Pyruvate metabolic fate

Figure 30.11. Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals.

Pyruvate has several metabolic fates. It can be reduced to lactate, converted to oxaloacetate in a reaction important in gluconeogenesis (Chapter 15) and in an anaplerotic reaction of the TC A cycle (see below), transminated to alanine (Chapter 17), or converted to acetyl-CoA and CO2. Acetyl-CoA is utilized in fatty acid synthesis, cholesterol (and steroid) synthesis, acetylcholine synthesis, and the TCA cycle (Figure 13-6). 

Figure 27.11 Major metabolic fates of pyruvate and acetyl CoA in mammals.

In tissues other than the RBC, pyruvate has alternative metabolic fates that, depending on the tissue, include gluconeogenesis, conversion to acetyl-CoA by pyruvate dehydrogenase for further metabolism to CO in the tricarboxylic acid (TCA) cycle, transamination to alanine or carboxylation to oxaloacetate by pyruvate carboxylase (Table 23-1). In the RBC, however, the restricted enzymatic endowment precludes all but the conversion to lactate. The pyruvate and lactate produced are end products of RBC glycolysis that are transported out of the RBC to the liver where they can undergo the alternative metabolic conversions described above. 

Figure 4. Schematic representation of the metabolic fate of alanine in hepatocytes. Note that striking differences may exist between mammalian cell types on the one hand and individual amino acids on the other (see text). Solid and broken arrow lines refer to metabolic conversions and transport routes, respectively, and circles in membranes refer to specific transporters. Numbers refer to enzymes involved in alanine metabolism 1, alanine transaminase 2, pyruvate carboxylase 3, malate dehydrogenase 4, glutamate dehydrogenase 5, glutamine synthetase.

Phosphoglucomutase converts glucose-l-phosphate into glucose-6-phosphate which has several metabolic fates. It is for example a precursor in the pentose phosphate pathway (PPP), it can be converted to a-D-glucose and to pyruvate via the glycolysis pathway (see Figure 9.2). 

Alanine is the simplest L-amino acid found in protein. It has a simple metabolism, but complex physiological roles and functions. Alanine can transaminate reversibly with a-ketoglutarate, forming pyruvate and glutamate. This transamination occurs in many tissues, including liver and muscle. This is the only metabolic fate of pyruvate, other than protein synthesis. Therefore, alanine is glucogenic and is not required in the diet. 

Metabolic Fates of Pyruvate (Pyruvate/Lactate/Ethanol Metabolism)... 

Recall What are the possible metabolic fates of pyruvate ... 

Among various other metabolic fates these two adds can yield pyruvic add. 

Pyruvate oxidation together with fatty acid oxidation, is the main source of acetyl-CoA, whose main metabolic fate is the breakdown to water and carbon dioxide, through the sequence of reactions known as tricarboxylic acid (TCA) cycle, or Krebs cycle (Krebs) this cycle represents the main contributor of reducing equivalents to the mitochondrial respiratory chaia All of the enzymes of the Krebs citric acid cycle are mitochondrial. According to the majority of authors, they are located in the matrix. 

The doubly labelled sialic acids N-acetyl-[2-i4C,9-3H]neuraminic acid (NOhle and Schauer 1981) and N-glycolyl-[2-i4C,9-3H]neuraminic acid (NOhle et al. 1982) were prepared from sodium[2-i4C]pyruvate and either N-acetyl-[6-3H]mannosamine or N-glycolyl-[6- H]mannosamine, with the aid of the N-acetylneuraminate lyase from Clostridium perfringens. The metabolic fate of these compounds was studied after oral and intravenous application to mice and rats. 

An important theoretically based consideration, especially with competitive inhibitors, is that the substrates of the inhibited enzyme should not accumulate and counteract the inhibition. The biological effect of glypho-sate is aided by the multiple metabolic fates of PEP and the instability to phosphatase action of the second substrate, shikimate S-phosphate. " Similarly, pyruvate is an important constituent of the central metabolic pathways and is unlikely to reach abnormally high concentrations if ALS is inhibited. 

The fate of the oxoacid is either (i) formation of a common intermediate of metabolism, i.e. an intermediate within a well-established metabolic pathway (e.g. oxaloacetate or pyruvate, in the above examples), or (ii) conversion to a common intermediate , e.g. oxoisocaproate is converted to acetyl-CoA (see Appendix 8.3). 

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. 

The product of this metabolic sequence, pyruvate, is a metabolite of caitral importance. Its fate depends upon the conditions within a cell and upon the type of cell. When oxygen is plentiful pyruvate is usually converted to acetyl-coenzyme A, but under anaerobic conditions it may be reduced by NADH + H+ to the alcohol lactic acid (Fig. 10-3, step h). This reduction exactly balances the previous oxidation step, that is, the oxidation of glycer-aldehyde 3-phosphate to 3-phospho-glycerate (steps a and b). With a balanced sequence of an oxidation reaction, followed by a reduction reaction, glucose can be converted to lactate in the absence of oxygen, a fermentation process. The lactic acid fermentation occurs not only in certain bacteria but also in our own muscles under conditions of extremely vigorous exercise. It also occurs continuously in some tissues, e.g., the transparent lens and cornea of the eye. 

In mammals, muscle breakdown or excess protein intake results in an imbalance between the fates of the carbon chains and the amino nitrogen. Unlike fat (lipid storage) or glycogen (carbohydrate storage), excess amino acids are not stored in polymeric form for later utilization. The carbon chains of amino acids are generally metabolized into tricarboxylic acid (TCA) cycle intermediates, although it is also possible to make ketone bodies such as acetoacetate from some. Conversion to TCA intermediates is easy to see in some instances. For example, alanine is directly transaminated to pyruvate. 

A further criterion governing the fate of pyruvate is the type of cell in which it is formed, since some cells (e.g., red blood cells) lack the metabolic capability to carry out the complete oxidation of pyruvate to C02. 

What determines the fate of pyruvate produced in muscle from amino acid metabolism SOLUTION... 

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