,CARBOHYDRATE METABOLISM
Advanced Detailed Notes (MSc Level)
PART 1: METABOLIC REGULATION
Carbohydrate metabolism is regulated at:
1. Allosteric level
2. Covalent modification (phosphorylation/dephosphorylation)
3. Hormonal level (Insulin, Glucagon, Epinephrine)
4. Substrate availability
5. Energy charge of the cell (ATP/ADP ratio)
I. GLYCOLYSIS – DETAILED REGULATION
Location: Cytoplasm
Function: Oxidation of glucose → pyruvate
Net yield: 2 ATP + 2 NADH
A. Key Irreversible Steps (Control Points)
STEP 1:
Glucose
↓ (Hexokinase / Glucokinase)
Glucose-6-phosphate
STEP 3 (Rate Limiting):
Fructose-6-phosphate
↓ (PFK-1)
Fructose-1,6-bisphosphate
STEP 10:
PEP
↓ (Pyruvate kinase)
Pyruvate
, B. Regulation in Detail
1️. Hexokinase vs Glucokinase
Feature Hexokinase Glucokinase
Location All tissues Liver & pancreas
Km Low (high affinity) High
Inhibited by G6P Not inhibited
Role Basal glucose use Post-meal glucose control
👉 Liver acts as glucose buffer.
2️. PFK-1 (MOST IMPORTANT)
This enzyme determines whether glucose enters energy production.
Activated by:
• AMP (low energy)
• ADP
• Fructose-2,6-bisphosphate
Inhibited by:
• ATP (high energy)
• Citrate (TCA intermediate)
• Low pH
3️⃣Role of Fructose-2,6-bisphosphate
This molecule connects glycolysis & gluconeogenesis.
Insulin → activates PFK-2 → ↑ F-2,6-BP → ↑ Glycolysis
Glucagon → activates FBPase-2 → ↓ F-2,6-BP → ↑ Gluconeogenesis
This is reciprocal regulation.
C. Hormonal Regulation
FED STATE (High Insulin)
• ↑ Glucokinase
• ↑ PFK-1
• ↑ Pyruvate kinase
Advanced Detailed Notes (MSc Level)
PART 1: METABOLIC REGULATION
Carbohydrate metabolism is regulated at:
1. Allosteric level
2. Covalent modification (phosphorylation/dephosphorylation)
3. Hormonal level (Insulin, Glucagon, Epinephrine)
4. Substrate availability
5. Energy charge of the cell (ATP/ADP ratio)
I. GLYCOLYSIS – DETAILED REGULATION
Location: Cytoplasm
Function: Oxidation of glucose → pyruvate
Net yield: 2 ATP + 2 NADH
A. Key Irreversible Steps (Control Points)
STEP 1:
Glucose
↓ (Hexokinase / Glucokinase)
Glucose-6-phosphate
STEP 3 (Rate Limiting):
Fructose-6-phosphate
↓ (PFK-1)
Fructose-1,6-bisphosphate
STEP 10:
PEP
↓ (Pyruvate kinase)
Pyruvate
, B. Regulation in Detail
1️. Hexokinase vs Glucokinase
Feature Hexokinase Glucokinase
Location All tissues Liver & pancreas
Km Low (high affinity) High
Inhibited by G6P Not inhibited
Role Basal glucose use Post-meal glucose control
👉 Liver acts as glucose buffer.
2️. PFK-1 (MOST IMPORTANT)
This enzyme determines whether glucose enters energy production.
Activated by:
• AMP (low energy)
• ADP
• Fructose-2,6-bisphosphate
Inhibited by:
• ATP (high energy)
• Citrate (TCA intermediate)
• Low pH
3️⃣Role of Fructose-2,6-bisphosphate
This molecule connects glycolysis & gluconeogenesis.
Insulin → activates PFK-2 → ↑ F-2,6-BP → ↑ Glycolysis
Glucagon → activates FBPase-2 → ↓ F-2,6-BP → ↑ Gluconeogenesis
This is reciprocal regulation.
C. Hormonal Regulation
FED STATE (High Insulin)
• ↑ Glucokinase
• ↑ PFK-1
• ↑ Pyruvate kinase
