 10-25% and, significantly, 1-2% of the C was converted to citrate. These observations were... 

When his studies on carbohydrate oxidation restarted in Sheffield, Krebs experiments included studies on the anaerobic dismutation of pyruvate by bacteria and various animal tissues. Assuming the role for the dicarboxylic acids postulated by Szent-Gyorgi, the main question was the route by which the carbon atoms of pyruvate were converted to succinate. In May 1936 Krebs had observed that if 2-oxoglutarate was added to pyruvate, the yield of succinate was enormously increased. In his notebook written that year (Holmes, 1993) Krebs postulated ... 

In the next 2 to 3 years further experiments, particularly by Eggleston, who had joined Krebs in January 1936, confirmed and extended the observations. Careful quantitative evaluation of the data indicated that citrate like fumarate (Szent-Gyorgi) and like ornithine in the urea cycle exerted a catalytic effect on muscle metabolism. If arsenite, which blocks 2-oxoglutarate oxidation, was added with citrate to a respiring pigeon-muscle preparation, 2-oxoglutarate accumulated. 

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