FACULTY OF MEDICINE

MEDICAL BIOCHEMISTRY

GLYCOLYSIS
DR. METE ÖZKOÇ
 Glycolysis: An Overview

➢ Glycolysis, the major pathway for glucose oxidation, occurs in the cytosol
of all cells.

➢ It is unique, in that it can function either aerobically or anaerobically,

depending on the availability of oxygen and intact mitochondria.

➢ It allows tissues to survive in presence or absence of oxygen, e.g., skeletal

muscle.

➢ RBCs, which lack mitochondria, are completely reliant on glucose as their

metabolic fuel, and metabolizes it by anaerobic glycolysis.
What is glycolysis?
GLYCOLYSIS
STAGE I

STAGE II
FIRST STAGE-ENERGY INVESTMENT PHASE
FIRST REACTION: GLUCOSE → G6P

 GLUCOSE CONVERTED TO GLUCOSE-6-PO4

 ATP İS NEEDED
 CATALYZED BY HEXOKİNASE OR GLUCOKİNASE
SECOND REACTION: G6P → F6P

 PHOSPHOGLUCOISOMERASE
 ALDOSE IS CONVERTED TO KETOSE
THIRD REACTION: F6P → FBP

 RATE LIMITING ENZYME – ALLOSTERIC

 Inhibited by high ATP, citric acid, long-chain fatty acids

 Stimulated by ADP or AMP

4TH REACTION (CLEAVAGE): FBP→ DHAP + GAP

 Six carbon molecule split into 2- 3 carbon molecules

 Aldose and ketose
5TH REACTION: DHAP → GAP
STAGE (PHASE) 1 OF THE GLYCOLYSIS
SECOND STAGE- PAYOFF OR ENERGY
GENERATION PHASE
6TH REACTION: GA3P→1,3-BPG (FIRST
HIGH-ENERGY INTERMEDIATE)

 Redox reaction
 7TH REACTION: 1,3-BPG→ 3PG (FIRST
SUBSTRATE LEVEL PHOSPHORILATION)

 Formation of ATP – substrate level phosphorylation

8TH REACTION: 3PG→2PG
9TH REACTION: 2PG→PEP (SECOND
HIGH ENERGY INTERMEDIATE)
F-
10TH REACTION: PEP→PYRUVATE (SECOND
SUBSTRATE LEVEL PHOSPHORILATION)

K+
Glycolysıs
FATE OF PYRUVATE
Alcohol Fermentation
 Which organisms carry out this process?
 Yeast
 Some other microorganisms
 PDC requires thiamine pyrophosphate (TPP) as coenzyme
 NAD+ is regenerated
Lactic Acid Fermentation
 Occurs in muscle cells, RBC an in some other microorganisms
 Regenerates NAD+
Control of Glycolysis
 Hexokinase
 Phosphofructokinase
 Pyruvate kinase

 These 3 reactions of glycolysis, function with large negative free

energy changes. These enzymes operate far from equilibrium and
act like control points of glycolysis.
Hexokinase
 Hexokinase is inhibited by its product glucose-6-P
 Glucokinase, an isozyme of hexokinase, is not inhibited by glucose-6-P
 Found in liver
 Has lower affinity in glucose
Phosphofructokinase
 Most important control point in mammalian glycolytic pathway
 Allosteric enzyme
 Activated by amp and fructose 2,6 bisphosphate (F2,6-bisP)
 Inhibited by high levels of ATP, Acetyl-CoA, Citrate, Fatty Acids
PYRUVATE KINASE
REFERENCES