GLYCOLYSIS

GLYCOLYSIS

The official spokesperson of carbohydrate metabolism ,'glucose', speaks:

"I burn myself to provide fuel to life!

Generated through gluconeogenesis by my friends;

Engaged in the synthesis of lipids, amini acids;

Deranged in my duties due to diabetes melitus."

INTRODUCTION

• Glycolysis is derived from the Greek words (g;lycose- sweet or sugar; lysis -dissolution).
• Universal pathway in the living cells.
• This pathway is often referred to as Embden Meyerhof pathway (E.M. pathway).

Definition: 

Glycolysis is defined as the sequence of reactions converting glucose(or glycogen) to pyruvate or lactate, with the production of ATP.
what i am gonna do now is try to make it more interesting for you guys to understand this topic..
it will be a brief conversation between 2 people so lets see how it goes.

Fun way to understand glycolysis

The conversation between two people to make you guys understand glycolysis more efficiently.

GAJENDRA: Divyani, if you had a daughter,what first name would you pick for her?

DIVYANI: Maybe Samaya. What about you?

GAJENDRA: I think I would choose Glycis. It's a Greek first name and it means sweet. Glycis is also the origin of the word glycolysis. Lysis, also derived from the Greek, and means breaking down.

 I think if my hypothetical daughter was prone to breaking things, I could give her Glycolysis as a nickname.

 But more seriously, glycolysis is a very good name for a process that breaks down glucose, a simple hexos, into two molecules of pyruvate, each containing three carbons.

DIVYANI: We shouldn't forget that glycolysis produces ATP too.

GAJENDRA: You're right. Glycolysis is responsible for the synthesis of ATP in most, if not all, living organisms. Pyruvate is also important because it is at the crossroad of many metabolic pathways, serving as a precursor for the synthesis of several biomolecules, and for the production of a large number of ATP molecules under aerobic conditions.

DIVYANI: You said that glycolysis is found in most, if not all, living organisms. I thought glycolysis was the universal pathway of glucose metabolism in living organisms.

GAJENDRA: I did not use the word universal, because if some of our students 'chercher la petite bête' as we say in France, that is if they split hairs or nit pick, they might discover that some microorganisms lack one or more glycolytic enzymes, we assume that in these microorganisms a variant of glycolysis exists

.

DIVYANI: Are glycolytic enzymes the same in most species?

GAJENDRA: They are very similar across species from human to plants and simple microorganisms. Because life emerged in an environment devoid of oxygen, glycolysis, which does not require oxygen, is likely an extremely ancient pathway. Its fundamental role at the core of cell metabolism explains the conservation of glycolytic enzymes across species.

Even organisms like humans, that cannot survive without oxygen, have tissues and cell types where glycolysis is the sole, or most dominant, pathway to produce ATP. Red blood cells, for example, rely exclusively on glycolysis for their ATP production.

DIVYANI: Are the terms fermentation and glycolysis interchangeable?

GAJENDRA: No, fermentation is defined as the anaerobic degradation of fuel molecules, including glucose, to obtain energy. Glycolysis is only one step of the fermentation process. Fermentation includes also the degradation of the end products of glycolysis, pyruvate, under anaerobic conditions.

DIVYANI: What does happen to pyruvate under aerobic conditions?

GAJENDRA: Pyruvate is completely degraded in carbon dioxide and water during the citric acid cycle and oxidative phosphorylation. The complete oxidation of glucose into carbon dioxide and water is very exergonic. The free energy change is minus 2,840 kilojoules per mole.

 Debu, where do you keep the sugar in your kitchen?

DIVYANI: In a sugar bowl. Why?

GAJENDRA: Table sugar is in fact a disaccharide made of glucose and fructose. So you don't keep your sugar in a tightly closed, oxygen depleted, container. Aren't you afraid that your sugar will spontaneously combust?

DIVYANI: No, remember that even spontaneous reactions are extremely slow. The oxidation of the sugar in my kitchen would take forever. During glycolysis, the oxidation of glucose into pyruvate

is a quick process, because enzymes accelerate each step of glycolysis.

GAJENDRA: You made a good point Debu. Now let's be destructive and show us how glucose is broken down in our cells.

DIVYANI: During glycolysis, the conversion of one molecule of glucose into two molecules of pyruvate is achieved in 10 steps. 

The first step is the phosphorylation of glucose on carbon 6 to form glucose-6-phosphate. This reaction, which is catalyzed by hexokinase, consumes one molecule of ATP.

GAJENDRA: Wait a minute. I thought that glycolysis produced ATP, but right from the start 1

ATP is consumed?

DIVYANI: Yes, but more ATP will be produced later. You'll see that during the first five steps, called the preparatory phase, 2 molecules of ATP are consumed. If we were teaching an economics course I would say that 2 ATP are invested. In the second phase of glycolysis, called the payoff phase, you get a good return on your investment.

GAJENDRA: I hope so, but why is glucose phosphorylated?

