Phosphate transport coenzymes

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

Figure 7-4. The electron transport chain. Electrons enter from NADH to complex I or succinate dehydrogenase, which is complex II. Electrons derived from glycolysis through the glycerol-3-phosphate shuttle, complex I, and complex II join at coenzyme Q and are transferred to oxygen as shown. As electrons pass through complexes I, III, and IV, protons are transported across the membrane, creating a pH gradient.

The FADH2 enters the electron-transport chain at coenzyme Q, while the dihydroxyacetone phosphate can return to the cytoplasm. Although this shuttle is generally inefficient, in the sense that only two ATP molecules are produced per FADH2 molecule oxidized, compared with three for NADH oxidation, it provides a mechanism for regeneration of NAD+ in the cytosol. The presence of cytosolic NAD+ is essential for continued glycolysis (see Fig. 11-20). 

As shown in Table 7.1, the total riboflavin concentration in plasma is very much lower than in most tissues. About 50% of plasma riboflavin is free riboflavin, which is the main transport form, with 44% as FAD and the remainder as riboflavin phosphate. The vitamin is largely protein bound in plasma free riboflavin binds to both albumin and a- and /3-globulins, and both riboflavin and the coenzymes also bind to immunoglobulins. The products of photolysis of riboflavin bind to albumin with considerably higher affinity than riboflavin itself this albumin binding may represent a mechanism to prevent tissue... 

In general, NAD+ is involved as an electron acceptor in energy-yielding metabolisni, and the resultant NADH is oxidized by the mitochondrial electron transport chain. The major coenzyme for reductive synthetic reactions is NADPH. An exception here is the pentose phosphate pathway (see Figure 6.4), which reduces NADP+ to NADPH and is the source of about half the reductant for lipogenesis. 

Fig. 5. Proposed mechanism of ATP synthesis coupled to methyl-coenzyme M (CH3-S-C0M) reduction to CH4 The reduction of the heterodisulfide (CoM-S-S-HTP) as a site for primary translocation. ATP is synthesized via membrane-bound -translocating ATP synthase. CoM-S-S-HTP, heterodisulfide of coenzyme M (H-S-CoM) and 7-mercaptoheptanoylthreonine phosphate (H-S-HTP) numbers in circles, membrane-associated enzymes (1) CH3-S-C0M reductase (2) dehydrogenase (3) heterodisulfide reductase 2[H] can be either H2, reduced coenzymeF420 F420H2) or carbon monoxide the hatched box indicates an electron transport chain catalyzing primary translocation the stoichiometry of translocation (2H /2e , determined in everted vesicles) was taken from ref. [117] z is the unknown If /ATP stoichiometry A/iH, transmembrane electrochemical...

Hypervitaminosis Riboflavin. The combination of regulated active transport and conversion to the coenzyme forms prevents hypervitaminosis problems with this vitamin. Toxicities from the water-soluble riboflavin phosphate have not been reported. There are... 

Uptake and Metabolism. The vitamin Bg family consists of pyridoxine, pyridoxal, pyridoxamine, pyridoxine phosphate, pyridoxal phosphate (PLP), and pyridoxamine phosphate (Fig. 8.33). The commercial form is pyridoxine. Pyridoxal phosphate is the coenzyme form. It and pyridoxamine phosphate are from animal tissues. Pyridoxine is from plant tissues. All phosphorylated forms are hydrolyzed in the intestinal tract by phosphatases before being absorbed passively. Conversion to the phosphorylated forms occurs in the liver. Notice that niacin (NAD) and riboflavin (FMN, FAD) are required for interconversion among the vitamin Bq family. The phosphorylated forms are transported to the cells where needed. The major excretory product is 4-pyr-idoxic acid. 

Electron shuttles Enzymatic processes whereby electrons from NADH can be transferred across the mitochondrial barrier. The glycerol 3-phosphate shuttle uses the reduction of dihydroxyacetone phosphate to glycerol 3-phosphate and reoxidation to transfer electrons from cytosolic NADH to coenzyme Q in the electron transport chain. The malate-aspartate shuttle uses malate and aspartate in a two-member transfer exchange to transfer electrons from cytosolic NADH to mitochondrial NADH (see Figures 27-2 and 27-3). 

It is found that the enzyme concerned is a dehydrogenase, and that for oxidation to proceed the coenzyme NAD is required. We have in this oxidation, then, the first example of the dehydrogenase reactions that we discussed in the previous chapter. To add complexity to the picture it was found that the enzyme is multimeric. It contains a suiphydryl group and in fact has three molecules of NAD bound to it - the enzyme also has a requirement for A DP and inorganic phosphate and during the series of reactions ATP is formed directly. This process is called-substrate level phosphorylation to distinguish it from ATP synthesis coupled to the electron transport chain, which is oxidative phosphorylation. 

Many alcoholics such as Al Martini develop thiamine deficiency because alcohol inhibits the transport of thiamine through the intestinal mucosal cells. In the body, thiamine is converted to thiamine pyrophosphate (TPP). TPP acts as a coenzyme in the decarboxylation of a-keto acids such as pyruvate and a-ketoglutarate (see Fig. 8.11) and in the utilization of pentose phosphates in the pentose phosphate pathway. As a result of thiamine deficiency, the oxidation of a-keto acids is impaired. Dysfunction occurs in the central and peripheral nervous system, the cardiovascular system, and other organs. 

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