Pyruvic Acid Catabolism

Pyruvate is catabolized aerobically. Pyruvate is catabolized anaerobically. Pyruvate is decomposed, yielding acetate, hydrogen and carbon dioxide. 

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FIGURE 25.1 The citrate-malate-pyruvate shuttle provides cytosolic acetate units and reducing equivalents (electrons) for fatty acid synthesis. The shuttle collects carbon substrates, primarily from glycolysis but also from fatty acid oxidation and amino acid catabolism. Most of the reducing equivalents are glycolytic in origin. Pathways that provide carbon for fatty acid synthesis are shown in blue pathways that supply electrons for fatty acid synthesis are shown in red. 

The next steps of glucose catabolism are called the citric acid cycle. The pyruvic acid formed in glycolysis is transported into the mitochondria, which arc subcellular organelles with double (inner and outer) membranes. They are referred to as the powerhous-... 

Reactions involve several enzymes, which have to follow in sequence for lactic acid and alcohol fermentation. This is known as the glucose catabolism pathway, with emphasis on energetic and energy carrier molecules such as ATP, ADP, NAD+ and NADH. In this pathway the six-carbon substrate yields two three-carbon intermediates, each of which passes through a sequence of reactions to the stable end product of pyruvic acid. 

Acetyl-CoA is at the product of fatty acid catabolism and may be derived from amino acids and carbohydrates (via pyruvate). Acetyl-CoA is the precursor of fatty acids, cholesterol and ketone bodies. 

Catabolic enzyme NANA aldolase catalyses cleavage of NANA to form NAM and pyruvic acid, the latter being a more attractive material for a chemoenzymatic process. It has long been known that the reverse reaction may be used for NANA synthesis. However, this approach to a manufacturing process also has complications. 

A major aim of amino acid catabolism is removal of the a-NH2 group, which results in the formation of ammonia which is then converted to urea. The removal of the a-NH2 group for most amino acids results in the formation of a carbon-compound, which is usually an oxoacid (e.g. the oxoacid for alanine is pyruvate). 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol. The mitochondrial outer membrane is freely permeable to all these compounds. Pyruvate derived from amino acid catabolism in the mitochondrial matrix, or from glucose by glycolysis in the cytosol, is converted to acetyl-CoA in the matrix. Acetyl groups pass out of the mitochondrion as citrate in the cytosol they are de-... 

These results confirmed that branched-chain amino acid catabolism via the BCDH reaction provides the fatty acid precursors for natural avermectin biosynthesis in S. avermitilis. In contrast, B. subtilis appears to possess two mechanisms for branched-chain precursor supply. The dual substrate pyruvate/branched-chain a-keto acid dehydrogenase (aceA) and an a-keto acid dehydrogenase (bfmB), which also has some ability to metabolize pyruvate, appears to be primarily involved in supplying the branched-chain initiators of long, branched-chain fatty acid biosynthesis [32,42], Two mutations are therefore required to generate the bkd phenotype in B. subtilis [31,42],... 

Answer Fatty acid catabolism increases the level of acetyl-CoA, which stimulates pyruvate carboxylase. The resulting increase in oxaloacetate concentration stimulates acetyl-CoA consumption through the citric acid cycle, causing the citrate and ATP concentrations to rise. These metabolites inhibit glycolysis at PFK-1 and inhibit pyruvate dehydrogenase, effectively slowing the utilization of sugars and pyruvate. 

The opposite process occurs during biosynthesis. Simple organic molecules such as pyruvic acid, acetyl unit or intermediate compounds of citric acid cycle serve as starting molecules for varied biosynthetic products. The energy rich molecules such as ATP or NADPH derived from catabolic reactions are utilized in the biosynthetic reactions. 

Ammonia is produced by almost all cells in the body however, only the liver has the enzymatic machinery to convert it to urea. Therefore, extra-hepatic ammonia must be transported to the liver. However, anunonia in the blood is toxic to cells, and therefore the nitrogen from amino acid catabolism is transported in blood either as glutamine or alanine. Glutamine is synthesized from Glu and ammonia in an ATP-requiring reaction that is catalyzed by glutamine synthetase. Alanine is formed from pyruvate in a transamination reaction catalyzed by alanine transaminase (ALT). 

The control of branched-chain amino acid catabolism lies within the activity of branched-chain a-keto acid dehydrogenase. This enzyme-like pyruvate dehydrogenase can occur in an active nonphosphorylated or an inactive phosphorylated form. The enzyme is phosphorylated by a specific kinase in the mitochondrion, the location of both the kinase and the branched-chain a-keto acid dehydrogenase. The kinase is inhibited by branched-chain a-keto acids thus, when these are in excess, the enzyme will be nonphosphorylated and active, allowing catabolism of the excess keto acids and, therefore, catabolism of excess branched-chain amino acids. The mitochondrion also contains a branched-chain a-keto acid dehydrogenase phosphatase, which returns the phosphorylated enzyme back to the active form. Thus, the major control of branched-chain amino-acid catabolism is the activity of the branched-chain a-keto-acid dehydrogenase, which is controlled by phosphorylation, primarily by the specific kinase, and dephosphorylation. 

Citric acid cycle electron transport and OKI dative phosphorylation fatty acid oxidation amino acid catabolism pyruvate oxidation... 

ANAEROBIC CARBOHYDRATE METABOLISM Yeasts growing in media containing high concentrations of fermentable carbohydrate invariably metabolize it fermentatively to produce ethanol and CO2. If air is present, and when the sugar concentration has been lowered, the ethanol is respired using the metabolic routes described above. Under the anaerobic conditions of a brewery fermentation the hexoses derived from wort fermentable carbohydrates are catabolized by the EMP pathway (Fig. 17.2) to pyruvic acid. The pyruvate produced is decarboxylated by the enzyme pyruvate decarboxylase, with the formation of acetaldehyde and CO2. The enzyme requires the cofactor thiamine pyrophosphate (TPP) for activity and the reaction is shown in Fig. 17.10. The acetaldehyde formed acts (in the absence of the respiratory chain) as an electron acceptor and is used to oxidize NADH with the formation of ethanol ... 

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