Glycolysis | Pathway of Glycolysis |

This presentation contains Short introduction on metabolism, Glycolysis & Pathway of Glycolysis.

2. Introduction to Metabolism
Metabolism: All the chemical reactions, occurring in
the living system, are collectively referred to as
metabolism.
Metabolite: Is a substrate or an intermediate or a Metabolite: Is a substrate or an intermediate or a
product in the metabolic reactions.
Metabolic pathway: It constitutes a series of
enzymatic reactions to produce specific products.

3. Metabolism
AnabolismCatabolism

4. Catabolism : The degradativeprocesses
concerned with the breakdown of complex
molecules to simpler ones, with a concomitant
release of energy.
Anabolism : The biosynthetic reactions
involving the formation of complex molecules involving the formation of complex molecules
from simple precursors.
•Amphibolism: It is the type of reactions which
are both
catabolic
and
anabolic
in nature.

5. Catabolism and Anabolism: Outline

6. Catabolism
•The main purpose of catabolism is to trap the
energyof the biomoleculesin the form of ATP
and to generate the substances (precursors)
required for the synthesis of complex required for the synthesis of complex
molecules.

7. Catabolism occurs in three stages
Stage 1:Conversion of complex molecules into
their building blocks
Stage 2:Formation of simple intermediatesStage 2:Formation of simple intermediates
Stage 3: Final oxidation of acetyl CoA

8. Stage 1
Conversion of complex molecules into their
building blocks:
•Polysaccharides are broken down to •Polysaccharides are broken down to
monosaccharides,
•Lipids to free fatty acids & glycerol,
•Proteins to amino acids.

9. Stage 2
Formation of simple intermediates :
•The building blocks produced in stage 1 are
degraded to simple intermediates such as degraded to simple intermediates such as
pyruvateand acetyl CoA.
•A small quantity of energy (as ATP) is captured
in stage 2.

10. Stage 3
Final oxidation of acetyl CoA:
•Acetyl CoAis completely oxidized to CO2, liberating
NADH and FADH2 that finally get oxidized to
release large quantity of energy (as ATP). release large quantity of energy (as ATP).
•Krebs cycle (or citric acid cycle) is the common
metabolic pathway involved in the final oxidation of
all energy-rich molecules. This pathway accepts the
carboncompounds (pyruvate, succinateetc.)
derived from carbohydrates, lipids or proteins

12. Anabolism
•For the synthesis of a large variety of complex
molecules, the starting materials are relatively
few. These include pyruvate, acetyl CoAand
the intermediates of citric acid cycle. Besides the intermediates of citric acid cycle. Besides
the availability of precursors, the anabolic
reactions are dependent on the supply of
energy (as ATP or GTP) and reducing
equivalents (as NADPH + H+).

13. Types of metabolic reactions
•The biochemical reactions are mainly of four
types
Oxidation-reduction.Oxidation-reduction.
Group transfer.
Rearrangement and isomerization.
Make and break of carbon-carbon bonds.
Free radical reactions.

14. Carbohydrate MetabolismCarbohydrate Metabolism

15. Glycolysis
•In glycolysisa molecule of glucose is degraded
in a series of enzyme-catalyzed reactions to
yield two molecules of the three-carbon
compound pyruvate.compound pyruvate.
•Glycolysis(from the Greek glykys, meaning
“sweet,” and lysis, meaning “splitting”).

16. •It is also known as Embden-Meyerhof
pathway, where the oxidation of glucose to
pyruvateand lactate takes place.

17. Reactions of glycolysis
•The pathway can be divided into three distinct
phases
Energy investment phase or priming stage: Energy investment phase or priming stage:
Step 1, 2 and 3
Splitting phase: Step 4 and 5
Energy generation phase:Step 6, 7, 8, 9 & 10.
Steps are discussed later.

18. (Glycolysis) Step I
•Glucose is phosphorylatedto glucose 6-phosphate
by hexokinaseor glucokinase. This is an irreversible
reaction, dependent on ATP and Mg2+.
•Hexokinasecatalyses the phosphorylationof various •Hexokinasecatalyses the phosphorylationof various
hexoses(fructose, mannose etc.), has low Km for
substrates and is inhibited by glucose 6-phosphate.
•Glucokinasepresent in liver, catalyses the
phosphorylationof only glucose, has high Km for
glucose and is not inhibited by glucose 6-phosphate.

19. (Glycolysis) Step I -continued
•Due to low Km, glucose is utilized by hexokinase
even at low concentration, whereas glucokinase
acts only at higher levels of glucose.
•Due to High Km of Glucokinase: It phosphorylates•Due to High Km of Glucokinase: It phosphorylates
glucose only at higher concentration of glucose.
•Due to Low Km of Hexokinase:It phosphorylates
glucose even at lower concentration of glucose.

20. (Glycolysis) Step I -continued

21. (Glycolysis) Step II
•Glucose 6-phosphate undergoes isomerization
to give fructose 6-phosphate in the presence
of the enzyme phosphohexoseisomeraseand
Mg2+.Mg2+.

22. (Glycolysis) Step II -continued

23. (Glycolysis) Step III
•Fructose 6-phosphate is phosphorylatedto
fructose 1,6-bisphosphate by
phosphofructokinase(PFK). This is an
irreversible and a regulatory step in glycolysis.irreversible and a regulatory step in glycolysis.

24. (Glycolysis) Step III -continued

25. (Glycolysis) Step IV
•The six carbon fructose 1,6-bisphosphateis
split (hence the name glycolysis) to two three-
carbon compounds, glyceraldehyde3-
phosphateand dihydroxyacetonephosphate phosphateand dihydroxyacetonephosphate
by the enzyme aldolase(fructose 1,6-
bisphosphatealdolase).

