Describe How Anaerobic Glycolysis Leads To The Net Production Of Protons In The Cytoplasm Of The Cell
...aldehyde-3-P and thus two molecules of NADH and 2H+ are generated for every one molecule of glucose. Coenzyme NAD+ is the hydrogen acceptor in the glyceraldehyde-3-P dehydrogenase reaction. There is an enzyme controlled transfer of a hydride ion (:H-) from the aldehyde group of the glyceraldehyde-3-P to the nicotinimide ring of NAD+. This produces the reduced coenzyme NADH. The other hydrogen atom from the glyceraldehyde-3-P is released in solution as H+. This is not, however, where the net production of protons is, as these protons are quickly used to produce NAD+ as will be explained later. Phosphoglycerate kinase catalyses the next step which is the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate with the production of one molecule of ATP from ADP. Because these are three carbon compounds there are two molecules of ATP produced for each molecule of glucose that enters the pathway. Phosphoglycerate mutase catalyses the 8th step which is the conversion of 3-phosphoglycerate to 2-phosphoglycerate which is essentially just a shift of the phosphate group from the OH on C3 to the OH on C2. The penultimate reaction is catalysed by enolase as phosphoenolpyruvate and water are formed from 2-phosphoglycerate. In the final reaction of glycolysis pyruvate kinase catalyses the formation of pyruvate from phosphoenolpyruvate with the formation of one molecule of ATP from ADP. This reaction is spontaneous and is another control point in glycolysis. Control points in glycolysis are irreversible reactions which are operating far from equilibrium. These are the reactions catalysed by hexokinase, phosphofructokinase, and pyruvate kinase. PFK, an allosteric enzyme, is the main control point as it is the first committed step – it commits glucose to glycolysis – before this step fructose-6-phosphate can be converted back to glucose or to glycogen for storage. PFK is inhibited by ATP as ATP lowers the affinity of PFK for fructose-6-phosphate by binding to a regulatory site on the enzyme. PFK is also inhibited by citrate but the inhibition is reversed by AMP and H+. In the liver PFK would not normally be able to function due to the high ATP concentration but there is a specific activator of PFK, fructose-2,6-bisphosphate which allows PFK to function in high ATP concentrations. It increases the affinity of PFK for fructose-6-phosphate and reduces the inhibitory effect of ATP. Fructose-2,6-bisphosphate is produced from fructose-6-phosphate by a special bifunctional enzyme, fructose-6-phosphate:2-kinase-fructose-2,6-bisphosphatase. It has two active sites so it can act as a phosphatase or a kinase. The production of fructose-2,6-bisphosphate from fructose-6-phosphate requires one molecule of ATP. The phosphatase activity occurs when the enzyme is phosphorylated and the kinase activity occurs when the dephosphorylated enzyme is produced. It is phosphorylated in response to glucagon – the signal of fasting – when glucose needs to be conserved such that fructose-2,6-bisphosphatase is not produced and so PFK is inhibited by the high ATP concentration and thus glycolysis is inhibited. Hexokinase is inhibited by the product of the reaction, glucose-6-phosphate and if PFK activity falls, fructose-6-phosphate will build up and thus so will glucose-6-phosphate and so hexokinase will be inhibited and so will conversion of glucose. This will again happen in response to glucagon so that the glucose going through glycolysis is reduced. Pyruvate kinase controls the outflow to pyruvate of phosphoenolpyruvate and one molecule of ATP is generated. Pyruvate kinase is activated by fructose-1,6-bisphosphate and inhibited by ATP and alanine. So the ‘balance sheet’ for glycolysis is as follows: 2 ATP ~P bonds are expended and 4 ~P bonds of ATP are produced (2 from each of two 3C fragments from glucose). Thus, there is a net production of 2 ~P bonds of ATP per molecule of glucose. The overall process of anaerobic glycolysis is shown below: Glucose + 2ADP + 2Pi 2lactate + 2ATP + 2H2O + 2H+ In anaerobic glycolysis there are two fates for the pyruvate produced. The first route is the production of ethanol and CO2 in alcohol fermentation as exhibited by some plants and micro-organisms. The second route is the reduction to lactate via lactic acid fermentation. This occurs for example in vigorously contracting skeletal muscle when there is not enough oxygen for aerobic respiration. Lactate is produced from pyruvate as follows: Glucose Pyruvate Lactate Lactate is the obligatory reduced product of anaerobic glycolysis. Its production is necessary so that NADH + and H+ can be oxidised back to NAD+ so that glycolysis can continue. The reduction of pyruvate to lactate is catalysed by lactate dehydrogenase which forms the L-isomer of lactic acid (lactate at pH 7). The overall equilibrium strongly favours lactate formation. Because the overall proce...