Glycolysis

Glycolysis is the initial metabolic pathway of carbohydrate catabolism. The most common and well-known form of glycolysis is the Embden -Meyerhof pathway. The term can be taken to include alternative pathways, such as the Entner-Doudoroff Pathway. However, glycolysis will be used here as a synonym for the Embden-Meyerhof pathway.

Glycolysis is the most universal process by which cells of all types derive energy from sugars. It is not the most efficient, but glycolysis proper is completely anaerobic; that is, oxygen is not required.

Output

Glycolysis converts one molecule of glucose into two molecules of pyruvate, along with "reducing equivalents" in the form of the coenzyme NADH.

The global reaction of glycolysis is:

Glucose + 2 NAD⁺ + 2 ADP + 2 P_i → 2 NADH + 2 pyruvate + 2 ATP + 2 H₂O + 2 H⁺

So, for simple fermentations, the metabolism of 1 molecule of glucose has a net yield of 2 molecules of ATP. Cells performing respiration synthesize much more ATP but this is not considered part of glycolysis. Eukaryotic aerobic respiration produces an additional 34 molecules (approximately) of ATP for each glucose molecule oxidized.

Location

In eukaryotes glycolysis takes place within the cytosol of the cell (as opposed to the mitochondria, where reactions more closely connected to aerobic metabolism occur). Glucose gets into the cell through facilitated diffusion. In some tissues, skeletal muscle for instance, insulin stimulates this process.

Follow up

The ultimate fate of the pyruvate and NADH produced in glycolysis depends upon the organism and the conditions, most notably the presence or absence of oxygen or other external electron acceptors.

In fermentation, the pyruvate and NADH are anaerobically metabolized to yield any of a variety of products. For example, the bacteria involved in making yogurt simply reduce the pyruvate to lactic acid, whereas yeast produce ethanol and carbon dioxide.

In aerobic organisms, the pyruvate typically enters the citric acid cycle, and the NADH is ultimately oxidized by oxygen during oxidative phosphorylation. Although human metabolism is primarily aerobic, under anaerobic conditions, for example in over-worked muscles that are starved for oxygen, pyruvate is converted to lactate, as in many microorganisms.

Evolution

Glycolysis is the only metabolic pathway common to nearly all living organisms, suggesting great antiquity; it may have originated with the first prokaryotes, 3.5 billion years ago or more.

Pathway

The first step in glycolysis is phosphorylation of glucose by hexokinase (in liver the most important hexokinase is glucokinase which has slightly different properties than the hexokinases in most other cells). This reaction consumes 1 ATP molecule, but the energy is well spent: although the cell membrane is permeable to glucose because of the presence of glucose transport proteins, it is impermeable to glucose 6-phosphate. Glucose 6-phosphate is then rearranged into fructose 6-phosphate by phosphoglucose isomerase. (Fructose can also enter the glycolytic pathway at this point.)

Phosphofructokinase-1 then consumes 1 ATP to form fructose 1,6-bisphosphate. The energy expenditure in this step is justified in 2 ways: the glycolytic process (up to this step) is now irreversible, and the energy supplied to the molecule allows the ring to be split by aldolase into 2 molecules - dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. (Triosephosphate isomerase converts the molecule of dihydroxyacetone phosphate into a molecule of glyceraldehyde 3-phosphate.) Each molecule of glyceraldehyde 3-phosphate is then oxidized by a molecule of NAD⁺ in the presence of glyceraldehyde 3-phosphate dehydrogenase, forming 1,3-bisphosphoglycerate.

In the next step, phosphoglycerate kinase generates a molecule of ATP while forming 3-phosphoglycerate. At this step glycolysis has reached the break-even point: 2 molecules of ATP were consumed, and 2 new molecules have been synthesized. This step, one of the two substrate-level phosphorylation steps, requires ADP; thus, when the cell has plenty of ATP (and little ADP) this reaction does not occur. Because ATP decays relatively quickly when it is not metabolized, this is an important regulatory point in the glycolytic pathway. Phosphoglyceromutase then forms 2-phosphoglycerate; enolase then forms phosphoenolpyruvate; and another substrate-level phosphorylation then forms a molecule of pyruvate and a molecule of ATP by means of the enzyme pyruvate kinase. This serves as an additional regulatory step.

After the formation of fructose 1,6 bisphosphate, many of the reactions are energetically unfavorable. The only reactions that are favorable are the 2 substrate-level phosphorylation steps that result in the formation of ATP. These two reactions pull the glycolytic pathway to completion.

Etymology

From Greek glyk meaning sweet and lysis meaning dissolving.

See also

• Gluconeogenesis
• Krebs cycle
• Anaerobic respiration

External links

• The Glycolytic enzymes in Glycolysis: Protein Data Bank
• Glycolytic cycle with animations
• Metabolism, Cellular Respiration and Photosynthesis - The Virtual Library of Biochemistry and Cell Biology