«First steps of glycolysis
The first enzyme used in the second phase of glycolysis is the glyceraldehyde 3-phosphate dehydrogenase; dehydrogenases are enzymes that catalyze the transfer of reducing power from a reducing molecule that oxidizes to another molecule that is reduced (redox reaction). The substrates of this enzyme are NAD (nicotidamide adenine dinucleotide) and FAD (flavin adenin dinucleotide ).
In this step the dehydrogenase catalyzes the conversion of glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate: on the same catalytic site, the aldehyde group is oxidized to carboxyl with consequent reduction of NAD + to NADH and, subsequently, the carboxyl group is able to form an anhydride bond with an orthophosphate. The first process is very exergonic (it releases energy) while the second is very exergonic (it requires energy); if there were no catalytic site, the global reaction would not take place: the first reaction would occur with the release of energy which would be dispersed as heat and which, therefore, would not be usable to form the anhydride bond.
After the formation of 1,3-bisphosphoglycerate, the enzyme resumes its starting structure and is ready to act on a new substrate.
Then comes the phosphoglycerate kinase which allows the transfer of a phosphoryl from 1,3-bisphosphoglycerate to an ADP molecule; we have obtained ATP (one ATP for each molecule of glyceraldehyde 3-phosphate, therefore, two ATPs for each initial glucose molecule) which compensates the energy expenditure of the first phase of glycolysis.
The arsenate anion (AsO43-) affects the glycolytic pathway as it can replace the phosphate in the first reaction of the second phase of glycolysis, giving 1-arsenio 3-phosphoglycerate which is highly unstable and, as soon as it is free from the catalytic site, hydrolyzes releasing the "arsenate returning to the circulation. Therefore, the arsenate mimics the action of the phosphate and enters the catalytic site: in the presence of the arsenate, the reaction that produces ATP (from 1,3-bisphosphoglycerate to 3-phosphoglycerate) does not take place because the 3-phosphate glyceraldehyde is converted directly to 3-phosphoglycerate; with no ATP available, cells die (arsenic acid poisoning).
In the third reaction of the oxidative phase, 3-phosphoglycerate is converted into 2-phosphoglycerate by the action of phosphoglycerate mutase; the reaction involves a 2,3-bisphosphoglycerate intermediate.
In the next step, an enzyme intervenes enolase which is able to catalyze the elimination of a water molecule from the carbonaceous skeleton of 2-phosphoglycerate obtaining the phosphoenol pyrivate (PEP);
PEP has a high potential for transferring a phosphoryl: it transfers, through the action of an enzyme pyruvate kinase, a phosphoryl to an ADP to give ATP, in the fifth step of the second phase, obtaining pyruvate.
2-phosphoglycerate and 3-phosphoglycerate have a low transfer power of a phosphoryl therefore, to obtain ATP from these molecules, 3-phosphoglycerate is converted into 2-phosphoglycerate, during glycolysis, because it is obtained from the latter. the PEP which is a species with a high transfer potential.
Before continuing, let's open a parenthesis on 2,3-bisphosphoglycerate; the latter is present in all cells in which glycolysis occurs in a very low concentration (it is the intermediate of the third reaction of the second phase of glycolysis). In erythrocytes, on the other hand, 2,3-bisphosphoglycerate has a stationary concentration of 4-5 mM (maximum concentration) because they possess an enzymatic patrimony which has the task of producing it; in erythrocytes there is a deviation from glycolysis to produce 2,3-bisphosphoglycerate: 1,3-bisphosphoglycerate is converted into 2,3-bisphosphoglycerate by the action of bisphosphoglycerate mutase (erythrocyte) and 2,3-bisphosphoglycerate, by the action of bisphosphoglycerate phosphatase (erythrocyte) becomes 3-phosphoglycerate. Then, in the erythrocytes, a part of the 1,3-bisphosphoglycerate obtained from glycolysis is converted into 2,3-bisphosphoglycerate which then returns to the glycolytic pathway as 3-phosphoglycerate; in doing so, the third step of the oxidative phase of the glycolysis from which ATP is obtained. The amount of ATP lost is the price that an erythrocyte is willing to pay to keep the concentration of 2,3-bisphosphoglycerate that these cells need because it affects the ability of "hemoglobin to bind" oxygen.
We have seen that in the first reaction of the second phase of glycolysis the NAD + is reduced to NADH but it is necessary that, after obtaining the pyruvate, the NADH is reconverted to NAD +: this occurs with lactic fermentation (lactate is obtained) or by alcoholic fermentation (pyruvate decarboxylase which decarboxylates pyruvate and a dehydrogenase which forms ethanol come into play); fermentations do not involve oxygen (anaerobes).
Due to lactic fermentation, lactic acid, if not adequately disposed of, accumulates in the muscles and, releasing H +, causes involuntary muscle contraction and, therefore, cramps; a muscle in strong stress can also reach a minimum pH of 6.8 .
Through the Cori cycle, part of a muscle's fatigue is transferred to the liver when the muscle is overloaded. Suppose that the muscle works without oxygen supply (wrong assumption): if the muscle works moderately, the ATP needed for contraction is provided exclusively by glycolysis. If the activity of the muscle increases and additional ATP is required, speed up the aerobic metabolism, converting lactate, which is thus disposed of, into glucose. In reality, the muscle exploits the aerobic metabolism: if there is availability of oxygen, the muscle exploits, above all, the ATP provided by the aerobic metabolism and, when there is no more oxygen available, the anaerobic metabolism is accelerated through the Cori cycle. This cycle assumes that lactate is transferred from the muscle to the liver, where, by expending energy, more glucose is produced which returns to the muscle. Through this cycle, part of the ATP consumed in the muscle is supplied by the liver which, through the gluconeogenesis process, is capable of producing glucose which can be used by the muscle to obtain ATP.
The glucose metabolism described up to now does not include oxygen but the aerobic metabolism of glucose allows to obtain 17-18 times higher quantities of ATP than that obtained with the glycolytic pathway, therefore, when the cell has the possibility to choose between aerobic and ed anaerobe, favors the former.
In aerobic metabolism, pyruvate enters the mitochondria where it undergoes transformations and eventually carbon dioxide and water are obtained; in this way 34 molecules of ATP are obtained for each molecule of degraded glucose.
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