Glycerol dehydrogenase, mechanism

Liyanage H, S Kashket, M Young, ER Kashket (2001) Clostridium beijerinckii and Clostridium difficile detoxify methylglyoxal by a novel mechanism involving glycerol dehydrogenase. Appl Environ Microbiol 67 2004-2010. 

Insulin stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity. It increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol 3-phosphate for esterification of the newly formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue but not in liver. Insulin also—by its ability to depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and thereby reduces the concentration of... 

Understand the physiologic importance and mode of synthesis of glycerol-3-phosphate, 2,3-diphosphoglycerate, and acetyl-CoA understand the mechanism of action and regulation of pyruvate dehydrogenase with all the cofactors involved. 

Figure 7.1. Mechanism of uptake and initial enzymatic reactions in the microbial metabolism of glycerol (G). Note The gene products GlpF, GlpK, GlpD correspond to a glycerol facilitator protein, glycerol kinase, and glycerol 3-phosphate dehydrogenase, respectively.

Dehydrogenases, classified under E.C.1.1., are enzymes that catalyze reduction and oxidation of carbonyl groups and alcohols, respectively I5l The natural substrates of the enzymes are alcohols such as ethanol, lactate, glycerol, etc. and the corresponding carbonyl compounds, but unnatural ketones can also be reduced enantiose-lectively. To exhibit catalytic activities, the enzymes require a coenzyme most of the dehydrogenases use NADH or NADPH, and a few use flavin, pyrroloquinoline quinone, etc. The reaction mechanism of the dehydrogenase reduction is as follows ... 

However, a word of caution is appropriate at this point. The kinetic analysis that forms the basis of the generalization proposed by Srivastava and Bernhard is neither experimentally nor conceptually straightforward. A recent reexamination of the kinetics of NADH transfer between lactate dehydrogenase and a-glycerol-3-phosphate dehydrogenase fully supports a free-diffusion mechanism... 

Fig. 21.5. Components of the electron transfer chain. NADH dehydrogenase (complex 1) spans the membrane and has a proton pumping mechanism involving CoQ. The electrons go from CoQ to c5riochrome b-cl complex (complex El), and electron transfer does NOT involve complex II. Succinate dehydrogenase (complex II), glycerol 3-phosphate dehydrogenase, and ETF Q oxidoreductase (shown in blue) all transfer electrons to CoQ, but do not span the membrane and do not have a proton pumping mechanism. As CoQ accepts protons from the matrix side, it is converted to QH2. Electrons are transferred from complex III to complex IV (cytochrome c oxidase) by cytochrome c, a small cytochrome in the intermembrane space that has reversible binding sites on the b-c, complex and cytochrome c oxidase.

The malate—aspartate shuttle is the mechanism by which electrons from NADH produced in the cytosol are transported into mitochondria, as the inner membrane is impermeable to NADH itself. Oxaloacetate is reduced to malate in the cytosol by malate dehydrogenase, in the process oxidizing NADH to replenish cytosolic NAD. The malate-aspartate shuttle is found mainly in cardiac muscle and liver cells, while the glycerol 3-phosphate shuttle operates mainly in brain and skeletal muscle cells. Once malate has entered the mitochondria it is oxidized to oxaloacetate, generating NADH within the mitochondrial matrix. Oxaloacetate is then converted to aspartate, which is transported out of the mitochondria in exchange for glutamate. 

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