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ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 1: CARBOHYDRATES

G G l l y y c c o o l l y y s s i i s s

B B B Y Y Y

D D R R . . P P O O U U L L A A M M I I A A D D H H I I K K A A R R Y Y M M U U K K H H E E R R J J E E E E A A S S S S I I S S T T A A N N T T P P R R O O F F E E S S S S O O R R

D D E E P P A A R R T T M M E E N N T T O O F F Z Z O O O O L L O O G G Y Y

N N A A R R A A J J O O L L E E R R A A J J C C O O L L L L E E G G E E

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ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 1: CARBOHYDRATES

Glycolysis Definition:

Glycolysis is the central pathway for the glucose catabolism in which glucose (6-carbon compound) is converted into pyruvate (3- carbon compound) through a sequence of 10 steps. In other words, Glycolysis is a metabolic pathway converting glucose into pyruvate, the high energy released is utilized in the formation of ATP and NADH molecules.

 Glycolysis takes place in both aerobic and anaerobic organisms

and is the first step towards the metabolism of glucose.

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 The glycolytic sequence of reactions differs from one species to the other in the mechanism of its regulation and the subsequent metabolic fate of the pyruvate formed at the end of the process.

 In aerobic organisms, glycolysis is the prelude to the citric acid cycle and the electron transport chain, which together release most of the energy contained in glucose.

 It is also referred to as Embden-Meyerhof-Parnas or EMP

pathway, in honor of the pioneer workers in the field.

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Glycolysis Equation:

A A s su u m m ma m a ry r y o o f f t t he h e p p ro r o ce c e s s s s o o f f g g l l yc y co o ly l ys s i i s s ca c an n be b e w w r r i i t t te t en n as a s f f o o ll l lo ow w s: s :

C C

66

H H

1212

O O

6 6

+ + 2 2 AD A DP P + + 2P 2 Pi i + + 2N 2 N AD A D

⁺⁺

→ → 2 2 C C

33

H H

44

O O

33

+ + 2 2 H H

22

O O + + 2 2 AT A TP P + + 2 2 N N AD A DH H + + 2 2 H H

⁺⁺

I I n n w w o o r r d d s s , , t t h h e e e e q q u u a a t t i i o o n n i i s s w w r r i i t t t t e e n n a a s s : :

G G l l u u co c o s s e e + + Ad A d e e n n o o s s in i n e e di d ip p h h o o s s p p ha h at t e e + + Ph P h o o sp s p h h a a t t e e + + N N ic i co o t t i i n n am a mi i d d e e a a d d en e ni i n n e e d d i i n n u u c c l l e e o o t t i i d d e e

↓ ↓

Py P yr ru u va v at t e e + + W W a a t t er e r + + Ad A de e n n os o s i i n n e e t t ri r i p p ho h o s s p p ha h at t e e + + N N ic i co o t t i i n n am a m i i d d e e a a d d en e n i i n n e e

d d i i nu n u cl c le eo o t t i i de d e + + Hy H yd d ro r o ge g en n io i o n n s s

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Glycolysis Enzymes:

In most kinds of cells, the enzymes that catalyze glycolytic reactions are present in the extra-mitochondrial fraction of the cell in the cytosol. One common characteristic in all the enzymes involved in glycolysis is that nearly all of them require Mg

²⁺

. The following are the enzymes that catalyze different steps throughout the process of glycolysis:

1. Hexokinase

2. Phosphoglucoisomerase 3. Phosphofructokinase 4. Aldolase

5. Phosphotriose isomerase

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6. Glyceraldehyde 3-phosphate dehydrogenase 7. Phosphoglycerate kinase

8. Phosphoglycerate mutase 9. Enolase

10. Pyruvate kinase

Glycolysis Steps:

 During glycolysis, a single mole of 6-carbon glucose is broken

down into two moles of 3-carbon pyruvate by a sequence of 10

enzyme-catalyzed sequential reactions. These reactions are

grouped under 2 phases, phase I and II.

