Pyruvic acid metabolism

O Kane, D. J. and Gunsalus, I. C. (1948) Pyruvic acid metabolism. A factor required for oxidation by Streptococcus faecalis. J. Bacteriol. 56, 499-506. 

In spite of the number of different structural types lipids share a common biosyn thetic origin m that they are ultimately derived from glucose During one stage of car bohydrate metabolism called glycolysis glucose is converted to lactic acid Pyruvic acid IS an intermediate... 

Compounds called carboxylic acids, which contain the -C02H grouping, occur abundantly in all living organisms and are involved in almost all metabolic pathways. Acetic acid, pyruvic acid, and citric acid are examples. 

With dimethylmalic acid lyase (EC 4.1.3.32) from Clostridium harkeri. an enzyme involved in nicotinic acid metabolism, propanoate can be added to pyruvate yielding stereospecifically the (2i ,3S)-dimethylmalic acid39. 

An intriguing stress-induced alteration in gene expression occurs in a succulent plant, Mesembryanthemum crystallinum, which switches its primary photosynthetic CO2 fixation pathway from C3 type to CAM (Crassulacean acid metabolism) type upon salt or drought stress (Winter, 1974 Chapter 8). Ostrem et al. (1987) have shown that the pathway switching involves an increase in the level of mRNA encoding phosphoenol-pyruvate carboxylase, a key enzyme in CAM photosynthesis. 

Aerobic living features metabolize sugars and fatty acids to carbon dioxide. Accordingly, there are some kinds of decarboxylation reactions. TPP-mediated decarboxylation of pyruvic acid to acetaldehyde is one of the most important steps of the metabolism of sugar compounds (Fig. 1). When the intermediate reacts with lipoic acid instead of a proton, pyruvic acid is converted to acetylcoenzyme A, which is introduced to TCA cycle (Fig. 2). 

Kung H-F, L Tsai, TC Stadtman (1971) Nicotinic acid metabolism. VIII. Tracer studies on the intermediary roles of a-methyleneglutarate, methylitaconate, dimethymaleate and pyruvate. J Biol Chem 246 6444-6451. 

During the recovery period from exercise, ATP (newly produced by way of oxidative phosphorylation) is needed to replace the creatine phosphate reserves — a process that may be completed within a few minutes. Next, the lactic acid produced during glycolysis must be metabolized. In the muscle, lactic acid is converted into pyruvic acid, some of which is then used as a substrate in the oxidative phosphorylation pathway to produce ATP. The remainder of the pyruvic acid is converted into glucose in the liver that is then stored in the form of glycogen in the liver and skeletal muscles. These later metabolic processes require several hours for completion. 

The authors chose pyruvic acid as their model compound this C3 molecule plays a central role in the metabolism of living cells. It was recently synthesized for the first time under hydrothermal conditions (Cody et al., 2000). Hazen and Deamer carried out their experiments at pressures and temperatures similar to those in hydrothermal systems (but not chosen to simulate such systems). The non-enzymatic reactions, which took place in relatively concentrated aqueous solutions, were intended to identify the subsequent self-selection and self-organisation potential of prebiotic molecular species. A considerable series of complex organic molecules was tentatively identified, such as methoxy- or methyl-substituted methyl benzoates or 2, 3, 4-trimethyl-2-cyclopenten-l-one, to name only a few. In particular, polymerisation products of pyruvic acid, and products of consecutive reactions such as decarboxylation and cycloaddition, were observed the expected tar fraction was not found, but water-soluble components were found as well as a chloroform-soluble fraction. The latter showed similarities to chloroform-soluble compounds from the Murchison carbonaceous chondrite (Hazen and Deamer, 2007). 

The results obtained appeared quite promising, but the real sensation was the detection of pyruvate, the salt of 2-oxopropanoic acid (pyruvic acid), which is one of the most important substances in contemporary metabolism. Pyruvic acid was first obtained in 1835 by Berzelius from dry distillation of tartaric acid. The labile pyruvate was detected in a reaction mixture containing pure FeS, 1-nonanethiol and formic acid, using simulated hydrothermal conditions (523 K, 200 MPa). The pyruvate yield, 0.7%, was certainly not overwhelming, but still remarkable under the extreme conditions used, and its formation supports Wachtershauser s theory. Cody concludes from these results that life first evolved in a metabolic system prior to the development of replication processes. 

Thiamine catalyzes decarboxylations, as of pyruvic acid and trans-ketolations in carbohydrate metabolism. Free thiamine is carried by the... 

The clinical significance of thiamine and its necessity for pyruvic acid oxidation has been discussed. Recent reports concerning the coenzyme function of thiamine in pentose (H13), tryptophan (D2), and lipoic acid metabolism (R6) have increased our knowledge of thiamine in metabolism and lend added interest to the role of thiamine in clinical problems. This method has also been used to assay thiamine in liver and brain. 

