Metabolism of pyruvate

The citrate cycle is the final common pathway for the oxidation of acetyl-CoA derived from the metabolism of pyruvate, fatty acids, ketone bodies, and amino acids (Krebs, 1943 Greville, 1968). This is sometimes known as the Krebs or tricarboxylic acid cycle. Acetyl-CoA combines with oxaloacetate to form citrate which then undergoes a series of reactions involving the loss of two molecules of CO2 and four dehydrogenation steps. These reactions complete the cycle by regenerating oxaloacetate which can react with another molecule of acetyl-CoA (Figure 4). 

The majority of microbial hydrogen production is driven by the anaerobic metabolism of pyruvate, formed during the catabolism of various substrates. The breakdown of pyruvate is catalyzed by one of two enzyme systems ... 

As noted earlier, coenzymes are frequently altered structurally in the course of an enzymatic reaction. However, they are usually reconverted to their original structure in a subsequent reaction, as opposed to being further metabolized. One turn of the citric acid cycle converts NAD+ into NADH, FAD into FADH2, and acetyl-SCoA into CoASH. Coenzyme A is consumed in the metabolism of pyruvate (see below) but regenerated in the citric acid cycle. Both NADH and FADH2 are reconverted into NAD+ and FAD by the electron transport chain. 

Amino-4-cyclopropylidenebutanoic acid (2S)-56, is a methylenecyclopro-pane substituted alanine which can be considered as a non-natural isomer of hypoglycine A 51. It has recently been synthesized racemic [61] and enantiome-rically pure [62]. Biological assays have shown that at relatively high concentration the 5,6-methanoamino acid 56 inhibits the metabolism of pyruvate into glucose, but 56 is not active in inducing the mitochondrial oxidation of fatty acids,Eq. (21) [63]. 

The further metabolism of pyruvate also yields ATP synthesis through oxidative phosphorylation (see Chapter 7). 

C. In cells that are unable to transfer electrons to oxygen due to lack of mitochondria, eg, RBCs, or in vigorously exercising muscle cells (anaerobic conditions), NAD" is regenerated by further metabolism of pyruvate. 

S ATP -P acetate <1-18> (<8> acetate kinase/phosphotransacetylase, major role of this two-enzyme sequence is to provide acetyl coenzyme A which may participate in fatty acid synthesis, citrate formation and subsequent oxidation [1] <3> function in the metabolism of pyruvate or synthesis of acetyl-CoA coupling with phosphoacetyltransacetylase [15] <11> function in the initial activation of acetate for conversion to methane and CO2 [19] <10> key enzyme and responsible for dephosphorylation of acetyl phosphate with the concomitant production of acetate and ATP [30]) (Reversibility r <1-18> [1, 2, 5-21, 24-27, 29-33]) [1, 2, 5-21, 24-27, 29-33]... 

The further metabolism of pyruvate or PEP is still under investigation. Increasing support is available for the view that the C3 residue from decarboxylation is converted, by a reversal of glycolysis, into a storage carbohydrate which later serves... 

Creasey Do you agree that half the total metabolism of pyruvate goes through the GABA shunt, and if it does, do you think that it is reasonable to suggest as an important transmitter a compound having such a vigorous metabolic role ... 

Many reactions involved in this pathway are omitted. The point of origin of the glucuronic acid cycle from UDPG is indicated (see Fig. 3). The metabolism of pyruvate may proceed in any of several different directions, viz., amino acids, fatty acids, sterols, steroids, and the tricarboxylic acid cycle. Specific enzymes catalyze each conversion indicated by arrows. Broken arrows indicate that several steps are involved. 

Recall Which steps of aerobic metabolism of pyruvate through the citric acid cycle are control points ... 

The influence of the adrenal hormones and of insulin on the metabolism of pyruvate and glucose by rat diaphragm muscle has been studied by Villee et al. (1952), who proposed (1) that the adrenal hormones inhibit hexokinase, as postulated by Colowick et al. (1947) (2) that the absence of the adrenals inhibited the conversion of glucose-6-phosphate to glycogen and (3) that some step in the condensation of pyruvate with oxaloacetate was accelerated by insulin and retarded by the adrenal hormones. The latter point was based in part on the observation that, in muscle from adrenalectomized rats, lactic acid production was decreased and the oxidation of pyruvate to CO2 was increased. All these suggestions... 

A racemase brings about inversion of the relatively cheap (L)-isomers of alanine or aspartic acid, but not of (D)-phenylalanine. Only (L)-phenylalanine is deaminated by an (L)-amino acid deaminase, whereas (D)-phenylalanme is not. The latter is generated by ammonia transfer from (D)-alanine or (D)-aspar-tic acid with a (D)-amino acid aminotransferase. The equilibria are moved in favour of the product, either by the metabolism of pyruvic acid or oxosuccinic acid. Since (L)-amino acid deaminases, like (D)-amino add aminotransferases, are non-specific, they also permit the preparation of a variety of other (D)-amino acids. [58]... 

---