Carbohydrate metabolism mechanisms

One of the steps in the biological pathway for carbohydrate metabolism is the conversion of fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Propose a mechanism for the transformation. 

Ghanges in the availability of substrates are responsible for most changes in metabolism either directly or indirectly acting via changes in hormone secretion. Three mechanisms are responsible for regulating the activity of enzymes in carbohydrate metabolism (1) changes in the rate of enzyme synthesis, (2) covalent modification by reversible phosphorylation, and (3) allosteric effects. 

In all organisms, carbohydrate metabolism is subject to complex regulatory mechanisms involving hormones, metabolites, and coenzymes. The scheme shown here (still a simplified one) applies to the liver, which has central functions in carbohydrate metabolism (see p. 306). Some of the control mechanisms shown here are not effective in other tissues. 

DBCP is a genotoxic in microbial and mammalian assays. The mechanism for DBCP-induced testicular toxicity may be related to direct DNA damage. Binding of DBCP metabolites to testicular cell DNA has been demonstrated. Alternatively, inhibition of sperm carbohydrate metabolism could also account for DBCP toxicity to epididymal sperm. 

T. M. Gloster, J. P. Turkenburg, J. R. Potts, B. Henrissat, and G. J. Davies, Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora, Chem. Biol., 15 (2008) 1058-1067. 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. Therapeutic Effect Necessary for cell growth and replication, hematopoiesis, and myelin synthesis. Pharmacokinetics In the presence of calcium, absorbed systemically in lower half of ileum. Initially, bound to intrinsicfactor this complex passes down intestine, binding to receptor sites on ileal mucosa. Protein binding High, Metabolized in the liver. Primarily eliminated unchanged in urine. Half-life 6 days. 

Mechanism of Action A synthetic nitrofuran that inhibits bacterial enzymes involved in carbohydrate metabolism. Therapeutic Effect Inhibits a variety of enzymes. Bactericidal. 

Transglycosylation. An enzymatic process, transglycosylation, plays an important role in carbohydrate metabolism. Figure 6 represents the formation of the disaccharide, sucrose, as an example of this mechanism. In the upper reaction of Fig. 6, glucose-1-phosphate is the glycosyl donor and... 

A reversible covalent modification that plants use extensively is the reduction of cystine disulfide bridges to sulf-hydryls. Many of the enzymes of photosynthetic carbohydrate synthesis are activated in this way (table 9.3). Some of the enzymes of carbohydrate breakdown are inactivated by the same mechanism. The reductant is a small protein called thioredoxin, which undergoes a complementary oxidation of cysteine residues to cystine (fig. 9.5). Thioredoxin itself is reduced by electron-transfer reactions driven by sunlight, which serves as a signal to switch carbohydrate metabolism from carbohydrate breakdown to synthesis. In one of the regulated enzymes, phosphoribulokinase, one of the freed cysteines probably forms part of the catalytic active site. In nicotinamide-adenine dinucleotide phosphate (NADP)-malate dehydrogenase and fructose-1,6-bis-... 

Biochemistry resulted from the early elucidation of the pathway of enzymatic conversion of glucose to ethanol by yeasts and its relation to carbohydrate metabolism in animals. The word enzyme means "in yeast," and the earlier word ferment has an obvious connection. Partly because of the importance of wine and related products and partly because yeasts are relatively easily studied, yeasts and fermentation were important in early scientific development and still figure widely in studies of biochemical mechanisms, genetic control, cell characteristics, etc. Fermentation yeast was the first eukaryote to have its genome elucidated. 

Thus it seems certain that glucuronide formation is closely related to carbohydrate metabolism, but the details of the mechanism are, as yet, unknown. The important points which have to be elucidated refer to the immediate precursor or precursors of D-glucuronic acid and to the nature of the conjugation process, for example, whether D-glucuronic acid is built up on the aglycon molecule or whether direct union of the acid with the aglycon can occur. 

Mechanism and susceptibility factors Biguanides in high doses inhibit the oxidation of carbohydrate substrates by affecting mitochondrial function. Anoxidative carbohydrate metabolism stimulates the production of lactate. High lactate production leads to lactic acidosis (type B) with a low pH (<6.95). Hyperlactatemia was common in patients taking buformin, even without alcoholism or impaired liver, kidney, or cardiac function (70). 

Milman, L.S. and Yurovitsky, Yu.G. (1973). Mechanisms of Enzymatic Regulation of Carbohydrate Metabolism at Early Embryogenesis (In Russian). Nauka, Moscow, 235 pp. 

In addition to being incorporated into tissue proteins, amino acids, after losing their nitrogen atoms by deamination and/or transamination, may be catabolized to yield energy or to form glucose. Conversely, the nonessential amino acids may be synthesized from carbohydrate metabolism intermediates and ammonia or from essential amino acids. This section is devoted to the mechanisms of such metabolic processes and their interrelationships with carbohydrate and lipid metabolic pathways. 

Although hematological, biochemical, hepatic, and renal parameters are not specific for DNOC exposure, these parameters may be measured to determine disease states caused by DNOC. One animal study demonstrated changes in these parameters following oral exposure to DNOC for intermediate-duration (Den Tonkelaar et al. 1983). Based on DNOC s mechanism (uncoupling of exudative phosphorylation), urinary ketone levels and urine and blood glucose levels may be monitored for effects on carbohydrate metabolism. 

As noted previously, like skeletal muscle, glycogen depletion in liver during endurance exercise is much less in trained animals and in animals who have had free fatty acids artificially elevated. No evidence exists that the mechanism proposed by Randle to account for the inhibition of carbohydrate metabolism in muscle by oxidation of fatty acids is operative in the liver. Thus other factors must be responsible for the slower rate of liver glycogen depletion in these situations. Such factors may include a smaller increase in catecholamine levels, a smaller reduction in insulin levels, and a smaller reduction in blood flow to the liver during exercise (19,20). 

Regulation of Pyruvate Dehydrogenase Activity Pyruvate dehydrogenase is the key enzyme that commits pyruvate (and hence the products of carbohydrate metabolism) to complete oxidation (via the tricarboxyUc acid cycle) or lipogenesis. It is subject to regulation by both product inhibition and a phosphorylation/dephosphorylation mechanism. Acetyl CoA and NADH are both inhibitors, competing with coenzyme A and NAD+. 

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