The conversion of glucose proceeds via its splitting into pyruvic acid and hydrogen, which is bound as NADPH. Pyruvic acid is subsequently decarboxylated to C02 and acetaldehyde (bound to the coenzyme-A), which is subsequently rehydrogenated to ethanol. The overall reaction delivers therefore two molecules of ethanol and two C02 for every glucose unit. Notice that such a simplified metabolic pathway does not display the energy fluxes, e.g., in the form of ATP/ADP interconversion. 

The metabolic pathways can be diverted to other products, however. For instance, the pyruvic acid can be rehydrogenated to lactic acid. Accordingly, glucose is converted into two molecules of lactic acid, which is the building block for Cargill s polylacate polymer [65],... 

Anker,3 5 using isotope tracer technique, found in a mixed laboratory strain of rats (Wistar) no significant conversion of pyruvic acid to acetic acid. This was in contrast to the results obtained with the Sprague-Dawley strain of rats in which either such a conversion did take place or else pyruvic acid was utilized directly for acetylation. Exactly what constitutes the enzymic difference between the two strains is not known, but it is clear that a striking and potentially important difference exists. From the genetic standpoint one should not expect precisely the same metabolic results from rats of different strains or even from individual rats within the same strain, but the difference here reported is perhaps more fundamental than one might anticipate. If this difference is real, presumably other differences exist which have not been looked for, and one should be extremely careful about accepting the results from one strain as applicable to another. 

However interesting, this example is a highly specific one with little extrapolative value. Indeed, only a very few closely similar analogues, e.g., 5-fluoro-5,6-dihydrouracil, were found to be substrates for AlaAT-II. Thus, /3-chloro-L-alanine was metabolized to pyruvic acid, but it slowly inactivated the enzyme [76]. 

Pantothenic acid CoA i Fatty acid synthase Fatty acyl CoA synthetase Pyruvate dehydrogenase ci-Ketoglutarate dehydrogenase Fatty acid metabolism PDH TCA cycle Rare... 

Biochemical reactions include several types of decarboxylation reactions as shown in Eqs. (1)-(5), because the final product of aerobic metabolism is carbon dioxide. Amino acids result in amines, pyruvic acid and other a-keto acids form the corresponding aldehydes and carboxylic acids, depending on the cooperating coenzymes. Malonyl-CoA and its derivatives are decarboxylated to acyl-CoA. -Keto carboxylic acids, and their precursors (for example, the corresponding hydroxy acids) also liberate carbon dioxide under mild reaction conditions. 

Thiamine pyrophosphate is a coenzyme for several enzymes involved in carbohydrate metabolism. These enzymes either catalyze the decarboxylation of oi-keto acids or the rearrangement of the carbon skeletons of certain sugars. A particularly important example is provided by the conversion of pyruvic acid, an oi-keto acid, to acetic acid. The pyruvate dehydrogenase complex catalyzes this reaction. This is the key reaction that links the degradation of sugars to the citric acid cycle and fatty acid synthesis (chapters 16 and 18) ... 

Once the phosphate ester is hydrolysed, there is an immediate rapid tautomerism to the keto form, which becomes the driving force for the metabolic transformation of phosphoenolpyruvic acid into pyruvic acid, and explains the large negative free energy change in the transformation. This energy release is coupled to ATP formation (see Box 7.25). 

The glycolytic pathway, or glycolysis, is a metabolic sequence in which glucose is broken down to pyruvic acid. The subsequent fate of pyruvate then depends upon whether or not the organism is aerobic or anaerobic Under aerobic conditions, pyruvate is oxidized via oxidative phosphorylation under anaerobic conditions, pyruvate is converted further into compounds such as lactate or ethanol, depending upon the organism. 

Acetylmethylcarbinol has also been recognized as a product of the metabolism of animal cells and its origin from sugar by way of pyruvic acid and acetaldehyde has been demonstrated. It therefore appears probable that 2,3-butylene glycol, which together with acetylmethylcarbinol... 

Figure 21. Secondary metabolism blocks and amino acid derivation. Note that shikimic acid can be derived directly from photosynthesis and glycolysis through the pentose phosphate cycle, or alternatively as a pyruvic acid postcursor.

Acid-base and electrolyte balance High therapeutic dose especially when used in rheumatic fever, stimulates respiration and causes respiratory alkalosis. Reduction in bicarbonate and potassium level reduces the buffering capacity of the extracellular and intracellular fluid. Hypokalemia may lead to dehydration and hypernatremia. They also interfere with carbohydrate metabolism resulting in accumulation of pyruvic acid and lactic acid. 

---