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CARBOHYDRATE:
- Most abundant organic molecule on earth.
- Carbohydrates are defined as aldehyde or keto derivatives of polyhydric alcohols.
- For example: Glycerol on oxidation is converted to D-glyceraldehyde, which is a carbohydrate derived from the trihydric alcohol (glycerol).
- All carbohydrates have the general formula CnH2nOn [or it can be re-written as Cn(H2O)n ] .
CLASSIFICATION OF CARBOHYDRATE
METABOLISM
ABSORPTION OF MONOSACCHARIDES
- Simple Diffusion
- According to concentration gradient.
- Fructose & pentoses.
- Facilitated Transport
FATE OF ABSORBED SUGARS
- Absorbed Fructose and galactose >> liver >> glucose >> uptake by tissues
PATHWAYS FOR GLUCOSE UTILIZATION
- Oxidation for production of energy
- Provides other compounds:
- Carbohydrates: i.e. fructose, galactose & pentoses.
- Glycerol 3-phosphate: triacylglycerol and phospholipids
- Acetyl CoA: cholesterol and fatty acids
- Non essential amino acids.
- Storage: glycogen in liver & triacylglycerol in adipose tissue.
- Excretion in urine.
I- The Major Pathways: for energy production.
A) Glycolysis: produces pyruvate under aerobic condition lactate under anaerobic condition.II- The Minor Pathways: for synthesis of other derivatives.
B) Krebs’ cycle: under aerobic condition, pyruvate is converted to active acetyl coA for oxidation through Krebs’ cycle.
A) Hexose monophosphate pathway (HMP): For production of pentoses and NADPH.
B) Uronic acid pathway: For production of uronic acids.
GLYCOLYSIS
- Oxidation of glucose to pyruvate in presence of O2 or lactate in absence of O2.
- Site: cytosol of all cells.
- Steps:
- Phase I (Energy utilization phase): Glucose is cleaved to two molecules of glyceraldehyde 3-phosphate. This phase consumes 2 molecules of ATP.
- Phase II (Energy recovery phase): The two molecules of glyceraldehyde 3-phosphate are converted to pyruvate under aerobic state with generation of 10 ATPs. Or lactate under anaerobic state with generation of 4 ATPs.
- All reactions are reversible except GK, PFK, PK.
|
Hexokinase |
Glucokinase |
Site |
Extrahepatic |
Liver & pancreatic β cells |
Km |
Low (high affinity) |
High (low affinity) |
G6P |
Allosteric inhibitor |
No effect |
Glucagon |
No effect |
Inhibitor |
Insulin |
No effect |
Stimulator |
IMPORTANCE OF GLYCOLYSIS
I. Energy production|
Reaction catalyzed by |
Aerobic state |
Anaerobic state |
| Hexokinase or Glucokinase |
-1 |
-1 |
| Phosphofructokinase-1 |
-1 |
-1 |
| Glyceraldehyde 3- phosphate dehydrogenase |
+6 |
0 |
| Phosphoglycerate kinase |
+2 |
+2 |
| Pyruvate kinase |
+2 |
+2 |
|
Net energy gain |
8 ATP |
2 ATP |
II Importance of Intermediates
- Pyruvate: active acetyl coA, oxaloacetate, and lactate.
- DHAP >> glycerol 3-phosphate which is used in triacylglycerol and phospholipid synthesis.
- Non essential aa :
Pyruvate >> alanine
3Phosphoglycerate >> serine.
REGULATION
Key enzymes: GK, PFK, PKStimulated by: insulin, AMP, F6P
Inhibited by: glucagon, ATP, citrate
ENERGY YIELD FROM GLUCOSE OXIDATION
Pathway |
Products |
ATP |
Glycolysis |
2 X pyruvate |
8 |
Oxidative decarboxylation of pyruvate |
2 X Acetyl CoA |
2 x 3 = 6 |
TCA, ETC |
|
2 x 12 = 24 |
Net energy gain |
|
38 |
Hexose Monophosphate Pathway (HMP)
Alternative route for glucose oxidation not for energy production.- Site: cytosol of liver, adipose tissue, ovaries, testes, RBCs & retina.
- Steps:
Oxidative irreversible phase: Glucose 6-phosphate undergoes dehydrogenation & decarboxylation to yield ribulose 5-phosphate.
Nonoxidative reversible phase: 6 molecules of ribulose 5-P are converted to 5 molecules of glucose 6-P by two enzymes: transketolase & transaldolase
IMPORTANCE OF HMP PATHWAYI- It provides ribose 5-phosphate required for synthesis of nucleotides and nucleic acids.
II- Main source of NADPH, required for:
A) Reductases
Glutathione reductase
2. Folate, retinal reducatase
3. Reducatases of FA, steroid synthesis.
B) Hydroxylases
e.g. Steroids hydroxylase
C) NADPH Oxidase: phagocytosis (respiratory burst).
URONIC ACID PATHWAY
is an alternative route for glucose oxidation.- Site: cytosol of liver
IMPORTANCE OF URONIC ACID PATHWAY:
- Main function is formation of UDP-glucuronate:
- Glycosaminoglycans (GAGs) synthesis.
- Synthesis of L-ascorbic acid (not in human) Conjugation reactions: with bilirubin, steroids to make them: more soluble, easily excreted i.e. Detoxication.
GLUCONEOGENESIS
It is the synthesis of glucose from non- carbohydrate sources.- Site: Liver, kidney.
- Steps: reversal of glycolysis, the irreversible reactions are reversed by 4 enzymes:
Sources:
- Lactate.
- Pyruvate.
- Glucogenic aa
- Glycerol
- Odd chain FA
Insulin: ↓ gluconeogenesis, ↑ glycolysis
Anti-insulin: ↑ gluconeogenesis, ↓ glycolysis
Importance:
- Source of blood glucose during fasting & starvation.
- Removal of waste products e.g. lactate, glycerol.
Glycogen Metabolism
GLYCOGENESIS
Definition: synthesis of glycogen from glucose.Site: cytosol of liver & muscles.
Steps:
GLYCOGENOLYSIS
Definition: breakdown of glycogen to glucose in liver or G6P in muscles ( due to absence of G6 phosphatase in muscles).Importance:
- In muscles: source of energy during exercise.
- In liver: source of blood glucose during 18 hours starvation.
Steps:
MCQs
1) Which of the following metabolite negatively regulates pyruvate kinase?
a) Fructose-1,6-Bisphosphate
b) Citrate
c) Acetyl CoA
d) Alanine
Ans: B
2. Gluconeogenesis occurs in the liver and kidneys. Which is of the following enzyme are important for gluconeogenesis are expressed exclusively in these tissues?
a) Glucose-6-phosphatase
b) Fructose-1,6-Bisphosphatase
c) Phosphoenolpyruvate carboxykinase
d) Pyruvate carboxylase
Ans. A
