Glycolysis Process-Function Links

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Initial comments:

GO term:glycolysis

GO id:GO:0006096

Definition:The chemical reactions and pathways resulting in the breakdown of a monosaccharide (generally glucose) into pyruvate, with the concomitant production of a small amount of ATP. Pyruvate may be converted to ethanol, lactate, or other small molecules, or fed into the TCA cycle.

 Comment from Chris: If it is NOT glucose, then do the has_part relations below still hold?)

This has two is_a children:

GO term:anaerobic glycolysis

Synonym: modifed Embden-Meyerhof pathway

GO id:GO:0019642 Definition: NONE GIVEN!!!


and


GO term:Embden-Meyerhof pathway

Synonym: Embden-Meyerhof-Parnas pathway

GO id:GO:0019641

Definition:The main pathway for anaerobic degradation of carbohydrates. Starch or glycogen is hydrolyzed to glucose 1-phosphate and then through a series of intermediates, yielding two ATP molecules per glucose and producing either pyruvate (which feeds into the tricarboxylic acid cycle) or lactate.

 comment from Chris: surely this is a problem? Surely EM pathway should be an is_a child
 of anaerobic glycolysis? I would expect:
 Glycolysis+ Aerobic+ Anaerobiv++ EM pathway++ ???Genus differentia definitions definitely help!
 comment from Midori: I'm not so sure -- looking at MetaCyc's pathways and synonyms,
 I think it's possible that it's the existing GO term names and text definitions that are off.
 We should investigate what "Embden-Meyerhof pathway" really refers to.
 comment from Peter: Of the reliable biochemitry textbooks I know, only two use the 
 term "Embden-Meyerhoff pathway", and both use it as an exact synonym for glycolysis:
 Stryer "Biochemistry" 4th ed (1995) - page 484. "The complete glycolytic pathway was
 elucidated in 1940 ... . Glycolysis is also known as the Embden-Meyerhof pathway."
 Metzler "Biochemistry" (1977) - page 540. "The sequence of reactions in glycolysis
 (the Embden-Meyerhof-Parnas pathway) soon became clear."
 

Note that Reactome begins glycolysis with G6P to F6P in both plants and animals, as does your series of steps below. So there is no disagreement? Just checking.

 comment from Peter: The only CURATED version of glycolysis in Reactome is the
 human one, and that one does in fact begin from glucose. Any statements in Reactome
 about glycolysis for other species, e.g., Arabidopsis or Oryza (rice) are 
 electronically inferred from the human pathway on the basis of existence of 
 (apparently) homologous proteins in the other species.


Actually, most of the steps of GO:0019641 are included in glycolysis, but not the first steps That is: EM pathway has parts that are not necessarily held by glycolysis


There are several ways to get G-6P, actually two basic ways; either from free glcose

a. Hexokinase: G + ATP -> G-6P

b. Glycogen Phosphorylase catalyzes phosphorolytic cleavage of the a(1®4) glycosidic linkages of glycogen, releasing glucose-1-phosphate as the reaction product. Phosphoglucomutase then catalyzes the reversible reaction: Glucose-1-phosphate to Glucose-6-phosphate; so hexokinase is not used here; thus, I do not count hexokinase as a required step in what we call glycolysis.

c. Starch; muliple glucose linked with 1-4 alpha, aka soluble starch, is broken down via alpha-amylase into maltose (2 subunits of glucose) and then further broken down to glucose, which then is activated via reaction “a”

d. cellulose: beta 1-4 links; bacteria and plants, and fungi: glycoside hydrolases.

Some textbooks include hexokinase as a step in glycolysis,but note that it is not the only way to get G6P, and therefore, I start glycolysis after hexokinase.


Glycolysis :


Step 1Is it worthwhile recording reactome IDs for each step?. conversion of glucose 6-PO4 into fructose 6-PO4

GO term:glucose-6-phosphate isomerase activity

Synonyms: D-glucose-6-phosphate aldose-ketose-isomerase activity, D-glucose-6-phosphate ketol-isomerase activity, glucose phosphate isomerase activity, hexose monophosphate isomerase, activity, hexose phosphate isomerase activity,hexosephosphate isomerase activity, oxoisomerase activity, phosphoglucoisomerase activity, phosphoglucose isomerase activity, phosphohexoisomerase activity, phosphohexomutase activity, phosphohexose isomerase activity, phosphosaccharomutase activity

GO id:GO:0004347

Definition:Catalysis of the reaction: D-glucose 6-phosphate = D-fructose 6-phosphate.


Step 2. conversion of fructose-6P to fructose1,6P

GO term:6-phosphofructokinase activity

GO id:GO:0003872

Definition:Catalysis of the reaction: ATP + D-fructose 6-phosphate = ADP + D-fructose 1,6-bisphosphate.


Step 3.convert the 6-carbon unit to two 3-carbon units

GO term:fructose-bisphosphate aldolase activity

Synonym: 1,6-diphosphofructose aldolase activity, aldolase activity, D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase (glycerone-phosphate-forming)

GO id:GO:0004332

Definition:Catalysis of the reaction: D-fructose 1,6-bisphosphate = glycerone phosphate (aka dihydroxyacetone -P) + D-glyceraldehyde 3-phosphate.


