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After Digestion And Absorption
Of Food What Next?
General Overview Of Metabolism
(Carbohydrate, Protein, Fat)
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Carbohydrate Chemistry and Metabolism
By Gladys Kaba
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1. Carbohydrate chemistry
2. Summary of digestion and absorption of carbohydrates.
3. General overview of metabolism
Outline
4. Carbohydrate Metabolism1. Glycolysis2. TCA cycle3. Gluconeogenesis
4. Metabolism of (Fructose, galactose, Mannose)
5. PPP6. Glycogenesis and Glycogenolysis
Outline
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After Digestion And Absorption
Of Carbohydrates What Next?
Carbohydrate Metabolism(Glucose)
We eat food containing carbohydrates
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General Overview Of Metabolism(Carbohydrate, Protein, Fat)
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Overview Of Carbohydrate Metabolism
(1) Glycolysis - Summary
Glucose (6C)
2 Pyruvate (3C)
2 ATP
2 ADP
4 ADP
4 ATP
2 NAD
2 NADH + H
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glycolysis occurs in the cytosol
Location Of Glycolytic Enzymes?
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Glycolysis Provides Energy
Glycolysis Provides Substrate for
OxidationIntermediates Products are used in Other Pathways
1. 2,3-bisphosphoglycerate, 2. fatty acid and cholesterol
synthesis3. Alanine, 4. glycerol 3-phosphate
Functions/Importance Of Glycolysis
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Erythrocytes (Red blood cells)
Lens and cornea of the eye
Cells in brain cells
Cells With Special Needs Of Glycolysis
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Physiological And Pathophysiological Conditions
with special need for Glycolysis
Fed State
Exercising muscles
Cancer cells-----Warburg effect
GlucoseGlucose 6-phosphate
Fructose 6-phosphate
Hexokinase
Phosphohexoseisomerase
Phosphofructokinase-1
Fructose 1,6-bisphosphate
1,3-Bisphosphoglycerate
Glyceraldehyde 3-phosphate dehydrogenase
Phosphoglycerate kinase
3-Phosphoglycerate
2-Phosphoglycerate
Phosphoglyceratemutase
Pyruvatekinase Pyruva
te
Phosphoenolpyruvate
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Glycolysis Regulation
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Abnormalities Associated with Glycolytic pathway
Affected Glycolytic enzyme/reaction
Genetic Deficiencies of Glycolysis
• pyruvate kinase• phosphoglycerate
kinase
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Mercury Arsenic
Toxin affecting Glycolytic pathway
After Glycolysis What next after?
Glucose → 2 Pyruvate
Lactate (anaerobic)
Acetyl-CoA (TCA cycle)
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1. Conversion of pyruvate to Acetyl CoAaerobic conditions
CH3
O
O
O
pyruvate
CO2HSCoA
CH3 SCoA
O
acetyl CoA
NADHNAD+
pyruvate dehydrogenase complex
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Location Of Pyruvate Dehydrogenase ?
Glucose
Pyruvic acid
Acetyl-CoA
CitricAcidCycle
Electron Transport
ATP Production
mitochondrion
cytoplasm Glycolysis
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Kreb’s Cycle
Carbohydrate, protein, and Fat Metabolism
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Kreb’s Cycle
Aka Tricarboxylic Acid Cycle TCA Cycle Citric Acid Cycle
Location Of Pyruvate DehydrogenaseAnd The TCA-cycle Enzymes?22
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Main Function of the Kreb’s cycle
• Oxidative process– 3 NADH– FADH2
– GTP• X 2 per glucose
– 6 NADH– 2 FADH2
– 2 GTP• All ultimately turned into ATP (oxidative
phosphorylation/ electron transport chain)
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CH3 C
O
SCoAacetyl CoA
C O
CH2C
O
COO
O
oxaloacetate
CoASH
citrate synthase
COO
CH2CCH2
C
OH C O
O
O Ocitrate
aconitase
COO
CHCHCH2C
C O
O
OO
OH
isocitrate
NADNADH
CO2
COO
CCH2CH2
COO
O
isocitrate dehydrogenase
alpha ketoglutarate
NADNADH
CoASHCO2
CCH2
CH2C
OO
OSCoA
succinyl CoA
alpha ketoglutaratedehydrogenase
GDP
GTPCoASH
CC
CC
OO
O O
H
H
succinate
succinyl CoAsynthetase
FAD
FADH2succinatedehydrogenase
CCH2
CH2
COO
O O
fumarate
OH2
CCH
CH2
COO
O O
OH
malatefumarase
NADNADH
malatedehydrogenase
Kreb's Cycle
OH2+
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Total Energy per glucose
A) Cytosol– Glycolysis
• 2 NADH• 2 ATP
B) Mitochondrion– Pyruvate dehydrogenase
• 2 NADH --Krebs
• 6 NADH• 2 FADH2
• 2 GTP 27
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Abnormalities / Diseases Associated With PDH And The
TCA Cycle1)Genetic Deficiency of Pyruvate
Dehydrogenase
2) Genetic Diseases of the TCA Cycle :
Fumarase deficiency Succinate dehydrogenase α-ketoglutarate dehydrogenase
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3) Thiamine Deficiency -- classical beriberi,
Pyuvate Dehydrogenase α-ketoglutarate Dehydrogenase
Abnormalities / Diseases Associated With PDH And The
TCA Cycle
Regulation of the Tricarboxylic Acid Cycle?
