Glycolysis

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 2,6bisphosphate 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 PFK-1 + F-1,6-P2 glycolysis

F-2,6-P2

F-2,6-P2

Activates PFK-1 by increasing its affinity for fructose-6-phosphate and diminishing the inhibitory effect of ATP.

Glycolysis Glucose 10 steps Pyruvate

3 regulated steps No O2

Lactate

Energy (ATP) and metabolites

Pathway Overview • What does glycolysis do for us? Glc

Glycogen PPP

•Input to Glycogen, PPP

G6P F6P

HK (reg) •Process Glc (Frc) monomers

PFK-1 (reg)

F16BP NADH

DHAP +

G3P

•Form 3-C metabolites G3P DH

1,3-BPG PGK

ATP

3-PG

•Generate ATP and NADH

2-PG PEP ATP •Regenerate NAD+

LDH

Lactate

Pyr

PK (reg)

TCA •Input to TCA cycle

Animated Review Animated Review of Glycolysis