Glycolysis in liver

When fructose 2,6-bisphosphate binds to its allosteric site on PFK-1, it increases that enzyme s affinity for its substrate, fructose 6-phosphate, and reduces its affinity for the allosteric inhibitors ATP and citrate. At the physiological concentrations of its substrates ATP and fructose 6-phosphate and of its other positive and negative effectors (ATP, AMP, citrate), PFK-1 is virtually inactive in the absence of fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate activates PFK-1 and stimulates glycolysis in liver and, at the same time, inhibits FBPase-1, thereby slowing gluconeogenesis. 

Effect of insulin and glucagon on the synthesis of key enzymes of glycolysis in liver. 

Fructose can be metabolized by two routes. In adipose tissue and muscle, hexokinase can phosphorylate fructose to fructose 6-phosphate that then enters glycolysis. In liver, most of the enzyme present is glucokinase not hexokinase and this does not phosphorylate fructose. In this tissue, fructose is metabolized instead by the fructose 1-phosphate pathway. 

Metabolic mutants. Predict the effect of each of the following mutations on the pace of glycolysis in liver cells ... 

Radhakrishnaiah, K., Venkataramana, P., Suresh, A., Sivaramakrishna, B., 1992. Effects of lethal and sublethal concentrations of copper on glycolysis in liver and muscle of the freshwater teleost Labeo rohita (Hamilton). J. Environ. Biol. 13, 63-68. 

This is true of skeletal muscle, particularly the white fibers, where the rate of work output—and therefore the need for ATP formation—may exceed the rate at which oxygen can be taken up and utilized. Glycolysis in erythrocytes, even under aerobic conditions, always terminates in lactate, because the subsequent reactions of pymvate are mitochondrial, and erythrocytes lack mitochondria. Other tissues that normally derive much of their energy from glycolysis and produce lactate include brain, gastrointestinal tract, renal medulla, retina, and skin. The liver, kidneys, and heart usually take up... 

Fructose 2,6-Bisphosphate Plays a Unique Role in the Regulation of Glycolysis Gluconeogenesis in Liver... 

In liver, cAMP activates gluconeogenesis, but in muscle, it activates glycolysis. Let s do liver first, and the muscle answer will just be the opposite. So, we want to activate gluconeogenesis in liver in response to increased phosphorylation (increased levels of cAMP). Phosphorylation of our enzyme (PFK-2) must have an effect that is consistent with the activation of gluconeogenesis. If gluconeogenesis is on and glycolysis is off, the level of fructose 2,6-bisphosphate (an activator of glycolysis) must fall. If fructose 2,6-bisphosphate is to fall, the PFK-2 that synthesizes it must be made inactive. So, in liver, phosphorylation of PFK-2 must inactivate the enzyme. 

At the least, we should more systematically classify those drugs that produce a psychedelic sequence in man and show cross tolerance with LSD with respect to the different receptor systems that apparently rank order these drugs in terms of their potency. Such rank order effects have been noted on molluscan ganglia (35) in the clam heart on excitation of cardiac muscle in liver fluke on glycolysis... 

Feed-forward control is more likely to be focused on a reaction occurring at or near the end of a pathway. Compounds produced early in the pathway act to enhance the activity of the control enzyme and so prevent a back log of accumulated intermediates just before the control point. An example of feed-forward control is the action of glucose-6-phosphate, fructose-1,6-bisphosphate (F-l,6bisP) and phosphoenol pyruvate (PEP), all of which activate the enzyme pyruvate kinase in glycolysis in the liver. 

During anaerobic glycolysis in the muscles and erythrocytes, glucose is converted into lactate, releasing protons in the process (see p. 338). The synthesis of the ketone bodies acetoacetic acid and 3-hydroxybutyric acid in the liver (see p. 312) also releases protons. Normally, the amounts formed are small and of little influence on the proton balance. If acids are formed in large amounts, however (e. g., during starvation or in diabetes mellitus see p. 160), they strain the buffer systems and can lead to a reduction in pH (metabolic acidoses lactacidosis or ketoacidosis). 

Glucose 6-phosphate can then be metabolized by glycolysis in the liver or muscle, or it can be dephosphorylated by the action of glucose 6-phosphatase mainly in the liver and released into the bloodstream for use by other tissues of the body. 

This is a major pathway of fructose entry into glycolysis in the muscles and kidney. In the liver, however, fructose enters by a different pathway. The liver enzyme fructokinase catalyzes the phosphorylation of fructose at C-l rather than C-6 ... 

Glucose 1-Phosphate Can Enter Glycolysis or, in Liver, Replenish Blood Glucose... 

The glucose 6-phosphate formed from glycogen in skeletal muscle can enter glycolysis and serve as an energy source to support muscle contraction. In liver,... 

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