Enzymes glucose-6-phosphatase

The reverse of this reaction does occur in some cells (e.g. hepatocytes), catalysed by the enzyme glucose-6-phosphatase, but the direction is always towards glucose formation, i.e. glucose 6-phosphate is never produced by this reaction in vivo. The question is, why not ... 

The conversion of glucose 6-phosphate to glucose occurs in a reaction catalysed by the enzyme glucose-6-phosphatase ... 

The enzyme glucose 6-phosphatase, which catalyses the hydrolysis of glucose 6-phosphate to form glucose, is also present in the liver cell. 

Transporters in the plasma membrane of hepatocytes allow insulin-independent transport of glucose and other sugars in both directions. In contrast to muscle, the liver possesses the enzyme glucose-6-phosphatase, which can release glucose from glucose-6-phosphate. 

Isoproterenol is the most potent stimulant of skeletal muscle glycogenolysis, followed by epinephrine and norepinephrine. (3z-Adrenoceptors mediate muscle glycogenolysis. Stimulation of skeletal muscle glycogenolysis will raise blood lactic acid levels rather than blood glucose levels because skeletal muscle lacks the enzyme glucose-6-phosphatase, which catalyzes the conversion of glucose-6-phosphate to glucose. 

Heavy metals stimulate or inhibit a wide variety of enzyme systems (16, 71, 72), sometimes for protracted periods (71, 73). These effects may be so sensitive as to precede overt toxicity as in the case of lead-induced inhibition of 8 ALA dehydrase activity with consequential interference of heme and porphyrin synthesis (15, 16). Urinary excretion of 8 ALA is also a sensitive indicator of lead absorption (74). Another erythrocytic enzyme, glucose-6-phosphatase, when present in abnormally low amounts, may increase susceptibility to lead intoxication (75), and for this reason, screens to detect such affected persons in lead-related injuries have been suggested (76). Biochemical bases for trace element toxicity have been described for the heavy metals (16), selenium (77), fluoride (78), and cobalt (79). Heavy metal metabolic injury, in addition to producing primary toxicity, can adversely alter drug detoxification mechanisms (80, 81), with possible secondary consequences for that portion of the population on medication. 

The main site of gluconeogenesis is the liver, although it also occurs to a far lesser extent in the kidneys. Very little gluconeogenesis occurs in brain or muscle. Within liver cells, the first enzyme of gluconeogenesis, pyruvate carboxylase, is located in the mitochondrial matrix. The last enzyme, glucose 6-phosphatase is bound to the smooth endoplasmic reticulum. The other enzymes of the pathway are located in the cytosol. 

The fate of the glucose 6-phosphate depends on the tissue. Liver contains the enzyme glucose 6-phosphatase which converts the glucose 6-phosphate to glucose, which then diffuses out into the bloodstream and so maintains the blood glucose concentration ... 

Describe a possible means for the cytochemical detection and localization of the enzyme glucose 6-phosphatase it exists in liver and catalyzes the following reaction ... 

Figure 2.5 Gluconeogenesis is the reversal of glycolysis, attained through the use of four unique enzymes glucose-6-phosphatase (A), fructose-1,6-bisphosphatase (5), PEP carboxykinase (6) and pyruvate carboxylase (7). Although phosphoglycerate kinase is shared with glycolysis, in gluconeogenesis this reaction requires the input of ATP.

The answer is d. (Murray, pp 505-626. Scriver, pp 4029-4240. Sack, pp 121-138. Wilson, pp 287-320.) Although the liver is the major site of the formation of free glucose to maintain blood glucose levels, the kidneys and intestinal epithelium (e.g., duodenum, jejunum, and ileum) may also release glucose. All of these tissues contain the enzyme glucose-6-phosphatase, an endoplasmic reticulum enzyme that dephosphorylates glucose and allows it to be transferred out of the cells. No other tissues in mammals contain this enzyme. 

The third bypass reaction requires the hydrolysis of glucose-6-P04 to glucose, which then can leave the liver and enter the blood for distribution to other tissues. This reaction requires a third new enzyme, glucose-6-phosphatase ... 

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