glycolysis

Glycolysis is the process by which the body produces ATP from Glucose.

The Glucose is first broken apart (Lysis). This allows for one set of enzymes to work on both halves of the Glucose, thus allowing for greater efficiency.

Carbon one of the triose glyceraldehyde is then oxidized. The result is Glycerate

The oxidized triose is then reduced. The hydroxyl group is removed, leading to lactate. Furthur reduction is aerobic, as NAD+ is reused for further oxidization.

Pyruvate molecules are then converted to acetyl coenzyme A and hydrogen and carbon dioxide are released.

Well, lactate is usually only produced after glycolysis for lactic acid fermentation in the abscence of oxygen (if your body is using oxygen too rapidly or if you are a yeast cell). Yes, some ATP is produced during glycolysis, but it is mostly just to convert one molecule of glucose to 2 molecules of pyruvate (producing some ATP and NADH along the way). After glycolysis, the pyruvate is then pumped into the Kreb's cycle, then to the Electron Transport Chain (which is aerobic, not anaerobic), where most of your ATP is produced.

Glycolysis is the splitting or lysis of glucose. It is a multi-step reaction requiring ATP for the first steps but producing a net gain of two ATP molecules for each glucose molecule entering it. Glucose takes place in the cytoplasm of a cell.

1. During phosphorylation, glucose is phosphorylated using two ATP molecules first to hexose phosphate and then to hexose bisphosphate.

2. The hexose bisphosphate is broken down (lysis) to two molecules of triose phosphate.

3. Hydrogen is then removed from the triose phosphate and transferred to the carrier molecule NAD (nicotinamide adenine dinucleotide) and the reduced NAD (NADH₂) is used during oxidative phosphorylation.

4. The oxidised triose phosphate is converted to pyruvate releasing two ATP per molecule.

Glycolysis, or the Embden-Meyerhof Pathway is the process by which most living things obtain energy from the ubiquitous sugar Glucose.

            Embden-Meyerhof-Parnas Pathway
                Glycolysis 

                  Glucose
                     1 ATP
		   |(
                     | >ADP + Pi
                     V
             Glucose-6-Phosphate
                     2
                     |
                     |
                     V
            Fructose-6-Phosphate
                     3 ATP
		     |(               
                     | >ADP + Pi
                     V
          Fructose-1,6-Bisphosphate
                     4
                 _________
                /         \
               /           \
              V             V
Dihydroxy Acetone 5----->   Glyceraldehyde-3-Phosphate
  Phosphate                       Pi_ 6 NAD
                                     \|(               
                                      | >NADH
                                      V      
                             1,3-Bisphosphoglycerate 
                                      7 ADP + Pi
                                      |(
                                      | >ATP
                                      V
                                3-Phosphoglcerate
                                      8
                                      V
                                2-Phosphoglcerate
                                      9
                                      |\_>H2O
                                      V
                               Phosphoenolpyruvate
                                     10 ADP + Pi
                                      |(               
                                      | >ATP
                                      V
                                   Pyruvate

Enzymes
1. Hexokinase or Glucokinase
2. Phosphoglucose Isomerase
3. Phosphofructokinase
4. Aldolase
5. Triose Phosphate Isomerase
6. Glyceraldehyde-3-Phosphate Dehydrogenase
7. Phosphoglycerate Kinase
8. Phosphoglycerate Mutase
9. Enolase
10. Pyruvate Kinase

Products per molecule of Glucose:
2 ATP molecules
2 NADH molecules from reduction of two molecules of NAD
2 Pyruvate molecules

The ATP yielded by the reactions of glycolysis is produced by a mechanism called substrate level phosphorylation. The NADH molecules must be oxidized regenerating NAD so that more glucose can be broken down. There are two possible mechanisms for this regeneration:

Krebs Cycle
In the Krebs Cycle pyruvate is converted to Aceytyl-CoA which undergoes a series of reactions producing more NADH, as well as another electron carrier known as FADH, and a molecule of GTP. The electrons on NADH are then used to produce more ATP during chemiosmosis phosphorylation (also known as Oxidative phosphorylation).

Fermentation
In fermentation pyruvate, or a pyruvate derivative, acts as the terminal electron acceptor. It accepts the high energy electrons on NADH, regenerating NAD. Fermentation can produce a variety of compounds, those prodced depends on the type of organisms. Human fermentation produces lactic acid, yeast can produce ethanol. Some bacterial species produce butane-diol. These types of fermentation are by no means limited to the organisms mentioned, and they are not the only possible fermentation pathways.

Also called the Embden-Meyerhof pathway (for some reason leaving out the third guy, Parnas, who was involved in figuring it out), glycolysis is possibly the single most important metabolic pathway. It involves the breaking down of glucose and other simple sugars for energy. It is also explained in a song called In Praise of E.M.P.

This pathway is common to all forms of life on this planet. Individual forms of the enzymes involved are different, but what they do is essentially the same.

The net result of glycolysis is the breaking down of glucose into two molecules of pyruvate and the formation of two molecules of ATP. What happens to the pyruvate next depends on the organism and whether free oxygen is available.

