Why is glycolysis an example of catabolism



Glycolysis (from the Greek glykys = sweet and lysis = dissolve) is the first part of the glucose breakdown (catabolism) in the cells of most living things. In this biochemical breakdown pathway, one molecule of glucose is converted into two pyruvate molecules in ten enzymatically catalyzed reactions.

The very well known and studied form of glycolysis is the Embden-Meyerhof-Weg (after Gustav Embden and Otto Meyerhof). An alternative way is that Entner-Doudoroff way. The term glycolysis can be used to encompass all alternative degradation pathways. However, glycolysis is used here as a synonym for the Embden-Meyerhof-Weg used.

Place of glycolysis

Glycolysis is the most important breakdown pathway for carbohydrates in the metabolism and takes place in the cytoplasm of every cell. In the past it was only understood to mean the breakdown of carbohydrates Oxygen starvation conditions via pyruvate to lactate, we now know that the breakdown of glucose to pyruvate takes place in the same way even when there is sufficient oxygen supply: it takes place in both cases without "consumption" of oxygen (i.e. anaerobically).

In prokaryotes and in predominantly anaerobic cells or tissues (skeletal muscle) of eukaryotes, pyruvate is anaerobically transformed into lactic acid or, as in many yeasts, into ethanol and carbon dioxide (CO2) metabolized.

Aerobic tissues (prototype: heart muscle) break down the "C3 body" pyruvate to acetyl-CoA and carbon dioxide and the acetyl-CoA further in the citric acid cycle to CO2 and hydrogen. The hydrogen is bound to the hydrogen carriers nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD) (NADH and FADH, respectively)2). The energy from the oxidation of hydrogen in the respiratory chain of the mitochondria is used to synthesize ATP (oxidative phosphorylation).

Glycolysis is the only metabolic pathway that practically all modern organisms have in common, indicating that it was very early on; glycolysis may have originated in the first prokaryotes around 3.5 billion years ago.

The reaction steps of glycolysis

The first step in glycolysis is the phosphorylation of glucose to glucose-6-phosphate (G6P). Depending on the cell type, this reaction is catalyzed by the enzyme hexokinase (for example in the brain) or glucokinase (for example in the liver and pancreas). Phosphorylation uses 1 ATP, which is a good investment. The cell membrane is permeable for glucose, but not for the glucose-6-phosphate produced by phosphorylation, which accumulates in the cell and, by shifting the equilibrium on the membrane, favors the uptake of glucose. Glucose-6-phosphate is then converted into fructose-6-phosphate (F6P) by the phosphohexose isomerase. (At this point, fructose can also enter the glycolytic pathway through phosphorylation.)

Then, under the action of the key enzyme of glycolysis, phosphofructokinase, fructose-6-phosphate is phosphorylated with a molecule of ATP to form fructose-1,6-bisphosphate (1,6-FBP), whereby ADP is formed from ATP. The associated transfer of energy is justified in two ways: on the one hand, this step - in addition to glucokinase and pyruvate kinase - also makes glycolysis irreversible, and on the other hand, the second phosphate group allows the glucose ring to be cleaved by aldolase into dihydroxyacetone phosphate (DHAP) (phosphorylated keto-keto -Triose) and glyceraldehyde-3-phosphate (3-GAP) (phosphorylated aldo-triose). Dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate by triosephosphate isomerase (TIM). Each of the two resulting glyceraldehyde-3-phosphate molecules is then exposed to NAD+ and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is oxidized to 1,3-bisphosphoglycerate (1,3-BPG). A thioester is formed in an intermediate stage. In a chemical sense, this reaction causes the oxidation of the carbonyl group to the carboxyl group, i.e. the transition from sugar (phosphate) to carboxylic acid (phosphate).

In the next step, the phosphoglycerate kinase generates one molecule of ATP when converting 1,3-bisphosphoglycerate to 3-phosphoglycerate by transferring a phosphate residue to ADP. This balances the energy balance of the previous glycolysis: two molecules of ATP were used and two were recovered. This ATP synthesis needs ADP as a basis. If the cell already has a lot of ATP (and thus little ADP), the reaction continues at this point until enough ADP is available again. This feedback regulation is important because ATP breaks down relatively quickly when it is not used. This prevents overproduction of ATP. Phosphoglyceromutase then catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate, which eventually becomes phosphoenolpyruvate with the help of enolase. This is finally converted into pyruvate (= anion of pyruvic acid) in the pyruvate kinase reaction with the generation of another ATP. This step is also regulated by ADP.

Course of the reaction of glycolysis

Energetic aspects of glycolysis

Equilibrium position

It is noteworthy that most of the reactions that follow the formation of fructose-1,6-bisphosphate are energetically unfavorable. They would hardly take place if they were not caused by the energetically favorable kinase reactions (phosphofructokinase (PFK), Phosphoglycerate kinase (PGK), Pyruvate kinase (PK)) Would be "pulled through". The underlying strategy is worth mentioning, as this equilibrium situation favors the Gluconeogenesis, that is the synthesis of glucose from pyruvate with a favorable energy status. This requires all enzymes, with the exception of two of the “draft horses” mentioned, which are solely assigned to glycolysis and here are strongly exergonic with -14 and -24 kJ / mol.

Energy yield under anaerobic and aerobic conditions

Glycolysis delivers 2 molecules of ATP per molecule of glucose when it is complete. Aerobic prokaryotes and the mitochondria of eukaryotes can aerobically obtain a maximum of 34 more molecules of ATP from the two simultaneously formed pyruvate molecules (i.e. a total of 36 molecules of ATP); In eukaryotes, this balance depends on the path in which NADH + H is formed in the cytosol+ passes through the mitochondrial membrane (shuttle systems). However, complete glycolysis can also take place in the presence of oxygen. This is the case, for example, with some tumor cells, but also with erythrocytes, which lack the mitochondria for the respiratory chain.

The glycolysis reactions up to pyruvate are carried out under both aerobic and anaerobic conditions. The regeneration of the oxidizing agent (coenzyme) NAD+, which is used for the oxidation of glyceraldehyde-3-phosphate by the assigned dehydrogenase GAPDH and thereby to NADH + H+ takes place in the first case in the respiratory chain. In the case of anaerobic metabolism, the strongly exergonic (ΔGO´ = –25 kJ / mol) Lactate dehydrogenase (LDH) reaction responsible: reduction of pyruvate with NADH + H+ supplies lactate and regenerates NAD+ (In the case of yeasts that produce ethanol, this function is performed by two enzymes, pyruvate decarboxylase plus alcohol dehydrogenase). This "circular process" is the content of the following figure:

 

Mutual dependence of the GAPDH and LDH reactions in anaerobic glycolysis. With the exception of small amounts of NADH, H+, which are converted by glycerol phosphate dehydrogenase (GDH), the bulk of NAD+ can be regenerated by the LDH reaction.

Inhibitors

Iodine acetate inhibits glyceral-3-phosphate dehydrogenase, which makes glyceral-3-phosphate react with an inorganic phosphate and with the participation of NAD + (is reduced) to form 1,3-bisphosphoglycerate; it modifies an SH group of the enzyme, which can be reversed by mercaptans.

See also

Categories: Biochemical Reaction | metabolism