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Phosphorylation of glucose commits it to metabolism CH2OH within the cell because glucose-6-P cannot be transported back across the plasma O membrane buy 50 mg pristiq with mastercard. The phosphorylation reaction is irreversible under physiologic condi- H H 0 tions because the reaction has a high negative G pristiq 100 mg lowest price. Phosphorylation does not, HO OH H OH however, commit glucose to glycolysis. Glucose-6-P is a branchpoint in carbohydrate metabolism. It is a precursor for H OH almost every pathway that uses glucose, including glycolysis, the pentose phosphate Glucose pathway, and glycogen synthesis. From the opposite point of view, it also can be ATP generated from other pathways of carbohydrate metabolism, such as glycogenoly- hexokinase sis (breakdown of glycogen), the pentose phosphate pathway, and gluconeogenesis glucokinase (liver) ADP (the synthesis of glucose from non-carbohydrate sources). Hexokinases, the enzymes that catalyze the phosphorylation of glucose, are a 2– CH2OPO3 family of tissue-specific isoenzymes that differ in their kinetic properties. The O isoenzyme found in liver and cells of the pancreas has a much higher Km than H H other hexokinases and is called glucokinase. In many cells, some of the hexokinase HO OH H OH is bound to porins in the outer mitochondrial membrane (voltage-dependent anion channels; see Chapter 21), which gives these enzymes first access to newly synthe- H OH sized ATP as it exits the mitochondria. CONVERSION OF GLUCOSE-6-P TO THE TRIOSE PHOSPHATES Other Glycolysis Pentose Glycogen In the remainder of the preparative phase of glycolysis, glucose-6-P is isomerized pathways phosphate synthesis to fructose 6-phosphate (fructose-6-P), again phosphorylated, and subsequently pathway cleaved into two 3-carbon fragments (Fig 22. The next step of glycolysis, phosphorylation of fructose-6-P to fructose 1,6- Hexokinases, other kinases, and bisphosphate (fructose-1,6-bisP) by phosphofructokinase-1 (PFK-1), is generally many other enzymes that catalyze considered the first committed step of the pathway. This phosphorylation requires reactions involving the hydrolysis 2 2 ATP and is thermodynamically and kinetically irreversible. The Mg forms a com- ocably commits glucose to the glycolytic pathway. PFK-1 is a regulated enzyme in plex with the phosphate groups of ATP. Fructose-1,6-bisP is cleaved into two phosphorylated 3-carbon compounds (triose phosphates) by aldolase (see Fig. Dihydroxyacetone phosphate (DHAP) is isomerized to glyceraldehyde 3-phosphate (glyceraldehyde-3-P), which is a triose phosphate. Thus, for every mole of glucose entering glycolysis, 2 moles of glyceraldehyde-3-P continue through the pathway.
Alanine All cells are continuously supplied with glucose under normal circumstances order 50mg pristiq with amex; the body maintains a relatively narrow range of glucose concentration in the blood Pyruvate Lactate (approximately 80-100 mg/dL) in spite of the changes in dietary supply and tissue demand as we sleep and exercise cheap 100 mg pristiq with visa. Low blood glucose levels (hypoglycemia) are prevented by a release of glucose from the OAA large glycogen stores in the liver (glycogenolysis); by synthesis of glucose from lac- TCA tate, glycerol, and amino acids in liver (gluconeogenesis) (Fig. Production of blood glucose from glycemia) are prevented both by the conversion of glucose to glycogen and by its glycogen (by glycogenolysis) and from ala- conversion to triacylglycerols in liver and adipose tissue. Thus, the pathways for nine, lactate, and glycerol (by gluconeogene- glucose utilization as a fuel cannot be considered as totally separate from pathways sis). PEP phosphoenolpyruvate; OAA involving amino acid and fatty acid metabolism (Fig. Overview of the major pathways of glucose metabolism. Pathways for production of blood glucose are shown by dashed lines. FA fatty acids; TG triacylglycerols; OAA oxaloacetate; PEP phosphoenolpyruvate; UDP-G UDP-glucose; DHAP dihydroxyacetone phosphate. Intertissue balance in the utilization and storage of glucose during fasting and feeding is accomplished principally by the actions of the hormones of metabolic homeostasis—insulin and glucagon (Fig. However, cortisol, epinephrine, nor- epinephrine, and other hormones are also involved in intertissue adjustments of supply and demand in response to changes of physiologic state. Glucagon release Blood glucose Insulin release Glycogenolysis Glycogen synthesis Gluconeogenesis Fatty acid synthesis Lipolysis Triglyceride synthesis Liver glycolysis Liver glycolysis Fig 10. Pathways regulated by the release of glucagon (in response to a lowering of blood glucose levels) and insulin (released in response to an elevation of blood glucose levels). Tissue-specific differences occur in the response to these hormones, as detailed in the subse- quent chapters of this section.