From Academic Kids
Glycolysis is the initial metabolic pathway of carbohydrate catabolism. The most common and well-known form of glycolysis is the Embden-Meyerhof pathway, initially eludidated by Gustav Embden and Otto Meyerhof. 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. Glycolysis itself is completely anaerobic; that is, oxygen is not required.
The overall reaction of glycolysis is:
- Glucose + 2 NAD+ + 2 ADP + 2 Pi → 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. Unlike those molecules of ATP produced by aerobic respiration, those of glycolysis are produced by substrate-level phosphorylation.
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 enters the cell through facilitated diffusion. In many tissues, including skeletal muscle, insulin stimulates this process.
In fermentation, the pyruvate and NADH are anaerobically metabolized to yield any of a variety of products with an organic molecule acting as the final electron acceptor. 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 (also known as the TCA or Krebs 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 of oxygen, pyruvate is converted to lactate, as in many microorganisms.
Glycolysis is highly conserved in evolution, being common to nearly all living organisms. This suggests great antiquity; it may have originated with the very first prokaryotes, 3.5 billion years ago or more.
The first step in glycolysis is phosphorylation of glucose by hexokinase to form glucose 6-phosphate (G-6-P). In the liver an isozyme of hexokinase called glucokinase is used, which differs primarily in regulatory properties. This reaction consumes 1 ATP molecule, but the energy is well spent. The cell membrane is permeable to glucose for two reasons - glucose transporters move glucose across the membrane, and neutrally charged glucose is able to passively diffuse through. G-6-P is negatively charged and this is repelled by the plasma membrane, so this phosphorylation effectively traps glucose in the cell. G-6-P is then rearranged into fructose 6-phosphate (F-6-P) by phosphoglucose isomerase. Fructose can also enter the glycolytic pathway via phosphorylation at this point.
Phosphofructokinase-1 then consumes 1 ATP to form fructose 1,6-bisphosphate (F-1,6-bisP). 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 destablises the molecule, allowing the ring to be split by aldolase into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Triose phosphate isomerase rapidly interconverts these, with glyceraldehyde 3-phosphate proceeding further into glycolysis. 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.
From Greek glyk meaning sweet and lysis meaning dissolving.
- The Glycolytic enzymes in Glycolysis: Protein Data Bank (http://nist.rcsb.org/pdb/molecules/pdb50_1.html)
- Glycolytic cycle with animations (http://www.wdv.com/CellWorld/Biochemistry/Glycolytic)
- Metabolism, Cellular Respiration and Photosynthesis - The Virtual Library of Biochemistry and Cell Biology (http://www.biochemweb.org/metabolism.shtml)