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BIOCHEMISTRY- III
CATABOLIC PATHWAYS OF
CARBOHYDRATES - GLYCOLYSIS
7/13/2017
Biosynthetic pathways
1. Biosynthesis of Carbohydrates
2. Biosynthesis of Lipids
Biosynthesis of Fatty acids
Biosynthesis of Membrane Lipids
3. Biosynthesis of Amino acids
7/13/2017
Glycolysis takes place in the Cytosol of cells.
Glucose enters the Glycolysis pathway by conversion to glucose-6-
phosphate.
Initially there is energy input corresponding to cleavage of two ~P
bonds of ATP.
H O
OH
H
OHH
OH
CH2OPO3
2
H
OH
H
1
6
5
4
3 2
glucose-6-phosphate
7/13/2017
Glycolysis
Glucose is converted to two molecules of pyruvate.
An anaerobic reaction in cytoplasm.
10 Reactions
7/13/2017
A. Energy investment phase or Preparative or priming
stage
B. Splitting phase
C. Energy generation phase or Pay-off phase
7/13/2017
Glycolysis
Steps [1] – [3] and [4] energy investment phase and splitting phase:
The 6-carbon glucose molecule is converted into two 3-carbon segments.
2 ATP molecules are hydrolyzed.
7/13/2017
Glycolysis
Steps ]- [5] and [6] – [10] Splitting and energy-generating phase:
producing 1 NADH and 2 ATPs for each pyruvate formed.
7/13/2017
Glycolysis
Enzymes:
7/13/2017
Step [1] begins with the
phosphorylation of glucose
into glucose 6-phosphate,
using an ATP and a kinase
enzyme.
Glycolysis
7/13/2017
Step [2] isomerizes
glucose 6-phosphate to
fructose 6-phosphate
with an isomerase enzyme.
Glycolysis
7/13/2017
Step [3] is the
phosphorylation of
fructose 6-phosphate into
fructose 1,6-bisphosphate
with a kinase enzyme.
Glycolysis
7/13/2017
Glycolysis
Overall, the first three steps of glycolysis:
1. 2 phosphate groups is added.
2. A 6-membered glucose ring is isomerized
into a 5-membered fructose ring.
3. The energy stored in 2 ATP molecules is utilized to
modify the structure of glucose
7/13/2017
Glycolysis- Splitting phase
Step [4] cleaves the fructose ring into a dihydroxy-acetone phosphate
and a glyceraldehyde 3-phosphate.
7/13/2017
Step [5] isomerizes the dihydroxyacetone phosphate
into another glyceraldehyde 3-phosphate.
Glycolysis
Thus, the first phase of glycolysis converts glucose into
2 glyceraldehyde 3-phosphate units and 2 ATP is used.
7/13/2017
In step [6] the aldehyde end of the molecule is oxidized and
phosphorylated by a dehydrogenase enzyme and NAD+;
this produces 1,3-bisphospho-glycerate and NADH.
Glycolysis- Energy Generating Phase
7/13/2017
Glycolysis
In step [7], the phosphate group is transferred onto an ADP with a
kinase enzyme, forming 3-phosphoglycerate and ATP.
7/13/2017
In step [8], the phosphate group is isomerized to
a new position in 2-phosphoglycerate.
Glycolysis
7/13/2017
In step [9], water is lost to form phosphoenol-pyruvate.
Glycolysis
7/13/2017
Glycolysis
In step [10], the phosphate is transferred to an ADP,
yielding pyruvate and ATP with a kinase enzyme.
7/13/2017
Pyruvate
The 2 glyceraldehydes 3-phosphate units are converted into 2
pyruvate units in phase two of glycolysis.
Overall, the energy-generating phase forms 2 NADHs and 4
ATPs.
Glycolysis
7/13/2017
Glycolysis
Overall of glycolysis
2 ATPs are used in phase one of glycolysis, and 4 ATPs are made in
phase two of glycolysis.
The net result is the synthesis of 2 ATPs from glycolysis.
The 2 NADHs formed are made in the cytoplasm and must be
transported to the mitochondria to join the electron transport chain
and make ATP.
7/13/2017
under aerobic
conditions
under anaerobic
conditions
in fermentation
by microorganisms
The fate of pyruvate
7/13/2017
Aerobic conditions
The NADH formed needs O2 to return to NAD+, so without O2 no additional
pyruvate can be oxidized.
Pyruvate must diffuse across the outer and inner membrane of mitochondria
into the matrix.
7/13/2017
Fermentation is the anaerobic conversion of glucose to ethanol and
CO2 by yeast and other microorganisms.
Fermentation
7/13/2017
REGULATION OF GLYCOLYSIS
 The three enzymes namely hexokinase (and glucokinase), phosphofructokinase and
pyruvate kinase, catalysing the irreversible reactions regulate glycolysis.
 Hexokinase is inhibited by glucose 6-phosphate. This enzyme prevents the
accumulation of glucose 6-phosphate due to product inhibition.
7/13/2017
Glucose 6-phosphate
PHOSPHOFRUCLOKINASE (PFK)
 Phosphofruclokinase (PFK) is the most
important regulatory enzyme in glycolysis.
 This enzyme catalyses the rate limiting
committed step.
 PFK is an allosteric enzyme regulated by
allosteric effectors ATP, citrate and H+ ions
(low pH) are the most important allosteric
inhibitors.
 Whereas, fructose2 ,6-bisphosphate, ADP,
AMP and Pi are the allosteric activators.
