Dehydrogenase reactions

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

FIGURE 16.10 Formation of a covalent intermediate in the glyceraldehyde-3-phos-phate dehydrogenase reaction. Nucleophilic attack by a cysteine —SH group forms a covalent acylcysteine intermediate. Following hydride transfer to NAD, nucleophilic attack by phosphate yields the product, 1,3-bisphosphoglycerate. 

The substrates of catabolism—proteins, carbohydrates, and lipids—are good sources of chemical energy because the carbon atoms in these molecules are in a relatively reduced state (Figure 18.9). In the oxidative reactions of catabolism, reducing equivalents are released from these substrates, often in the form of hydride ions (a proton coupled with two electrons, H ). These hydride ions are transferred in enzymatic dehydrogenase reactions from the substrates... 

FIGURE 18.10 Hydrogen and electrons released in the course of oxidative catabolism are transferred as hydride ions to the pyridine nucleotide, NAD, to form NADH -t- H in dehydrogenase reactions of the type... 

FIGURE 19.18 A mechanism for the glycer-aldehyde-3-phosphate dehydrogenase reaction. Reaction of an enzyme snlfliydryl with the carbonyl carbon of glyceraldehyde-3-P forms a thiohemiacetal, which loses a hydride to NAD to become a thloester. Phosphorolysls of this thloester releases 1,3-blsphosphoglycerate. 

FIGURE 19.30 (a) Pyruvate reduction to ethanol in yeast provides a means for regenerating NAD consumed in the glyceraldehyde-3-P dehydrogenase reaction, (b) In oxygen-depleted muscle, NAD is regenerated in the lactate dehydrogenase reaction. 

How might iodoacetic acid affect the glyceraldehyde-3-phosphate dehydrogenase reaction in glycolysis Justify your answer. 

The mechanism of the pyruvate dehydrogenase reaction is a tour de force of mechanistic chemistry, involving as it does a total of three enzymes (a) and five different coenzymes—thiamine pyrophosphate, lipoic acid, coenzyme A, FAD, and NAD (b). 

FIGURE 20.10 (a) The isocitrate dehydrogenase reaction, (b) The active site of isocitrate dehydrogenase. Isocitrate is shown in green, NADP is shown in gold, with Ca" in red. 

FIGURE 20.14 The succinate dehydrogenase reaction. Oxidation of succinate occurs with reduction of [FAD]. Reoxidation of [FADH9] transfers electrons to coenzyme Q. 

Note that flavin coenzymes can carry out either one-electron or two-electron transfers. The succinate dehydrogenase reaction represents a net two-electron reduction of FAD. 

A typical intramitochondrial concentration of malate is 0.22 mM. If the [NAD ]/[NADH] ratio in mitochondria is 20 and if the malate dehydrogenase reaction is at equilibrium, calculate the intramitochondrial concentration of oxaloacetate at 25°C. 

The first step of the u-ketoglntarate dehydrogenase reaction involves decarboxylation of the substrate and leaves a covalent TPP intermediate. Write a reasonable mechanism for this reaction. 

Based on the action of thiamine pyrophosphate in catalysis of the pyruvate dehydrogenase reaction, suggest a suitable chemical mechanism for the pyruvate decarboxylase reaction in yeast ... 

This is the isocitrate dehydrogenase reaction of the TCA cycle. Writing the two half-cell reactions, we have... 

FIGURE 21.V The fatty acyl-CoA dehydrogenase reaction, emphasizing that the reaction involves reduction of enzyme-bonnd FAD (indicated by brackets). 

Calculate the value of A l,/ for the glyceraldehyde-3-phos-phate dehydrogenase reaction, and calculate the free energy change for the reaction under standard-state conditions. 

FIGURE 23.27 The glucose-6-phosphate dehydrogenase reaction is the committed step in the pentose phosphate pathway. 

FIGURE 24.11 The acyl-CoA dehydrogenase reaction. The two electrons removed in this oxidation reaction are delivered to the electron transport chain in the form of reduced coenzyme Q (UQH9). 

Figure 29-5. The i-glutamate dehydrogenase reaction. NAD(P) means that either NAD or NADP can serve as co-substrate. The reaction is reversible but favors glutamate formation.

Mutation of the dihydrolipoate reductase component impairs decarboxylation of branched-chain a-keto acids, of pyruvate, and of a-ketoglutarate. In intermittent branched-chain ketonuria, the a-keto acid decarboxylase retains some activity, and symptoms occur later in life. The impaired enzyme in isovaleric acidemia is isovaleryl-CoA dehydrogenase (reaction 3, Figure 30-19). Vomiting, acidosis, and coma follow ingestion of excess protein. Accumulated... 

The role of the iron-sulphur system of xanthine oxidase in the catalytic reaction is somewhat problematical. Nevertheless, it is clear, both from rapid freezing EPR (53) and from stopped-flow measurements monitored optically at 450 nm (58, 63) (where both iron and flavin are measured), that iron is reduced and oxidized at catalytically significant rates. Perhaps the best interpretation is that it functions as a store for reducing equivalents within the enzyme when this is acting as an oxidase, though it may well represent the main site of electron egress in dehydrogenase reactions (52). 

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