The Fate of Glucose-6-phosphate

Assuming that the stores are some 300 g after a night s fast, the glycogen build up is shown in Fig. 6.13b for different values of the half-time. The fastest (6 h) corresponds to a build up of 350 g in 6 h (0.97 g mim1) or some 14 mg kg mim1 for a person of 70 kg. With the fast storage rate, the glycogen stores are filled rapidly, 

Insufficient removal of G6P, leading to a high intracellular free glucose. This blocks the muscle uptake, but as the whole-body uptake continues, at least in healthy people, it requires a yet unknown and precisely timed signal from the muscle to other organs. 

Activation of the glycolysis with lactate formation and/or lipogenesis, as shown in Fig. 6.7b. 

It is reasonable to assume option 2, but option 1 may be possible in patients witb type 2 diabetes, where glycogen synthesis appears to be decreased more than uptake and phosphorylation [94, 95]. 

The first choice is lactate formation. The lactate concentration is typically increased by a factor of two or three during high glucose uptake [90]. Lactate is not only an escape route for surplus glucose uptake, but as most cells can take up lactate, it can then be oxidized or stored elsewhere. The signal for lactate formation is unknown. A possible candidate is G6P, which increases as the glycogen stores fill up. 

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Glucose 6-phosphate is metabolized by both the glycolytic pathway (Chapter 16) and the pentose phosphate pathway. How is the processing of this important metabolite partitioned between these two metabolic routes The cytoplasmic concentration of NADP+ plays a key role in determining the fate of glucose 6-phosphate. 

Describe the fates of glucose 6-phosphate in cells. Outline the pathways that give rise to glucose 6-phosphate, and discuss the release of glucose into the blood. 

Because the fate of glucose 6-phosphate depends largely on the relative activities of glycogen synthase and phosphofructokinase, to understand the direction of carbon flow from glncose, it is necessary to nnderstand how these enzymes are regulated. 

The fate of glucose 6-phosphate and glucose depends on the nature of the tissue. In skeletal muscle cells, the non-phosphorylated glucose which accounts for about 10% of the cleavage products (branches occur every 8-12 glucose residues) may... 

The hydrolysis of glucose-6-su fate will proceed further to the right (higher and more negative AC) because the product, HSO, is a strong icid (pK,= 1.9) that spontaneously ionizes at pH 7 to SOj -l- H -. The product of glucose-6-phosphate hydrolysis. 

The major fate of glucose 6-phosphate is to enter the pathway of glycolysis, which produces pyruvate and generates NADH and ATP. 

Figure 21.3 Fates of glucose 6-phosphate. Glucose 6-phosphate derived from glycogen can (1) be used as a fuel for anaerobic or aerobic metabolism as in. for instance, muscle (2) be converted into free glucose in the liver and subsequently released into the blood (3) be processed by the pentose phosphate pathway to generate NADPH or ribose n a variety of tissues.

The biosynthesis of glycogen occurs from glucose-6-phosphate. As indicated earlier, this is one of several alternative fates of glucose-6-phosphate in addition to glycolysis. Glucose-6-phosphate via phosphoglucomutase and glucose-1,6-bisphosphate can be reversibly... 

The major fate of glucose 6-phosphate is oxidation via the pathway of glycolysis (see Chapter 22), which provides a source of ATP for all cell types. Cells that lack mitochondria cannot oxidize other fuels. They produce ATP from anaerobic glycolysis (the conversion of glucose to lactic acid). Cells that contain mitochondria... 

This enzyme is called PFK-1 to distinguish it from a second enzyme (PFK-2) that catalyzes the formation of fructose 2,6-bisphosphate from fructose 6-phosphate in a separate pathway. The PFK-1 reaction is essentially irreversible under cellular conditions, and it is the first committed step in the glycolytic pathway glucose 6-phosphate and fructose 6-phosphate have other possible fates, but fructose 1,6-bisphosphate is targeted for glycolysis. 

A liver cell has a high concentration of glucose 6-phosphate, which inhibits the activity of hexokinase. What is the fate of the glucose 6-phosphate ... 

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 ... 

Williams JF, Clark MG, Blackmore PF. The fate of in glucose 6-phosphate synthesised from [1- C. ribose 5-phosphate by enzymes of rat liver. Biochem. J. 1978 176 241-256. 

Tracing glucose. Glucose labeled with at C-6 is added to a solution containing the enzymes and cofactors of the oxidative phase of the pentose phosphate pathway. What is the fate of the radioactive label ... 

The factors governing the flow of molecules in metabolism can be further understood by examining three important molecules glucose 6-phosphate, pyruvate, and acetyl CoA. Each of these molecules has several contrasting fates ... 

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