About half page to be submitted next Wednesday before The class.
Students Review Question?
Additional questions would be sent through the email on Thursday.
After Glycolysis What next after?
Glucose → 2 Pyruvate
Lactate (anaerobic)
Acetyl-CoA (TCA cycle)
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COO–
C O
CH3
COO–
HC OH
CH3
LactatePyruvate
Lactate dehydrogenase
NADH + H+ NAD+
(oxidized) (reduced)
2. Conversion To Lactate (Anaerobic conditions)
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Lactate can be transported by blood to liver and used in gluconeogenesis
Cori cycle
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Exercising muscles and the Cori Cycle
How do cytosolic/cytoplasmic NADH get into the
mitochondrial?
1. glycerol 3-phosphateshuttle - NADH as FADH
2. malate-aspartate shuttle- NADH as NADH
How do cytosolic/cytoplasmic NADH get into the
mitochondrial?
37The malate-aspartate shuttle.
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Overview Of Carbohydrate Metabolism
Gluconeogenesisnon-carbohydrate precursors are
converted to glucose.
Tissues In Which Gluconeogenesis Is Active
1) liver
2) Renal Cortex
1) Maintaining the blood glucose in the fasted state
2) But the brain, red blood cells, and renal medulla, rely on glycolysis for ATP.
Functions and importance Gluconeogenesis
Physiological Conditions In Which
Gluconeogenesis Is Especially Active fasted state,
when stored as glycogen is depleted
plasma concentration of glucose decline
Physiological Conditions In Which
Gluconeogenesis Is Especially Active During prolonged physical
exercise.
important in the neonate. (the first few hours after delivery).
Gluconeogenesis
starting material
lactate,
pyruvate,
Oxaloacetate
glycerol
Some amino acids
propionic acid ( oxidation of odd-chain fatty acids and branched methyl fatty acids)
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Biochemical Reactions Of Gluconeogenesis
1.Most are the same as glycolysis,
2.But in the opposite direction,
3.With some few exceptions
GlucoseGlucose 6-phosphate
Fructose 6-phosphate
Hexokinase
Phosphohexoseisomerase
Phosphofructokinase-1
Fructose 1,6-bisphosphate
1,3-Bisphosphoglycerate
Glyceraldehyde 3-phosphate dehydrogenase
Phosphoglycerate kinase
3-Phosphoglycerate
2-Phosphoglycerate
Phosphoglyceratemutase
Pyruvatekinase Pyruva
te
Phosphoenolpyruvate
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Three Physiologically Irreversible Steps Glycolysis
And Gluconeogenesis Are Different
1)Glucokinase/Hesosekinase ---glucose 6-phosphatase
2)phosphofructokinase- 1 --fructose 1,6-bisphosphatase,
Three Physiologically Irreversible Steps Glycolysis
And Gluconeogenesis Are Different
3. pyruvate kinase---------------- A) Pyruvate
carboxylase
B) Phosphoenolpyruvate carboxykinase
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Localization of Gluconeogenesis
1. Most Of The Enzymes Are Found In The Cytosol, But
2. Pyruvate Carboxylase----- Mitochondria
3. Glucose 6-phosphatase------ Lumen Of The Endoplasmic Reticulum
Regulation of gluconeogenesis
General Overview Of Metabolism
(Carbohydrate, Protein, Fat)
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