After Digestion And Absorption Of Food What Next?.

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

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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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