Dihydroxyacetone phosphate, from glycerol

Reduction of dihydroxyacetone phosphate (DHAP) from glycolysis by glycerol 3-P dehydrogenase, an enzyme in both adipose tissue and liver... 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Another pathway is the L-glycerol 3-phosphate shuttle (Figure 11). Cytosolic dihydroxyacetone phosphate is reduced by NADFl to s.n-glycerol 3-phosphate, catalyzed by s,n-glycerol 3-phosphate dehydrogenase, and this is then oxidized by s,n-glycerol 3-phosphate ubiquinone oxidoreductase to dihydroxyacetone phosphate, which is a flavoprotein on the outer surface of the inner membrane. By this route electrons enter the respiratory chain.from cytosolic NADH at the level of complex III. Less well defined is the possibility that cytosolic NADH is oxidized by cytochrome bs reductase in the outer mitochondrial membrane and that electrons are transferred via cytochrome b5 in the endoplasmic reticulum to the respiratory chain at the level of cytochrome c (Fischer et al., 1985). 

Glycerol phosphate comes from glycerol (not in adipose) or from dihydroxyacetone phosphate (in liver and adipose). Nitrogen-containing phospholipids are made from diglyceride. Other phospholipids are made from phosphatidic acid. 

Fatty acids are both stored in and exported from the liver as triglycerides. The carbon atoms for the glycerol backbone of triglycerides are also derived from glucose by a diversion of dihydroxyacetone phosphate from glycolysis (Figures 6.16 and 6.17). 

Fessner, W.D., and Sinerius, G., Synthesis of dihydroxyacetone phosphate (and isosteric analogues) by enzymatic oxidation sugars from glycerol. Angew. Chem. bit. Ed. Engl, 1994, 33, 209. 

Glycerol 3-phosphate can arise in two ways, either (i) from glycerol, via the enzyme glycerol kinase or (ii) from dihydroxyacetone phosphate, which is produced in glycolysis, by reduction with NADH, catalysed by glycerol-3-phosphate dehydrogenase ... 

FIGURE 21-21 Glyceroneogenesis. The pathway is essentially an abbreviated version of gluconeogenesis, from pyruvate to dihydroxyacetone phosphate (DHAP), followed by conversion of DHAP to glycerol 3-phosphate, which is used for the synthesis of triacylglycerol. 

Fate of glycerol Glycerol that is released from triacylglycerol used almost exclusively by the liver to produce glycerol 3-phc phate, which can enter either glycolysis or gluconeogenesis oxidation to dihydroxyacetone phosphate (see p. 188). 

Breakdown The fatty acids in triacylglycerols are released from the glycerol backbone by the action of lipases. The free fatty acids can then be degraded by (3-oxidation to produce energy. The glycerol is converted into dihydroxyacetone phosphate which enters glycolysis. 

The oxidation of L-glycerol 3-phosphate to dihydroxyacetone phosphate is catalyzed by two different enzymes. One is the cytoplasmic NAD-linked a-glycerophosphate dehydrogenase, and the other is the mitochondrial enzyme, which appears to contain flavin and iron. The latter enzyme was first studied by Green in 1936 (223). It was shown to be associated with respiratory particles, and widely distributed in animal tissues. The highest concentration of the enzyme was found in the brain. Lardy and co-workers (234) studied the enzyme in deoxycholate-solubilized particles obtained from skeletal muscle, confirmed the finding... 

Figure 18.37. Glycerol 3-Phosphate Shuttle. Electrons from NADH can enter the mitochondrial electron transport chain by being used to reduce dihydroxyacetone phosphate to glycerol 3-phosphate. Glycerol 3-phosphate is reoxidized by electron transfer to an FAD prosthetic group in a membrane-bound glycerol 3-phosphate dehydrogenase. Subsequent electron transfer to Q to form QH2 allows these electrons to enter the electron-transport chain.

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