Hello biochemistry freaks. Its been a while since I’ve posted anything, the reason being is that I had so much work to do in the past few weeks and little by little I did a little something everyday until I was ready to post something worth reading. This next topic is about Glycolysis so here I go enjoy! J
GLYCOLYSIS WAS THE FIRST METABOLIC PATHWAY TO BE UNRAVELLED BY G.Embden, O.Meyerhof and J,Parnas! Sigh…. some tedious men at work that figured out the 10 reactions.J
‘glyco’-glucose and ‘lysis’-split gives you a basic idea of what glycolysis is all about and is said to be dated as to when there was anaerobic environments still years ago in the atmosphere.
This series of reactions consists of two phases (energy investment phase/preparatory phase and energy payoff phase) and 10 enzymes with 5 in each phase. The reactions for each phase are as follows:
Consists of 5 enzymes:
3.Phospho-fructose kinase 1
5.Triose phosphate isomerase.
You must observe that 2 reactions ARE UNI DIRECTIONAL (involving 1 AND 2) due to a large negative change of free energy(energergetically unfavourale). Also 2 ATP are lost in these r’xns. These two reactions are called the 1st priming and 2nd priming reactions respectively.The remaining reactions are reversible.
1st reaction/1st priming r’xn :
A phosphate group (phosphorylation) is added to carbon 6 on glucose to form glucose 6 phosphate. This is catalyzed by Hexokinase (a type of transferase transferring terminal phosphate group from ATP to glucose). Hexo-6 kinase- taking the terminal phosphate group from ATP. IN THIS R’XN 1 ATP IS LOST!! THIS REACTION IS IRREVERSIBLE!! Reason: delta G value has a high negative value……..
*Note : Why convert to gl- 6 phosphate though?
Ans: by phosphorylating the glucose you trap it in the cell as there are no transporters in the cell membrane for this as it would have for glucose.
*Note : all kinases need mg2+ in active site….WHY??? ANS. It stabilizes the negative charge on ATP molecule. Also it stabilizes the conformation of the enzyme and it prevents the hydrolysis of the ATP by keeping water out.
Phospho-hexose isomerase enzyme converts glucose6-phos. to fructose -6- phos. AN ALDOSE SUGAR IS CONVERTED TO A KETOSE SUGAR. THIS IS A REVERSIBLE REACTION.
3rd reaction/ 2nd priming reaction:
Catalyzed by PFK1. This enzyme is the most regulated enzyme in glycolysis. ATP IS LOST HERE AGAIN as f-6-phos. is converted to fructose-1-6-bisphosphate. The phosphate groups are not attached to the same carbon atom thus bi- is used rather than di-.. THIS IS A IRREVERSIBLE REACTION!!
Catalysed by Aldolase . In this reaction f-6-phos[hate is split into glyceraldehyde 3-phosphate (G3P) + dihydroxyacetone phosphate (DHAP). Two 3-carbon structures are formed. THIS IS A REVERSIBLE REACTION.
DHAP is converted to G3P. This is catalyzed by triose phosphate isomerase. *note: it is said that this enzyme is a kinetically perfect enzyme meaning that as substrate bund too the enzyme a reaction happens. The reaction happens fast , its intermediate is very unstable.
THE PAYOFF PHASE:
The 5 enzymes involved are:
6.Glyceraldehyde 3-phosphate dehydrogenase
7.Phospho glycerate kinase
8.Phospho glycerate mutase
2 G-3-p converted to 2 molecules 1,3bsphosphateglycerate(1,3 BPG). This is a reversible reaction. 2 phosphate are used to energise the conversion and 2 molecules of NAD+-NADH formed. OXIDATION AND PHOSPHORYLATION OCCURS. Oxidation is nad –nadh where the g 3 p lost hydrogen so it is oxidized. Phsphorylation (atp is not used here but inorganic source), the oxidation reaction produces the energy need to add the phosphate group. THIS REACTION CONTAINS THE ONLY OXIDATION REACTION IN GLYCOLYSIS.
*note: glycolysis would not occur without NAD+. It needs to be converted to NADH.
1,3 BPG converted to 2 molecules 3-phosphoglycerate. 1ST ATP FORMED HERE (2 are formed) !!. SUBSTRATE LEVEL PHOSPHORYLATION OCCURS HERE. Catalyzed by phosphoglycerate kinase. Phos. comes from the substrate 1,3 BPG leaving 3-ph glycerate.
*note: the 2 ATP used in investment phase is paid back here.
Catalysed by ph g’te mutase (enz 8 above). In this reaction the 3-phos.g’te is first converted to 2molecules of 2,3 bisphosphate glycerate. Then the phosphate on carbon 3 is removed finally forming 2-phos.glycerate.
The product above is converted to 2 molecules Phosphoenolpyruvate (PEP). WATER IS LOST, THIS IS A HYDROLYSIS REACTION. Catalyzed by enolase. This is an irreversible reaction beacause of delta G value being highly negative.
10th reaction: catalyzed by pyruvate kinase. 2 molecules PEP converted to 2 molecules pyruvate. Substrate level phos. this reaction is the most energeticslly favourable reaction in glycolysis. 2 ATP molecules made THIS IS THE SECOND ATP FORMATION ad is profit ATP.
*note:PEP HAS A LOT OF ENERGY THAT CAN CREATE THEORETICALLY MAKE 2 MOL. ATP FROM EACH BUT ONLY FORMS 1 ATP EACH AS REST OF ENERGY IS LOST AS HEAT. This r’xn is a reason for sweating also when exercising.
*note p.kinase deficiency- erythrocytes cannot get energy from glycolysis. Ery… can only get energy from glycolysis, this condition is aka hemolytic anemia.
2ATP AND 2 NAD+ IS USED THEN 4 ATP AND 2 NADH GENERATED—————>
THEREFORE THERE IS A NET GAIN OF 2 ATP MOLECULES AND 2 MOLECULES NADH
The following picture illustrates the process of glycolysis in good detail:
NOWWW WHAT ARE THE FATES OF THIS PYRUVATE????????????????
Under aerobic conditions the following reaction occur :
Under anaerobic conditions lactate or ethanol fermentation occurs. Fermentation is done for regenerating NAD+ for glycolysis to continue.
For lactate fermentation :
This method is unidirectional an is used by erythrocytes or strenuous exercise(lactic acid formed…needs oxygen to break down L.acid……can cause cramps). ERYTHROCYTES HAS NO MITOCHONDRIA THEREFORE LACTATE FERMENTATION IS USED FOR ENERGY. NO ATP FORMED.THE CELL GETS 2 ATP MOLECULES FOR EACH GLUCOSE MOLECULES USED IN GLYCOLYSIS.
For ethanol fermentation:
NAD+ IS REGENERATED SO GLYCOLYSIS TO CONTINUE.