26. (Glycolysis) Step IV -continued

27. (Glycolysis) Step V
•The enzyme phosphotrioseisomerase
catalyses the reversible interconversionof
glyceraldehyde3-phosphate and
dihydroxyacetonephosphate. Thus, two dihydroxyacetonephosphate. Thus, two
molecules of glyceraldehyde3-phosphate are
obtained from one molecule of glucose.

28. (Glycolysis) Step V -continued

29. (Glycolysis) Step VI
•Glyceraldehyde3-phosphate dehydrogenase
converts glyceraldehyde3-phosphate to 1,3-
bisphosphoglycerate.
•This step is important as it is involved in the
formation of NADH + H
+
and a high energy
compound 1,3-bisphosphoglycerate.

30. (Glycolysis) Step VI -continued

31. (Glycolysis) Step VII
•The enzyme phosphoglyceratekinaseacts on
1,3-bisphosphoglycerate resulting in the
synthesis of ATP and formation of 3-
phosphoglycerate. phosphoglycerate.
•Phosphoglyceratekinasereaction is reversible, a
rare example among the kinasereactions.

32. (Glycolysis) Step
VII -continued

33. (Glycolysis) Step VIII
•3-Phosphoglycerate is converted to 2-
phosphoglycerate by phosphoglycerate
mutase. This is an isomerizationreaction.

34. (Glycolysis) Step VIII -continued

35. (Glycolysis) Step IX
•The high energy compound phosphoenol
pyruvateis generated from 2-
phosphoglycerate by the enzyme enolase.
•This enzyme requires Mg2+ orMn2+ and is
inhibited by fluoride.

36. (Glycolysis) Step IX -continued

37. (Glycolysis) Step X
•The enzyme pyruvatekinasecatalyses the
transfer of high energy phosphate from
phosphoenolpyruvateto ADP, leading to the
formation of ATP.formation of ATP.
•This step also is a substrate level
phosphorylation. This reaction is irreversible.

38. (Glycolysis)
Step X -
continued

39. •In this substrate-level phosphorylation, the
product pyruvatefirst appears in its enolform,
then tautomerizesrapidly and non-enzymatically
to its ketoform, which predominates at pH 7

40. Pathway of Glycolysis:Pathway of Glycolysis:
Diagram/Pictorial Representation

41. Cont
…

42. Cont. from prev. page

44. Significance
Enzymes for glycolysisare present in the cytosomal
fraction of the cell.
Glycolysisoccurs in the absence of oxygen (anaerobic)
or in the presence of oxygen (aerobic). or in the presence of oxygen (aerobic).
Lactateis the end product under anaerobic condition.
Pyruvateis the end product under aerobic condition.
Glycolysisis a major pathway for ATP synthesis in
tissues lacking mitochondria, e.g. erythrocytes, cornea,
lens etc.

45. Glycolysisis very essential for brain which is
dependent on glucose for energy. The glucose in
brain has to undergo glycolysisbefore it is
oxidized to CO2 and H2O.
Glycolysisis a central metabolic pathway with
many of its intermediates providing branch point
to other pathways. Thus, the intermediatesof to other pathways. Thus, the intermediatesof
glycolysisare useful for the synthesis of amino
acids and fat.
Reversal of glycolysisalong with the alternate
arrangements at the irreversible steps, will result
in the synthesis of glucose (gluconeogenesis).

46. Regulation of glycolysis
•The three enzymes namely hexokinase(and
glucokinase), phosphofructokinaseand
pyruvatekinase, catalysingthe irreversible
reactions regulate glycolysis.reactions regulate glycolysis.

47. •Hexokinaseis inhibited by glucose 6-phosphate. This
enzyme prevents the accumulation of glucose 6-phosphate
due to product inhibition. Glucokinase, which specifically
phosphorylatesglucose, is an inducible enzyme. The
substrate glucose, probably through the involvement of
insulin, induces glucokinase.
•Phosphofructokinase(PFK) is the most important •Phosphofructokinase(PFK) is the most important
regulatory enzyme in glycolysis. This enzyme catalyses the
rate limiting committed step. PFK is an allostericenzyme
regulated by allostericeffectors. ATP, citrate and H+ ions
(low pH) are the most important allostericinhibitors,
whereas, fructose 2,6-bisphosphate, ADP, AMP and Pi are
the allostericactivators.

48. Energetics(Anaerobic)
•Glycolysis(anaerobic) may be summarized by
the net reaction:
Glucose + 2ADP + 2Pi 2Lactate + 2ATP
•One molecule of glucose yields two molecules of •One molecule of glucose yields two molecules of
pyruvate, it results in the net yield of two molecules of
ATP.
•As such four molecules of ATP are produced at step 6
and 9, but two ATP are consumed in step 1 and 3.
•Hence the net yield is only two ATP.

49. Energetics(Aerobic)
•In aerobic condition, two NADH molecules was
generated in step 5, which enters into
mitochondria via Electron transport chain.
Each NADH produce 3 ATPs. •Each NADH produce 3 ATPs.
•Since 2 NADH molecule are produced from one
molecule of glucose, 6 ATPs are produced.
•Thus in Aerobic condition, 8 ATPs are produced.

50. References:
•Biochemistry 4
th
Edition by Dr. U. Satyanarayana& Dr. U. Chakrapani
•Harper’s Illustrated Biochemistry, twenty-sixth edition by Robert K. Murray, Daryl K. Granner, Peter A. Mayes &
Victor W. Rodwell
•Lehninger, Principle of Biochemistry, Fourth edition by David L. Nelson and Michael M. Cox