Pentose phosphate pathway regulation

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

Larochelle, M.. Drouin, S.. Robert, F., and Turcotte, B. (2006) Oxidative stress-activated zinc cluster protein StbSp has dual activator/repressor fiinctions required for pentose phosphate pathway regulation and NADPH production. Molecular and Cellular Biology. 26. 6690-6701. 

See also Calvin Cycle, Pentose Phosphate Pathway, Regulation of Photosynthesis... 

Zimmer, H.G. (1992). The oxidative pentose phosphate pathway in the heart regulation, physiolcgical significance and clinical implications. Basic Res. Cardiol. 87, 303-316. 

Figure 6-3. The pentose phosphate pathway. In the oxidative phase of the pentose phosphate pathway, NADP is reduced to NADPH H, with feedback regulation by NADPH at the step catalyzed by glucose 6-phosphate dehydrogenase. In the nonoxidative phase, multiple sugar interconversions catalyzed by three different enzymes occur.

Glucose 6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway, is also regulated by this light-driven reduction mechanism, but in the opposite sense. During the day, when photosynthesis produces plenty of NADPH, this enzyme is not needed for NADPH production. Reduction of a critical disulfide bond by electrons from ferredoxin inactivates the enzyme. 

Summary of the Regulation of Glycolysis and Gluconeogenesis The Pentose Phosphate Pathway... 

The transketolase and transaldolase reactions are reversible and so allow either the conversion of ribose 5-phosphate into glycolytic intermediates when it is not needed for other cellular reactions, or the generation of ribose 5-phosphate from glycolytic intermediates when more is required. The rate of the pentose phosphate pathway is controlled by NADP+ regulation of the first step, catalyzed by glucose 6-phosphate dehydrogenase. 

Later studies established the coenzyme role of thiamin diphosphate in transketolase in the pentose phosphate pathway. More recent studies have shown that thiamin triphosphate acts to regulate a chloride channel in nerve tissue. 

Figure 30.5. Regulation of the Pentose Phosphate Pathway. The dehydrogenation of glucose 6-phosphate is the committed step in the pentose phosphate pathway.

Since the intracellular ratios of NADH/NAD+, NADPH/NADP+, and ATP/ adenylates are carefully regulated by the cell, loss of the reduced nucleotide can be compensated by faster operation of the Krebs cycle. But the cell can only make up for a net loss of all nucleotides by an increase in synthesis. The oxidation of NADPH or NADH results in elevated enzyme activity, and this permits the cell to restore the initial ratio of the nucleotides. With NADPH, its oxidation increases the activity of the pentose phosphate pathway. Such increase also occurs following the oxidation of GSH as shown below. Oxidation of either NADPH or GSH, therefore, may be responsible for the apparent increase in the enzymes found in the pentose phosphate pathway after repeated 03 exposure. 

The key regulatory enzyme of the pentose phosphate pathway is positively regulated by... 

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