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CARBOHYDRATE
METABOLISM
By Dr Sohil Takodara
Carbohydrate Pathways
• Glycolysis
• Hexose monophosphate(HMP) shunt
• Glycogenesis
• Glycogenolysis
• Gluconeogenesis
• Uronic acid pathway
• Glycolysis is the main pathway for oxidation of
glucose
• The end product of glycolysis is pyruvate or lactate
• Hexose monophosphate shunt is another pathway
for oxidation of glucose
• Pentoses are formed as intermediates in this
pathway
• Glycogenesis is the pathway by which glucose is
converted into glycogen for storage
• Glycogenolysis is the pathway by which stored
glycogen is broken down
• Gluconeogenesis is the pathway for synthesis of
glucose from non-carbohydrates
• Glucuronic acid is synthesised from glucose by
uronic acid pathway
Glycolysis
• Major pathway of Glucose oxidation
• “Oxidation of one molecule of glucose(6C)
produces two molecules of pyruvate(3C)
or lactate(3C)”
• Site - All the metabolic organs
• Subcellular site - Cytosol
• Only pathway that operates in anaerobic
conditions
• Also known as Embden-Meyerhof pathway
• In aerobic conditions i.e. when the supply
of oxygen is adequate, the end product of
glycolysis is PYRUVATE
• In anaerobic conditions i.e. when the
supply of oxygen is inadequate, the end
product of glycolysis is LACTATE
• The glycolytic reactions may be divided into
three phases:
1. Priming or preparatory phase
2. Splitting phase
3. Oxidative phase
Preparatory phase
STEP-1
Preparatory Phase
STEP-2
Preparatory Phase
STEP-3
Preparatory /Splitting Phase(step-4)
STEP-4
STEP-5
Oxidative/Payoff Phase
STEP-6
Oxidative Phase
STEP-7
Oxidative Phase
STEP-8
Oxidative Phase
STEP-9
Oxidative Phase STEP-10
Glycolysis-Aerobic
Glycolysis -Anaerobic
Anaerobic Glycolysis
Anaerobic glycolysis occurs in muscles during
exercise when oxygen utilisation outstrips the supply
 It also occurs in cells lacking mitochondria e.g.
erythrocytes, corneal cells and lens cells
 When the conditions become aerobic again, lactate is
converted into pyruvate again, and can be oxidised
through citric acid cycle
ATP PRODUCTION No. of ATP
Glyceraldehyde 3-
phosphate
dehydrogenase
2.5
Bisphospho
Glycerate Kinase
1
Pyruvate Kinase 1
Total 4.5
ATP CONSUMPTION No. Of ATP
Hexokinase 1
Phosphofructokinase 1
Total 2
1 Glucose=2 Pyruvate (2*4.5=9 ATP)
ATP IN AEROBIC GLYCOLYSIS
NET ATP = 9 – 2 = 7 ATP
ATP PRODUCTION No. of ATP
NO NADH NO ATP
Bisphospho
Glycerate Kinase
1
Pyruvate Kinase 1
Total 2
ATP CONSUMPTION No. Of ATP
Hexokinase 1
Phosphofructokinase 1
Total 2
1 Glucose=2 Pyruvate (2*2=4 ATP)
ATP IN ANEROBIC GLYCOLYSIS
NET ATP = 4 – 2 = 2 ATP
RAPAPORT-LEUBERING SHUNT
• 2,3 BPG Shunt
• Disperse the energy
• Delivers Oxygen to
peripheral tissues.
• Extra ATPs may inhibit
PFK
Glycolysis Inhibitors
FLUORIDE ARSENATE (partial)
Glucose
Pyruvate
Acetyl CoA
TCA cycle
ATP
Acetyl Co A + Oxaloacetate
=Citrate
Substrate
Feedback/Feed
forward
inhibition/stimulation
Allosteric regulation
Covalent
Phosphorylation
Dephosphorylation
Regulation of Glycolysis
• Two types controls for metabolic reactions:
• a) Substrate limited(Allosteric) : When
concentrations of reactant and products in the cell
are near equilibrium, then it is the availability of
substrate which decides the rate of reaction.
• b) Enzyme-limited ( Hormonal): When concentration
of substrate and products are far away from the
equilibrium, then it is activity of enzyme that decides
the rate of reaction. These reactions are the one
which control the flux of the overall pathway.
• There are three steps in glycolysis that have
enzymes which regulate the flux of
glycolysis.
I. The hexokinase (HK)/Glucokinase(GK)
II. The phoshofructokinase (PFK)
III.The pyruvate kinase
Property Hexokinase Glucokinase
Distribution All tissues Liver,Pancreas
Affinity for glucose High with low Km Low with high Km
Specificity Acts on Glu,Fru,Mannose
etc.
Acts only on glucose
Induction Non inducible Induced by Insulin
Function Acts at low blood glucose
levels
Acts only when glucose
levels is high as after meals
Inhibition Inhibited by product, i.e.
Glucose-6(P)
Not inhibited
Hexokinase
Glucose -6-P
Glucokinase
High Carbs
diet
Insulin
GlucagonStarvation
Diabetes
PFK-1
Insulin
Carbs
intake
Fructose
2,6
bisphosp
hate
Glucagon
Starvation
/Diabetes
Citrate,
ATP
Fructose 2,6 Bisphosphate
Pyruvate
Kinase
Insulin
Carbs
intake
Fructose
1,6
bisphosp
hate
Glucagon
Starvation
/Diabetes
Citrate,
ATP
Disorders
Haemolytic Anaemia
• Due to pyruvate kinase
deficiency
• Defective Glycolysis
• Destruction of RBCs
Lactic Acidosis
• Results from increased
lactate production and
decreased utilisation.
• Precipitated by
anoxia(Shock,Convulsion,
Respiratory failure,alcohol
ingestion)
• High lactate,low pH, low
bicarbonate
Significance
• Principal route for Glucose metabolism for ATP
production
• Allows tissues to survive anoxic episodes
• Provides Pyruvate, Glycerol 3-P, 2,3 BPG
• Provides intermediates for Fructose and
Galactose metabolism

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glycolysis