glucose + 2 ADP + 2 Pi + 2 NAD+ yeilds 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O

adp is quickly transformed into atp creating a high energy bond

the most fundamental metabolic pathway

purpose is to generate atp but alsp get other important intermediate compounds

Stages : 1 Energy Investment

2 ATP Production

Synthesis of glucose-6-phosphate

phosphorylation of glucose by hexokinase and Mg2+- co factor foms bridge with negative charges ion atp to stabalize  so enzyme can bind

phosphorylation of glucose prevents transport out of the cell and increases reactivity  

conversion of glucose-6-phosphate to fructose-6-phosphate

conversion of aldose to ketose, isomerization

driven because fructose is consumed or due to build up of glucose 6 phosphate

enzyme is phosphoglucose isomerase

phosphory6 plation of fructose- 6- phosphate

this step is irreversible due to a large decrease in free energy and commits the molecule to glycolysis

enzyme is phosphofructokinase-1 and Mg2+  (PFK-1) - tetrameric enzyme as M4 in muscle and L4 in liver, a major regulatory enzyme that is used to control glycolysis

this is an irreversible step!!!

aldol cleavage of fructose 1,6 bisphosphate  giving an aldose and ketose product

aldolase cleaves fructose 6 phosphate into d glyceraldehyde 3 phosphate and dihydroxyacetone phosphate (not able to undergo glycolysis)  

interconversion of glyceraldehyde 3 phosphate and dihydroxyacetone phosphate

conversion of the ketose dihydroxyacetone phosphate into the aldose glyceraldehyde 3 phosphate  enables all carbons to continue through glycolysis

enxyme- triosephosphate isomerase

oxidation of glyceraldehyde 3 phosphate- results in gulcerate 1 3 bisphosphate

creates high energy phosphoanhydride bond for ATP formation and NADH

this is an oxidation step where g3p is oxidized and nad+ is reduced - energy conserved in the creation of the new phosphate bond as well as in the reducing to NADH

enzyme- glyceraldehyde 3 phosphate dehydrogenase

another step that is not spontaneous but is driven by the use up of the product therefore more product is made following LeChatliers principle

phosphoryl group transfer

production of ATP via substrate level phosphorylation- P is added to ADP from the substrate

enzyme- phosphoglycerate kinase, Mg2+

rxn: glycerate 1 3 bisphosphate to glycerate 3 phosphate

interconversion of glycerate 3 phosphate to glycerate 2 phosphate

first step in formation of phosphoenolpyruvate (PEP)

an isomerization to a less stable molecule

enzyme- phosphyoglycerate mutase, Mg2+

dehydration of glycerate 2 phosphate - endolization

production of PEP which has a high phosphorylgroup transfer potnetial (tautomerization), locks it inot the highest energy form

PEP is very unstable with lots of phosphate group transfer potential

enzyme- enolase, Mg2+

formation of pyruvate and ATP

produces a net of 2 atp, 2 nadh and 2 pyruvate

PEP into pyruvate

reaction is irreversible

another regulatory site of glycolysis

enzyme- pyruvate kinase, Mg2+

Use 2 ATP : glucose to glucose 6 p to furctose 6 p to fructose 1,6 bisp

Produce 4 ATP: glucerate 1,3 bisP to 3 phosphate glucerate to PEP to pyruvate

pyruvate is an energy righ molecule

under aerobic conditions, pyruvate is converted to ace CoA for use in the citric acid cycle and the ETC

createhs lots of high energy molecules- NADH

alcohol fermentation-NADH is oxidizing agent, all H get dumped onto pyruvate is reduced to create alcohol products

under anaerobic conditions pyruvate can undergo germentation: alcoholic or homolactic

regnerates NAD+ so glycolysis can continue

evaluation of free energy changes measured in blood cells shows steps 1,3,and 10 (all kinase reactions- where all the regulation occrus) have significantly negative delta G values and are irreversible

the rest of the steos are close to equilibrium and the direction of reaction can be shifted by changes in substrate concentrations

the inside of a cell does not work with standard free energy!!!

the rate of the glycolytic pathway is controlled by 3 allosteric enzymes

1. Hexokinase

2. PFK 1

3. Pyruvate Kinase

Allosteric enxymes are sensitive indicators of a cell's metabolic state regulated locally by effectors

the hormones glucagon and insulin also regulate glycolysis

high amp concentrations activate PFK 1 and pyruvate kinase

Fructose 2 6 bisphosphate, produced via hormone induced covalent modicitation of PFK 2, activates PFK 1

accumulation of fructose 1 6 bisphosphate activates pyruvate kinase providing a feed forward mechanism