If there no oxygen, pyruvate will be reduced into either lactic acid or ethanol, depending on the organism. This is why yeast makes alcohol. If there is (and the organism can use it), the pyruvate is turned into acetyl CoA and goes on into the TCA cycle (also called the citric acid cycle or the Krebs cycle).

So here's what happens in glycolysis. Further details of regulatory and catalytic mechanisms will be given in the enzyme write-ups.

1. Glucose to glucose-6-phosphate (G6P)
   • catalysed by hexokinase or glucokinase
   • ATP hydrolysed into ADP
   • regulation: hexokinase is allosterically inhibited by high concentration of G6P
2. G6P to fructose-6-phosphate (F6P)
   • catalysed by phosphoglucoisomerase
   • reversible reaction
3. F6P to fructose-1,6-bisphosphate (F-1,6-BP or FBP, previously called fructose diphosphate, so also FDP)
   • catalysed by phosphofructokinase
   • ATP to ADP
   • regulation: complex and very important. This is the step that really controls the rate of glycolysis.
     • inhibited by citrate
     • inhibited by high concentrations of ATP
     • ATP's inhibition is countered by high concentrations of AMP
     • fructose-2,6-bisphosphate (F-2,6-BP) both counters this inhibition and enhances the reaction on its own
4. FBP to dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P)
   • catalysed by fructose bisphosphate aldolase
   • reversible reaction
   • all further reactions are happening in duplicate
5. DHAP to G3P
   • catalysed by triose phosphate isomerase
   • important because only G3P can go on to the next step
   • reversible reaction, but as G3P disappears, equilibrium shifts so more is made from DHAP
6. G3P to 1,3-bisphosphoglycerate (BPG)
   • catalysed by glyceraldehyde-3-phosphate dehydrogenase
   • phosphate added
   • NAD reduced to NADH
   • reversible reaction
7. BPG to 3-phosphoglycerate (3-PG)
   • catalysed by phopsphoglycerate kinase
   • ADP to ATP
   • reversible reaction
8. 3-PG to 2-phosphoglycerate (2-PG)
   • catalysed by phosphoglycerate mutase
   • reversible reaction
9. 2-PG to phosphoenolpyruvate (PEP)
   • catalysed by enolase
   • water released
   • reversible reaction
10. PEP to pyruvate
    • catalysed by pyruvate kinase
    • ADP to ATP
    • regulation:
      • activated by AMP and F-1,6-BP
      • inhibited by ATP, acetyl CoA, and alanine

Other sugars can also be used in glycolysis. Mannose, which is very similar to glucose, can be phosphorylated and then converted into F6P.

Fructose, however, is not directly made into F6P. Instead it is made into fructose-1-phosphate, which is then broken into DHAP and glyceraldehyde, both of which can be turned into G3P.

Galactose is a more unusual case. It must be phosphorylated at the first carbon (making gal-1-P) and then replace glucose-1-P on uridine diphosphate (UDP). The G1P can be turned into G6P, and the galactose on UDP is coverted to glucose, so it can be freed when the next galactose comes along.

Glycolysis is the sequence of reactions that converts glucose into pyruvate with the concomitant production of a relatively small amount of ATP.

Glycolysis can be carried out anerobically (in the absence of oxygen) and is thus an especially important pathway for organisms that can ferment sugars. For example, glycolysis is the pathway utilized by yeast to produce the alcohol found in beer. Glycolysis also serves as a source of raw materials for the synthesis of other compounds. For example, 3 phosphoglycerate can be converted into serine, while pyruvate can be aerobically degraded by the Krebs or TCA cycle to produce much larger amounts of ATP.

There are 5 important types of reactions that occur in glycolysis:

1. phosphoryl transfer: a phosphoryl group is transferred from ATP to a glycolytic intermediate, or from the intermediate to ADP, by a kinase. This reaction is characterized by the transfer of the phosphoryl group from ATP to an alcohol. The alcohol gives up the hydrogen while ADP and an organic phosphate are yielded.

2. phosphoryl shift: a phosphoryl group is shifted from one oxygen atom to another within a molecule by a mutase. This reaction is characterized by the movement of a phosphoryl group from oxygen to an alcohol oxygen in the same molecule. The alcohol hydrogen is removed and binds to the formerly phosphorous-bound oxygen. The original compound's chemical nature can be extensively altered by this shift.

3. isomerization: the conversion of a ketose to an aldose, or vice versa, by an isomerase. In the ketose-aldose conversion, the alcohol hydrogen is transferred to the carbonyl group, thus transforming the original alcohol group to a carbonyl and the original carbonyl to an alcohol. The exact reverse is true for an aldose-ketose isomerization.

4. dehydration: the removal of water by a dehydratase. This reaction is characterized by the removal of a water molecule from an alcohol. This yields a carbon-carbon double bond in the original molecule.

5. aldol cleavage: the splitting of a carbon-carbon bond in a reversal of an aldol condensation by an aldolase. This reaction is characterized by the splitting of a carbon-carbon bond. This yields an aldehyde and a ketose.

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From the BioTech Project at http://biotech.icmb.utexas.edu/. For further information see the BioTech homenode.