Pyruvate anaerobic metabolism

It is interesting to note that the dihydroxybenzoyl nucleus arises from chorismic acid which, in turn, is derived from erythrose phosphate and phosphoenol pyruvate, both of these substances being intermediates in the anaerobic metabolism of carbohydrate (74). Accordingly, the biogenesis of the catechol type ligand is independent of the presence of oxygen gas. 

Similarly, the regulation of PDK activity is modified in adult muscle PDC. For example, PDK activity is inhibited by pyruvate and propionate (metabolites elevated during anaerobic metabolism) and is less sensitive to stimulation by elevated NADH/NAD+ and acetyl CoA/CoA ratios (Fig. 14.2) (Thissen et al, 1986 Chen et al, 1998). The effects of NADH and acetyl CoA on PDK activity are mediated by the degree of E3-catalysed oxidation and E2-catalysed acetylation of the inner lipoyl domain of E2 (Roche and Cate, 1977 Rahmatullah and Roche, 1985, 1987 Ravindran et al, 1996 Yang et al, 1998), so that the regulation of this phenomenon is complex and involves multiple interacting components. 

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 ... 

Different abortives may be formed with alternative products or substrates. Such procedures can be useful in helping to distinguish Theorell-Chance mechanisms from ordered systems with abortive complexes . In the case of lactate dehydrogenase, the E-pyruvate-NAD+ and E-lactate-NADH abortive complexes may play a regulatory roles in aerobic versus anaerobic metabolism. 

Accumulation of metformin can occur in patients with renal insufficiency, and interference with pyruvate metabolism can lead to severe lactic acidosis. Lactic acidosis is more likely in situations associated with anaerobic metabolism, and metformin should not be given to patients with renal disease, liver disease, or severe pulmonary or cardiac disease predisposing to hypoxia. It is recommended to switch patients taking metformin to another oral hypoglycaemic prior to cardiac or other major surgery. 

Many invertebrate animals are true facultative anaerobes, able to survive for long periods, sometimes indefinitely, without oxygen.145-147 Among these are Ascaris (Fig. 1-14), oysters, and other molluscs. Succinate and alanine are among the main end products of anaerobic metabolism. The former may arise by a mixed acid fermentation that also produces pyruvate. 

All parasitic flatworms capable of anaerobic metabolism favour malate as the primary mitochondrial substrate and the oxidative decarboxylations of first malate and then pyruvate generate intramitochondrial reducing power in the form of NADH (Fig. 20.1). In contrast, the pathways used to reoxidize intramitochondrial NADH are quite diverse and depend on the stage or species of parasite under examination, but in all cases, redox balance is maintained and electron-transport associated ATP is generated by the NADH-reduction of fumarate to succinate. In the cestode, hi. diminuta, succinate and acetate are the major end products of anaerobic malate dismutation and are excreted in the predicted 2 1 ratio. In the trematode F. hepatica, succinate is then further decarboxylated to propionate with an additional substrate level phosphorylation coupled to the decarboxylation of methylmalonyl CoA. F. hepatica forms primarily propionate and acetate as end products, again in a ratio of 2 1 to maintain redox balance. 

Under anaerobic conditions, the pyruvic acid is reduced to lactic acid, which consumes the NADH produced (see Figure 12.39). Thus, anaerobic metabolism is highly inefficient, because the more energetically valuable of the two high-energy products (NADH) is consumed. 

In animal fermentations, an organic molecule (e.g., pyruvate) serves as a terminal proton and electron acceptor, forming an organic end product (e.g., lactate). In contrast, 02 is required as a terminal acceptor for the complete oxidation of substrates such as glucose, glycogen, fatty acids, or amino acids. As discussed in chapter 3, 02 was not always available as one of the substrates for oxidative metabolism and organisms in primordial times had to rely on anaerobic metabolic processes. 

The best-studied enzymes to date that contain glycyl radicals are pyruvate formate-lyase (PFL) and a ribonucleoside triphosphate reductase (ARR), both isolated from anaerobically growing E. coli. These enzymes play central roles in the anaerobic metabolism of the bacterium. The first catalyzes the reversible formation of acetyl-CoA and formate from pyruvate and coenzyme A, while the second is responsible for synthesizing the deoxyribonucleotide monomers of the polymer DNA. It is intriguing to note that formate, a product of the PFL reaction, is a substrate for the ARR. It supplies the reducing equivalents needed for each round of deoxynucleotide synthesis. ... 

Figure 14.1. Glucose Metabolism. Glucose is metabolized to pyruvate in 10 linked reactions. Under anaerobic conditions, pyruvate is metabolized to lactate and, under aerobic conditions, to acetyl CoA. The glucose-derived carbons are subsequently oxidized to CO2.

TCA cycle. (tricarboxylic acid cycle Krebs cycle citric acid cycle). A series of enzymatic reactions occurring in living cells of aerobic organisms, the net result of which is the conversion of pyruvic acid, formed by anaerobic metabolism of carbohydrates, into carbon dioxide and water. The metabolic intermediates are degraded by a combination of decarboxylation and dehydrogenation. It is the major terminal pathway of oxidation in animal, bacterial, and plant cells. Recent research indicates that the TCA cycle may have predated life on earth and may have provided the pathway for formation of amino acids. 

Lactic acidosis is one of the most common canses of high SAG metabolic acidosis. Lactic acid is the end prodnct of anaerobic metabolism of glucose (glycolysis). In normal individnals, lactic acid derived from pyruvate enters the circulation in small amonnts and is promptly removed by the liver. In the liver, and to a lesser extent in the kidney, lactic acid is reoxidized to pyruvic acid, which is then metabolized to CO2 and H2O. The normal plasma lactate concentration in healthy subjects is approximately 1 rnEq/L. " The diagnosis of lactic acidosis should be considered in aU patients with metabolic acidosis... 

Huckabee, W.E., 1961. Relationship of pyruvate and lactate during anaerobic metabolism. Am. J. Physiol. 200, 1169-1179. 

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