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biochem exam III REVISED

Lehninger Principles of Biochemistry

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Montalbo, Parrott 1 1) Glucose is converted to glucose-6-phosphate via hexokinase IV, a.k.a. glucokinase. Hexokinase is commited only to the forward reaction to G6P because the reaction has a large –Δ’°G and the byproduct is CO2, which flies away as a gas making it difficult to obtain in the reverse reaction. During gluconeogenisis in the liver, eleven enzymes are used to produce glucose from various beginning substrates. In the last step however, G6P is converted to glucose via hydrolysis by glucose-6-phosphotase. This is carried out in the lumen of the endoplasmic reticulum, and is then shuttled out through glucose transporters into the cytosol, and then eventually to the blood. This is important when blood-sugar levels are low, and the glucose can be used for energy by organs such as the heart. Therefor, it is true that the reverse reaction by hexokinase is irreversible; however the conversion of G6P to glucose is possible by glucose-6-phosphotase. 2) LDH is an isoenzyme that is produced in five different forms. The different isoenzymes play different roles depending on i) different metabolic patterns in different organs, ii) different locations and metabolic roles for the isoenzyme in the same cell, iii) different stages of development in embryonic and in adult tissues, and iv) different responses of isoenzymes to allosteric modulators. LDH1 and LDH2 are found in heart and blood cells. LDH4 and LDH5 are found in the liver. LDH1 is primarily found in the heart and favors rapid oxidation of lactate to pyruvate in the heart; NAD+ and pyruvate strongly inhibit the reaction of pyruvate to lactate in the heart. In the oxygen-rich organ of the heart, LDH is required to catalyze the reverse reaction (explaining Δ’°G=0) so that lactate from the tissues can fuel the heart. In erythrocytes, LDH enables the continuous conversion of glucose to two molecules of excreted lactic acid and ATp (energy) in the anaerobic cells. The final oxidation of NADH+ to NAD in the pyruvate to lactate reaction regenerates the NAD+ that is consumed in the G3P dehydrogenase step earlier in glycolysis. The lactic acid that is excreted is circulated back to the heart for further oxidation. The energy released in red blood cells is not as high as say, in skeletal muscles that are aerobic. In muscle cells when oxygen becomes scarce, there is a high concentration of NADH. This shifts the equilibrium of LDH toward the oxidation of NADH to production of lactate and NAD. This results in energy being released for muscle contraction. The situation os different in heart cells with a high NAD-NADH ratio in which LDH1 oxidizes lactate to pyruvate to generate energy. Under normal conditions, NAD molecules are bound to LDH1 and the reaction equilibrium is shifted toward the production of pyruvate and NADH. Energy is generated further by NADH
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Montalbo, Parrott 2 oxidation. This process reflects the metabolic requirements of different tissue at each differentiation step.
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biochem exam III REVISED - Montalbo Parrott 9 1 Glucose is...

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