Step 4. how to convert all 3-C units to 3Glyceraldehyde-P

GO term:triose-phosphate isomerase activity

Synonym: phosphotriose isomerase activity, triose phosphate mutase activity, triose phosphoisomerase activity, triosephosphate isomerase activity, triosephosphate mutase activity

GO id:GO:0004807

Definition:Catalysis of the reaction: D-glyceraldehyde 3-phosphate = glycerone phosphate.


5. Convert the 3 Glyceraldehyde P to 1,3GP (ak 1,3 diphosphoglyceric acid) from inorganic phosphate

GO term:glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) activity

Synonym: 3-phosphoglyceraldehyde dehydrogenase activity, GAPDH activity, glyceraldehyde phosphate dehydrogenase (NAD), glyceraldehyde-3-P-dehydrogenase activity, NAD-dependent glyceraldehyde-3-phosphate dehydrogenase activity

GO id:GO:0004365

Definition:Catalysis of the reaction: D-glyceraldehyde 3-phosphate + phosphate + NAD+ = 3-phospho-D-glyceroyl phosphate + NADH + H+. (aka1,3 diphosphoglyceric acid)


Step 6. Now need take 1,3 diphosphoglyceric acid and make ATP and 3 phosphoglyceric acid (3GP)

GO term:phosphoglycerate kinase activity

Synonym: 3-PGK, 3-phosphoglycerate kinase activity,3-phosphoglycerate phosphokinase activity, 3-phosphoglyceric acid kinase activity, 3-phosphoglyceric acid phosphokinase activity, 3-phosphoglyceric kinase activity, glycerate 3-phosphate kinase activity, glycerophosphate kinase activity,PGK, phosphoglyceric acid kinase activity, phosphoglyceric kinase activity, phosphoglycerokinase activity

GO id:GO:0004618

Definition:Catalysis of the reaction: ATP + 3-phospho-D-glycerate = ADP + 3-phospho-D-glyceroyl phosphate (aka 1,3 diphosphoglyceric acid


Step 7 Now take 3GP and convert it to 2GP

GO term:phosphoglycerate mutase activity

Synonym: bisphosphoglyceromutase,D-phosphoglycerate 2,3-phosphomutase activity, diphosphoglycomutase, GriP mutase, monophosphoglycerate mutase activity, monophosphoglyceromutase activity, MPGM, PGA mutase activity, PGAM activity, PGM, phosphoglycerate phosphomutase activity, phosphoglyceromutase activity

GO id:GO:0004619

Definition:Catalysis of the reaction: 2-phospho-D-glycerate = 3-phospho-D-glycerate.


Step 8. Now take 2GP and make it PEP (phosphopyruvate)

GO term:phosphopyruvate hydratase activity

Synonym: 14-3-2-protein, 2-phospho-D-glycerate hydro-lyase (phosphoenolpyruvate-forming), 2-phosphoglycerate enolase activity, 2-phosphoglyceric dehydratase activity,enolase activity

GO id:GO:0004634

Definition:Catalysis of the reaction: 2-phospho-D-glycerate = phosphoenolpyruvate + H2O.


9: Convert PEP to pyruvate and get 1 ATP out

GO term:pyruvate kinase activity

Synonym: ATP:pyruvate 2-O-phosphotransferase activity,phosphoenol transphosphorylase activity, phosphoenolpyruvate kinase activity

GO id:GO:0004743

Definition:Catalysis of the reaction: ATP + pyruvate = ADP + phosphoenolpyruvate.

Reverse reaction occurs in glycolysis. I think we have to consider the implications of this.


This is the last step of glycolysis shared by all the various subtypes of glycolysis‚


In anaerobic systems, pyruvate cannot be further oxidized.

In yeast, pyruvate is converted to acetaldehyde by pyruvate decarboxylase, and then ethanol is produced from acetaldehyde and NADH (the reverse reaction of alchohol deydrogenase).

I believe that what happens to the pyruvate aftewards should not be grouped into glycolysis.

 comment from Midori: I agree!

In mammals, pyruvate can be disposed of in two ways

anaerobically:

Pyruvate + NADH is converted to lactate +NAD (reverse of lactate dehydrogenase).


or Aerobically: pyruvate dehydrogenase

Pyruvate + NAD+ CoA = Acetyl-CoA +NADH+CO2

This goes on to the TCA cycle

 comment from Peter: Or into de novo syntheis of long-chain fatty acids (that's how
 a high-calorie, low-fat diet makes you fat). These multiple possible functionally 
 diverse fates of pyruvate are a good rationale for calling pyruvate the end product
 of glycolysis.

There should be a term in BP for this

(or, pyruvate can carboxylated (PDC) t

Pyruvate + CO2 + ATP = Oxaloacetate + ADP + PI

 comment from Peter: True, but this is a reaction of gluconeogenesis (de novo glucose
 synthesis), not of glycolysis (glucose catabolism) and in a normal human or chicken 
 (or, probably, mouse or rat), the pyruvate molecules that undergo carboxylation to 
 form oxaloacetate do not derive directly from glucose, but rather are generated by
 transamination of alanine or by import and oxidation of lactate.

Oxoaloacetate condenses with Acetyl-CoA in the 1st step of the TCA cycle, to give citrate. Again, these are not part of glycolysis, but are involved in what to do with the pyruvate once formed.