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Introduction

This lecture presents a review of anaerobic metabolism.

Glycolysis - overview

Glucose is metabolised in the cell through glycolysis, also know as the Embden-Meyerhoff Pathway

"Glycolysis is the primary pathway for anaerobic degradation of D-glucopyranoses and other D-hexopyranoses. It is probably universal among organisms: certainly the enzymes which catalyze the pathway's reactions are among the most conserved (and therefore presumably most ancient) among proteins." (Quoted from ref. 3 below).

Under anaerobic conditions, glycolysis is a self-contained process leading to the production of fermentation products which vary from organism to organism. In mammalian cells, the primary product is lactate; in yeasts, ethanol and CO₂. The process can be split into several stages:

• "Activation" of glucose
• Glucose is first phosphorylated to form glucose-6-Pi, then isomerised into fructose-6-Pi. The phosphorylation reactions requires ATP. This series of reactions serves two main purposes:
• the glucose is "activated" so as to be able to enter the pathway;
• the glucose is removed from solution in the cytoplasm, thus lowering the concentration and favoring the transport gradient into the cell.
• Formation of triose phosphates
• The fructose-6-Pi is phosphorylated again to give fructose-1,6-bisphosphate, using another ATP, and then split into two triose-Pi molecules, dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-Pi, using the enzyme aldolase. The triose phosphates are interconvertible through triose phosphate isomerase.
• Substrate level phosphorylation through oxidation of glyceraldehyde-3-phosphate
• Glyceraldehyde-3-Pi is oxidized in a reaction in which phosphate is bound, and NAD⁺ is reduced to NADH. The free-energy of the oxidation reaction is used to form a phosphate bond with a high negative free energy of hydrolysis (a "high-energy" bond). The 1,3-bisphosphoglycerate is then converted to 3-phosphoglycerate by a kinase reaction in which the "high-energy" phosphate on the carboxylate end is transfered to ADP to form ATP.
• ATP synthesis linked to conversion of phosphoenolpyruvate to pyruvate
• 3-phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase, and then dehydrated to give phosphoenolpyruvate, using the enzyme enolase. This converts the phosphate bond at the 2-position to a "high-energy" bond.
• The phosphoenolpyruvate reacts with ADP to form ATP and pyruvate, using pyruvate kinase
• Reduction of pyruvate to regenerate NAD⁺
• In order to restore the NAD⁺ used up in glyceraldehyde-3-Pi oxidation, the pyruvate is reduced to lactate using NADH

The net yield of anaerobic glycolysis is 2ATP / glucose, with an overall reaction:

Central Role of ATP in energy metabolism

The conversion between ATP, and ADP and phosphate, plays a central role in the energy metabolism of the cell. The poise of the reaction in a metabolic compartment plays a determining role in the direction of metabolism, either directly through thermodynamics, or indirectly through the activating (or inhibitory) effects on enzymes.

Compartmentalization of the eukaryote cell

• Cytoplasmic metabolism probably reflects an archeal origin
• Mitochondrial structure and eubacterial origin
• The Virtual Cell
• Distribution of metabolic activities between cytoplasmic and mitochondrial compartments

Useful Links

Glycolysis

1. A nice introduction to glycolysis
   

2. A clickable pathway with biochemical information, PDB files of enzymes^*
   
3. Glycolysis in a Chime tutorial.
4. A clickable metabolic web representation of glycolysis, which provides links to reaction parameters, physical chemistry, PDB files of intermediates^*, etc.(The Klotho project)
   ^*(You will need a viewer to see Brookhaven Protein Data Bank (PDB) structural files. If you use Netscape, you can download Rasmol (a stand-alone viewer) or Chime (a plug-in) by clicking here. Download Rasmol, or Chime plug-in)
   
5. What Is There? (WIT- a successor to the PUMA project).
6. A text version with clickable reactions
   
7. A colorful summary of glycolysis and the citric acid cycle