GLYCOLYSIS

Dr Imran Siddiqui (MBBS, MPhil)

College of Medicine
King Saud Bin Abdulaziz University for Health
Sciences
Anabolism & Catabolism
Overview of Glycolysis
 Tissue-specific glucose transporters
Name Tissue Km Properties
GLUT1 RBCs, most others Basal glucose uptake
Facilitated transport—glucose moves down concentration gradient

GLUT2 Liver, pancreatic β -cells Allows glucose equilibration

GLUT3 Brain Constant uptake

GLUT4 Muscle, Fat Insulin regulated uptake

GLUT5 Small Intestine, testis Fructose transporter

Duodenum, Kidney --- Active transporters-
Active transport—glucose moves up concentration gradient, sodium moves down
SGLT-1
SGLT-2 Kidney --- couple sodium and glucose

Tissues that require glucose transport from low to high concentration

1st Phase (Energy Investment) of Glycolysis
2nd Phase (Pay off) of Glycolysis
 Phosphorylation of Glucose
• Phosphorylated glucose is impermeable
• So, it is trapped inside the cell
• The reaction is irreversible
• Catalyzed by hexokinase or glucokinase
Hexokinase:
- found in most tissues.
Glucokinase:
- Found in hepatocytes and islets cells of pancrease
 Regulation of glycolysis
• Glycolytic flux is controlled by need for ATP and/or for
intermediates formed by the pathway (e.g., for fatty acid
synthesis).
• Control occurs at sites of irreversible reactions
• Phosphofructokinase- major control point; first
enzyme “unique” to glycolysis
• Hexokinase or glucokinase
• Pyruvate kinase
•Phosphofructokinase responds to changes in:
• Energy state of the cell (high ATP levels inhibit)
• H+ concentration (high lactate levels inhibit)
• Availability of alternate fuels such as fatty acids,
ketone bodies (high citrate levels inhibit)
• Insulin/glucagon ratio in blood (high fructose 2,6-
bisphosphate levels activate)
Control points in glycolysis

Glucose-6-P - hexokinase

*
 Phosphofructokinase (PFK-1) as a
regulator of glycolysis

PFK-1 activated by:

Fructose-2,6-bisphosphate (F-2,6-P2)

PFK-2
F-6-P F-2,6-P2
PFK-1 + F-2,6-P2
F-1,6-P2
Activates PFK-1 by increasing its
affinity for fructose-6-phosphate
glycolysis and diminishing the inhibitory
effect of ATP.
 Glycolysis
Glucose

10 steps 3 regulated steps

No O2
Pyruvate Lactate

Energy (ATP) and metabolites

 Pathway Overview
• What does glycolysis do for us?
Glc
Glycogen HK (reg)
•Input to Glycogen, PPP PPP G6P •Process Glc (Frc) monomers

F6P PFK-1 (reg)

F16BP
DHAP + G3P •Form 3-C metabolites
NADH G3P DH
1,3-BPG
ATP PGK

•Generate ATP and NADH

3-PG
2-PG
PEP
PK (reg)
ATP
LDH Pyr TCA
•Regenerate NAD+
•Input to TCA cycle
Lactate
 Animated Review
Animated Review of Glycolysis