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Glycolysis
• Introduction: Glucose
utilization
• Glycolysis
• Entry of glucose into
the cell
• Preparatory phase of
glycolysis
• Energy production
Glycolysis
Embden-Meyerhoff pathway
• Introduction
• Glycolysis
• Entry of glucose into
the cell
• Preparatory phase of
glycolysis
• Energy production
Glycolysis
• Ancient Pathway
• In cytoplasm
• No oxygen required
• Used for energy
production
• Production of
intermediates for
other pathways
• Found in tissues with
limited blood supply
Entry of glucose into the cell
• Transport
• hexokinase
• glucokinase in liver
• hexokinase vs
glucokinase
• forms anion to keep in
cell
Glucose Transporters
Kinetic properties of hexokinase
Preparatory phase of glycolysis
• 2 ATP
• Phosphofructokinase
(PFK-1)
• regulated
• allosterically
Aldolase
Mechanism: Aldolase
• Nucleophillic (electron
rich group attacks
electron deficient
nucleus attack on #2
carbon.
• Lysine residue forms a
Schiff base
• OH (from C) and H from
cysteine form H2O.
• Thiolate gets H+ from
substrate, release Gly
3-P
• His residue donates H+
• Hydrolysis of Schiff
base
Energy production
• 1,3 BPGA
• PEP
• 4 ATP & 2 NADH
• Pyruvate end product
Phosphoglycerate Kinase
Effect of aresenate
Mechanism: dehydrogenase
• Ionized cysteine attacks
C-1, forming
thiohemiacetal
(aldehyde/thio group)
• Hydride ion (H-) reduces
NAD+, forms thioacyl
intermediate
• Phosphate enters
displaces thioacyl
• 1,3 Bisphsopho
disassociates.
PEP to Pyruvate
Biological Systems
• Net 2 ATP
• 2 NADH
• Most reactions at
equilibrium can be
reversed
Overall reactions of glycolysis
Regulation of Glycolysis
• ATP/AMP ratios are
important
• Two roles: energy
production and
building blocks for
biosynthesis
Regulation of Hexokinase
Phosphofructokinase: Highly
regulated
• Allosteric enzyme:
• Activated by ADP and
AMP
• Inhibited by ATP and
Citrate (from TCA
cycle)
• Fructose 2,6
bisphosphate
regulation
PFK-2
• Tandem enzyme: PFK-
2, both kinase and
phsophotase together
• Fru 2,6 P potent
activator of PFK-1
• prevents inhibition of
citrate/ATP for fatty
acid biosynthesis
• Relative velocity curves
for PFK-1
• Effect of glucagon on
PFK-1
Activation of PFK-1 by Fru 2,6 Bis
Other sites of Regulation
• Pyruvate kinase
• allosteric
• stimulated by fructose
1,6P
• inhibited by acetyl-CoA,
fatty acids
• protein kinase inhibits
pyruvate kinase
• Glyceraldehyde 3-P
dehydrogenase
• stimulated by NAD+

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450Glycolysis (1).PDF