DIVYANI: While glucose can enter or exit cells via specific transporters, there is no transporter for glucose-6-phosphate. The phosphorylation traps glucose inside the cell.

GAJENDRA: What happens next?

DIVYANI: In the second step, glucose-6-phosphate is isomerized into fructose-6-phosphate. First, glucose-6-phosphate is linearized and then the carbonyl group is moved from carbon 1 to carbon 2.

Finally, there is cyclization in release of fructose-6-phosphate from the phosphohexose isomerase, the enzyme that catalyzes this reaction.

GAJENDRA: Let me guess, the isomerization frees carbon 1 that can now be phosphorylated like carbon 6 was phosphorylated in the glucose molecule?

DIVYANI: Exactly. That is when our second ATP molecule is consumed. Fructose-1,6-bisphosphate is produced. The very tightly controlled enzyme called phospho-fructokinase 1 catalyzes the reaction.

GAJENDRA: Is the second phosphorylation also meant to trap the phosphorylated sugar inside the cell?

DIVYANI: No. The second phosphate de-stabilizes the molecule by bringing two negatively charged groups in close proximity. In addition, the binding energy released by the interaction of both phosphates with the active side of the enzyme, called aldolase, reduces the enzyme's activation energy, and facilitates the cleavage of fructose-1,6-bisphosphate into to triosphosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.

 Once again, the first step is the opening of the ring structure. The position of the carbonyl group of carbon 2 in the linear molecule will determine the position of the cleavage to form the two triose phosphates.

GAJENDRA: We started with a single molecule of glucose, and now we have two completely different trails. Does it mean the glycolysis is a branch pathway?

DIVYANI: No. In fact, the fifth and last reaction of the preparatory phase is an intraconversion of the triose phosphates. Because only glyceraldehyde 3-phosphate is directly degraded in the second phase of glycolysis, the intraconversion equilibrium is pushed toward the conversion of dihydroxyacetone phosphate into glyceraldehyde 3-phosphate.

GAJENDRA: OK. It's payoff time.

DIVYANI: Exactly, we now enter the payoff phase. During the sixth reaction, glyceraldehyde 3-phosphate is oxidized to form 1,3-bisphosphoglycerate. This time, the new phosphate group does not come from the hydrolysis of ATP, but an inorganic phosphate is attached. The reaction is coupled with the reduction of NAD+ into NADH plus a proton. The phosphate is bound to a carboxylic acid group to form an acyl phosphate with a very high standard free energy of hydrolysis. The Delta G for the hydrolysis reaction is negative 49.3 kilojoules per mole.

GAJENDRA: I suppose that the hydrolysis of the acyl phosphate is coupled to the synthesis of one molecule of ATP.

DIVYANI: Correct, but two molecules of ATP, and not one, are formed. Remember that the initial glucose molecule has been cleaved, and for each glucose molecule entering glycolysis, two molecules of 1,3-bisphosphoglycerate are produced. The reaction produces 2 ATP molecules and 2 3-phosphoglycerate molecules. This type of ATP synthesis is called substrate level phosphorylation. 

Now the eighth reaction is the conversion of 3-phosphoglycerate into 2-phosphoglycerate. By moving the phosphate group from carbon 3 to carbon 2 and hydrogen in a hydroxyl group carried by carbon 2 and carbon 3 respectively, can be the target of a dehydration reaction.

 This ninth reaction leads to the formation of phosphoenol-pyruvate.

GAJENDRA: Wouldn't the formation of ATP by transferring the phosphates from 2-phosphoglycerate to ADP be more efficient?

DIVYANI: Not really. Phosphoenol-pyruvate has a standard free energy of hydrolysis 3 and 1/2 times higher than that of 2-phosphoglycerate.

 The formation of phosphoenol-pyruvate facilitates the synthesis of ATP during the last step of glycolysis, leading to the formation of ATP in pyruvate. Half of the energy released by the hydrolysis of phosphoenol-pyruvate is used to form ATP, and the other half drives the reaction towards ATP synthesis.

GAJENDRA: Debu, it is now time to check the return on our investment.

DIVYANI: Yes, we started with 1 glucose, 2 NAD+, 2 ADP, 2 ATP, and 2 inorganic phosphates.

We ended up with 2 pyruvates, 2 NADH, and 2 protons, 4 ATP and two water molecules. Overall, a molecule of glucose produces 4 minus 2, equals 2 molecules of ATP.

GAJENDRA: That's nice. Not very impressive I must admit.

DIVYANI: Remember, glucose has not been fully oxidized, since the pyruvate was the end product and not carbon dioxide. Under aerobic conditions, pyruvate will be fully oxidized by a different pathway, and over 30 molecules of ATP will be produced per molecule of glucose.

GAJENDRA: That's much better. Now I feel sorry for anaerobic organisms that mostly rely on glycolysis to produce ATP. They must have to consume higher quantities of fuel molecules.

DIVYANI: We'll leave that story for another time.

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