7/13/2017
ROLE OF FRUCTOSE 2, 6-BISPHOSPHATE
IN GLYCOLYSIS
7/13/2017
REGULATION OF PYRUVATE KINASE
7/13/2017
Inhibited by ATP and activated by F1,6-B

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Glycoysis sem iii

  • 1. BIOCHEMISTRY- III CATABOLIC PATHWAYS OF CARBOHYDRATES - GLYCOLYSIS 7/13/2017
  • 2. Biosynthetic pathways 1. Biosynthesis of Carbohydrates 2. Biosynthesis of Lipids Biosynthesis of Fatty acids Biosynthesis of Membrane Lipids 3. Biosynthesis of Amino acids 7/13/2017
  • 3. Glycolysis takes place in the Cytosol of cells. Glucose enters the Glycolysis pathway by conversion to glucose-6- phosphate. Initially there is energy input corresponding to cleavage of two ~P bonds of ATP. H O OH H OHH OH CH2OPO3 2 H OH H 1 6 5 4 3 2 glucose-6-phosphate 7/13/2017
  • 4.
  • 5. Glycolysis Glucose is converted to two molecules of pyruvate. An anaerobic reaction in cytoplasm. 10 Reactions 7/13/2017
  • 6. A. Energy investment phase or Preparative or priming stage B. Splitting phase C. Energy generation phase or Pay-off phase 7/13/2017
  • 7. Glycolysis Steps [1] – [3] and [4] energy investment phase and splitting phase: The 6-carbon glucose molecule is converted into two 3-carbon segments. 2 ATP molecules are hydrolyzed. 7/13/2017
  • 8. Glycolysis Steps ]- [5] and [6] – [10] Splitting and energy-generating phase: producing 1 NADH and 2 ATPs for each pyruvate formed. 7/13/2017
  • 10. Step [1] begins with the phosphorylation of glucose into glucose 6-phosphate, using an ATP and a kinase enzyme. Glycolysis 7/13/2017
  • 11. Step [2] isomerizes glucose 6-phosphate to fructose 6-phosphate with an isomerase enzyme. Glycolysis 7/13/2017
  • 12. Step [3] is the phosphorylation of fructose 6-phosphate into fructose 1,6-bisphosphate with a kinase enzyme. Glycolysis 7/13/2017
  • 13. Glycolysis Overall, the first three steps of glycolysis: 1. 2 phosphate groups is added. 2. A 6-membered glucose ring is isomerized into a 5-membered fructose ring. 3. The energy stored in 2 ATP molecules is utilized to modify the structure of glucose 7/13/2017
  • 14. Glycolysis- Splitting phase Step [4] cleaves the fructose ring into a dihydroxy-acetone phosphate and a glyceraldehyde 3-phosphate. 7/13/2017
  • 15. Step [5] isomerizes the dihydroxyacetone phosphate into another glyceraldehyde 3-phosphate. Glycolysis Thus, the first phase of glycolysis converts glucose into 2 glyceraldehyde 3-phosphate units and 2 ATP is used. 7/13/2017
  • 16. In step [6] the aldehyde end of the molecule is oxidized and phosphorylated by a dehydrogenase enzyme and NAD+; this produces 1,3-bisphospho-glycerate and NADH. Glycolysis- Energy Generating Phase 7/13/2017
  • 17. Glycolysis In step [7], the phosphate group is transferred onto an ADP with a kinase enzyme, forming 3-phosphoglycerate and ATP. 7/13/2017
  • 18. In step [8], the phosphate group is isomerized to a new position in 2-phosphoglycerate. Glycolysis 7/13/2017
  • 19. In step [9], water is lost to form phosphoenol-pyruvate. Glycolysis 7/13/2017
  • 20. Glycolysis In step [10], the phosphate is transferred to an ADP, yielding pyruvate and ATP with a kinase enzyme. 7/13/2017 Pyruvate
  • 21. The 2 glyceraldehydes 3-phosphate units are converted into 2 pyruvate units in phase two of glycolysis. Overall, the energy-generating phase forms 2 NADHs and 4 ATPs. Glycolysis 7/13/2017
  • 22. Glycolysis Overall of glycolysis 2 ATPs are used in phase one of glycolysis, and 4 ATPs are made in phase two of glycolysis. The net result is the synthesis of 2 ATPs from glycolysis. The 2 NADHs formed are made in the cytoplasm and must be transported to the mitochondria to join the electron transport chain and make ATP. 7/13/2017
  • 23. under aerobic conditions under anaerobic conditions in fermentation by microorganisms The fate of pyruvate 7/13/2017
  • 24. Aerobic conditions The NADH formed needs O2 to return to NAD+, so without O2 no additional pyruvate can be oxidized. Pyruvate must diffuse across the outer and inner membrane of mitochondria into the matrix. 7/13/2017
  • 25. Fermentation is the anaerobic conversion of glucose to ethanol and CO2 by yeast and other microorganisms. Fermentation 7/13/2017
  • 26. REGULATION OF GLYCOLYSIS  The three enzymes namely hexokinase (and glucokinase), phosphofructokinase and pyruvate kinase, catalysing the irreversible reactions regulate glycolysis.  Hexokinase is inhibited by glucose 6-phosphate. This enzyme prevents the accumulation of glucose 6-phosphate due to product inhibition. 7/13/2017 Glucose 6-phosphate
  • 27. PHOSPHOFRUCLOKINASE (PFK)  Phosphofruclokinase (PFK) is the most important regulatory enzyme in glycolysis.  This enzyme catalyses the rate limiting committed step.  PFK is an allosteric enzyme regulated by allosteric effectors ATP, citrate and H+ ions (low pH) are the most important allosteric inhibitors.  Whereas, fructose2 ,6-bisphosphate, ADP, AMP and Pi are the allosteric activators. 7/13/2017
  • 28. ROLE OF FRUCTOSE 2, 6-BISPHOSPHATE IN GLYCOLYSIS 7/13/2017
  • 29. REGULATION OF PYRUVATE KINASE 7/13/2017 Inhibited by ATP and activated by F1,6-B