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 Stage I comprises “preparatory” reactions which are not redox reactions and do not release energy but instead lead to the production of a critical intermediate of the pathway.

 Stage I consists of the first five steps of the glycolysis process.

 Similarly, in Stage II, redox reactions occur, energy is conserved in the form of ATP, and two molecules of pyruvate are formed.

 The last five reactions of glycolysis constitute phase II.

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The ten steps of glycolysis occur in the following sequence:

Step 1- Phosphorylation of glucose:

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 In the first step of glycolysis, the glucose is initiated or primed for the subsequent steps by phosphorylation at the C

6

carbon.

 The process involves the transfer of phosphate from the ATP to glucose forming Glucose-6-phosphate in the presence of the enzyme hexokinase and glucokinase (in animals and microbes).

 This step is also accompanied by considerable loss of energy as

heat.

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Step 2- Isomerization of Glucose-6-phosphate:

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 Glucose 6-phosphate is reversibly isomerized to fructose 6-

phosphate by the enzyme

phosphohexoisomerase/phosphoglucoisomerase.

 This reaction involves a shift of the carbonyl oxygen from C1 to

C2, thus converting an aldose into a ketose.

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Step 3- Phosphorylation of fructose-6-phosphate:

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 This step is the second priming step of glycolysis, where fructose-6-phosphate is converted into fructose-1,6- bisphosphate in the presence of the enzyme phosphofructokinase.

 Like in Step 1, the phosphate is transferred from ATP while

some amount of energy is lost in the form of heat as well.

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Step 4- Cleavage of fructose 1, 6-diphosphate:

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 This step involves the unique cleavage of the C-C bond in the fructose 1, 6-bisphosphate.

 The enzyme fructose diphosphate aldolase catalyzes the cleavage of fructose 1,6-bisphosphate between C

3

and C

4

resulting in two different triose phosphates: glyceraldehyde 3-phosphate (an aldose) and dihydroxyacetone phosphate (a ketose).

 The remaining steps in glycolysis involve three-carbon units,

rather than six carbon units.

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Step 5- Isomerization of dihydroxyacetone phosphate:

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ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 1: CARBOHYDRATES

 Glyceraldehyde 3-phosphate can be readily degraded in the subsequent steps of glycolysis, but dihydroxyacetone phosphate cannot be. Thus, it is isomerized into glyceraldehyde 3-phosphate instead.

 In this step, dihydroxyacetone phosphate is isomerized into glyceraldehyde 3-phosphate in the presence of the enzyme triose phosphate isomerase.

 This reaction completes the first phase of glycolysis.

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Step 6- Oxidative Phosphorylation of Glyceraldehyde 3-

phosphate:

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 Step 6 is one of the three energy-conserving or forming steps of glycolysis.

 The glyceraldehyde 3-phosphate is converted into 1,3- bisphosphoglycerate by the enzyme glyceraldehyde 3- phosphate dehydrogenase (phosphoglyceraldehyde dehydrogenase).

 In this process, NAD

⁺

is reduced to coenzyme NADH by the H

^–

from glyceraldehydes 3-phosphate.

 Since two moles of glyceraldehyde 3-phosphate are formed

from one mole of glucose, two NADH are generated in this step.

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Step 7- Transfer of phosphate from 1, 3-

diphosphoglycerate to ADP:

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ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 1: CARBOHYDRATES

 This step is the ATP-generating step of glycolysis.

 It involves the transfer of phosphate group from the 1, 3- bisphosphoglycerate to ADP by the enzyme phosphoglycerate kinase, thus producing ATP and 3-phosphoglycerate.

 Since two moles of 1, 3-bisphosphoglycerate are formed from

one mole of glucose, two ATPs are generated in this step.

