Pyruvate dehydrogenase phosphate phosphatase

Pyruvate dehydrogenase phosphate phosphatase is stimulated by Ca. In muscles, the Ca + concentration increases dramatically during muscle contraction. How would the elevated Ca + concentration affect the rate of glycolysis and the citric acid cycle ... 

A cell is deficient in pyruvate dehydrogenase phosphate phosphatase. How would such a deficiency affect cellular metabolism ... 

ATP is an important source of energy for muscle contraction. Pyruvate dehydrogenase phosphate phosphatase is activated by calcium ion, which increases greatly in concentration during exercise. Why is activation of the phosphatase consistent veith the metabolic requirements of muscle during contraction ... 

Pyruvic and lactic acids Pyruvate decarboxylase EC4.1.1.1) Pyruvate dehydrogenase phosphate phosphatase (EC 1.2.3.3), Dihydrolipoyl dehydrogenase (ECl.6.4.3) 15.4... 

The regulatory role of calcium ions in intermediary metabolism is well documented. Calcium has been shown to be involved in activation or inhibition of specific enzyme systems [105], For example, it activates cyclic nucleotide phosphodiesterase, phosphofructokinase, fructose 1 6 biphosphatase, glycerol phosphate dehydrogenase, pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase. Calcium ions inhibit pyruvate kinase, pyruvate carboxylase, Na+/K+-AT-Pase and adenylate cyclase. 

Control of the activity of the pyruvate dehydrogenase complex is exerted by the phosphorylation of pyruvate decarboxylase (E[), which renders it inactive. This process is catalyzed by pyruvate dehydrogenase kinase, which is always tightly bound to E[. The kinase is activated by high-energy conditions, and it requires ATP to accomplish the phosphorylation step. Another enzyme, phosphoprotein phosphatase, is weakly bound to E, and reactivates the system by removing the inhibitory phosphate group (Fig. 12-8). 

Fig. 20.16. Regulation of pyruvate dehydrogenase complex (PDC). PDC kinase, a subunit of the enzyme, phosphorylates PDC at a specific serine residue, thereby converting PDC to an inactive form. The kinase is inhibited by ADP and pyruvate. PDC phosphatase, another subunit of the enzyme, removes the phosphate, thereby activating PDC. The phosphatase is activated by Ca ". When the substrates, pyruvate and CoASH, are bound to PDC, the kinase activity is inhibited and PDC is active. When the products acetyl CoA and NADH bind to PDC, the kinase activity is stimulated, and the enzyme is phosphorylated to the inactive form. E] and the kinase exist as tissue-specific isozymes with overlapping tissue spiecificity, and somewhat different regulatory properties.

Five enzymes are involved in the pyruvate dehydrogenase complex of mammals. Pyruvate dehydrogenase transfers a two-carbon unit to TPP and releases CO. Dihydrolipoyl transacetylase transfers the two-carbon acetyl unit to lipoic acid and then to coenzyme A. Dihydrolipoyl dehydrogenase reoxidizes lipoic acid and reduces NAD" to NADH. Pyruvate dehydrogenase kinase phosphorylates PDH. PDH phosphatase removes the phosphate. Lipoic acid plays a role both in redox and in acetyl-transfer reactions. 

Figure 5 Model of phosphorus (P) deficiency-induced physiological changes associated with the release of P-mobilizing root exudates in cluster roots of white lupin. Solid lines indicate stimulation and dotted lines inhibition of biochemical reaction sequences or mclaholic pathways in response to P deliciency. For a detailed description see Sec. 4.1. Abbreviations SS = sucrose synthase FK = fructokinase PGM = phosphoglueomutase PEP = phosphoenol pyruvate PE PC = PEP-carboxylase MDH = malate dehydrogenase ME = malic enzyme CS = citrate synthase PDC = pyruvate decarboxylase ALDH — alcohol dehydrogenase E-4-P = erythrosc-4-phosphate DAMP = dihydraxyaceConephos-phate APase = acid phosphatase.

Control of pymvate dehydrogenase activity is via covalent modification a specific kinase causes inactivation of the PDH by phosphorylation of three serine residues located in the pyruvate decarboxylase/dehydrogenase component whilst a phosphatase activates PDH by removing the phosphates. The kinase and phosphatase enzymes are non-covalently associated with the transacetylase unit of the complex. Here again we have an example of simultaneous but opposite control of enzyme activity, that is, reciprocal regulation. 

Fig. 11. Chemo-enzymic synthesis of the sialyl Le sequence [541]. NMK, nucleoside-monophosphate kinase PEP, phosphoenolpyruvate PK, pyruvate kinase PPase, inorganic phosphatase Pi, phosphate PPi, pyrophosphate PYR, pyruvate TADH, Thermoanaerobium broddi alcohol dehydrogenase.

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