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ZOOLOGY: SEM- III, PAPER- C7T: FUNDAMENTALS OF BIOCHEMISTRY, UNIT 1: CARBOHYDRATES

Step 8- Isomerization of 3-phosphoglycerate:

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 The 3-phosphoglycerate is converted into 2-phosphoglycerate due to the shift of phosphoryl group from C3 to C2, by the enzyme phosphoglycerate mutase.

 This is a reversible isomerization reaction.

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Step 9- Dehydration 2-phosphoglycerate:

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 In this step, the 2-phosphoglycerate is dehydrated by the action of enolase (phosphopyruvate hydratase) to phosphoenolpyruvate.

 This is also an irreversible reaction where two moles of water

are lost.

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Step 10- Transfer of phosphate from

phosphoenolpyruvate:

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 This is the second energy-generating step of glycolysis.

 Phosphoenolpyruvate is converted into an enol form of pyruvate by the enzyme pyruvate kinase.

 The enol pyruvate, however, rearranges rapidly and non- enzymatically to yield the keto form of pyruvate (i.e.

ketopyruvate). The keto form predominates at pH 7.0.

 The enzyme catalyzes the transfer of a phosphoryl group from

phosphoenolpyruvate to ADP, thus forming ATP.

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Results of Glycolysis:

The overall process of glycolysis results in the following events:

1. Glucose is oxidized into pyruvate.

2. NAD

⁺

is reduced to NADH.

3. ADP is phosphorylated into ATP.

Fates of Pyruvate:

Depending on the organism and the metabolic conditions, the

pyruvate takes one of the following three essential routes:

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The above figure shows the three possible catabolic fates of the pyruvate formed in glycolysis. Pyruvate also serves as a precursor

in many anabolic reactions,

not shown here:

1. Oxidation of pyruvate:

 In aerobic organisms, the pyruvate is then moved to the mitochondria where it is oxidized into the acetyl group of acetyl-coenzyme A (acetyl Co-A).

 This process involves the release of one mole of CO

2

.

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 Later, the acetyl CoA is completely oxidized into CO

2

and H

2

O by entering the citric acid cycle.

 This pathway follows glycolysis in aerobic organisms and plants.

2. Lactic acid fermentation:

 In conditions where the oxygen is insufficient, like in the

skeletal muscle cells, the pyruvate cannot be oxidized due to

lack of oxygen.

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 Under such conditions, the pyruvate is reduced to lactate by the process of anaerobic glycolysis.

 Lactate production from glucose also occurs in other anaerobic organisms by the process of lactic acid fermentation.

3. Alcoholic Fermentation:

 In some microbes like brewer’s yeast, the pyruvate formed

from glucose is converted anaerobically into ethanol and CO

2

.

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 This is considered the most ancient form of the metabolism of glucose, as observed in conditions where the oxygen concentration is low.

Some questions related to Glycolysis:

What is aerobic glycolysis?

Aerobic glycolysis is the process of oxidation of glucose into pyruvate

followed by the oxidation of pyruvate into CO

2

and H

2

O in the presence of

a sufficient amount of oxygen.

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What is anaerobic glycolysis?

Anaerobic glycolysis is the process that takes place in the absence of enough oxygen resulting in the reduction of pyruvate into lactate and reoxidation of NADH into NAD

⁺

.

Where does glycolysis occur?

Glycolysis occurs in the extramitochondrial fraction of the cell in the cytosol.

What are the products of glycolysis?

The products of glycolysis are two moles of pyruvate, four moles of ATPs (net gain of 2 ATPs), and one mole of NADH.

How many NADH are produced by glycolysis?

Two moles of NADH are produced by glycolysis.

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How many ATPs are formed in glycolysis?

A total of four moles of ATPs are formed in glycolysis. The net gain of ATP in glycolysis is just 2 ATPs as two ATPs are utilized during the preparatory phase of glycolysis.

What are the functions of glycolysis?

The primary function of glycolysis is to produce energy in the form of ATP.

Similarly, glycolysis also produces pyruvate, which is then oxidized

further to create more ATPs.

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