Carbohydrate metabolism modified

CARBOHYDRATE METABOLISM

DR JAYESHPOST GRADUATE STUDENT

DEPARTMENT OF ORAL AND MAXILLOFACIAL SURGERY

INTRODUCTION TO CARBOHYDRATESCARBOHYDRATES AT A GLANCE

CLASSIFICATION OF CARBOHYDRATESMETABOLISMCATABOLISM

DIGESTION AT A GLANCEABSORPTION OF GLUCOSE

GLUCOSE METABOLISMGLYCOLYSIS AND STEPS IN GLYCOLYSIS

IMPORTANCE OF LACTATEENERGETICS OF GLYCOLYSIS

FATE OF LACTATEBPG PATHWAY

PYRUVATE AND ITS FATEACETYL CoA AND ITS IMPORTANCE

CITRIC ACID CYCLE AND ITS IMPORTANCE AND DEFECTS OF THE CYCLEELECTRON TRANSPORT CHAIN

HEXOSE MONOPHOSPHATE SHUNT PATHWAYGLYCOGEN METABOLISM

ERRORS ASSOCIATED WITH CARBOHYDRATE METABOLISMCONCLUSION

BIBLIOGRAPHY

CONTENTS

1. Carbohydrates are the main sources of energy in the body. Brain cells and RBCs are almost wholly dependent on carbohydrates as the energy source. Energy production from carbohydrates will be 4 k calories/g (16 k Joules/g).2. Storage form of energy (starch and glycogen).3. Excess carbohydrate is converted to fat.4. Glycoproteins and glycolipids are components of cell membranes and receptors.5. Structural basis of many organisms: Cellulose of plants; exoskeleton of insects, cell wall of microorganisms, mucopolysaccharides as ground substance in higher organisms.

CARBOHYDRATES AT A GLANCE

-The general molecular formula of carbohydrate is Cn(H2O)n-Carbohydrates are polyhydroxy aldehydes or ketones or compounds which yield these on hydrolysis

Monosaccharide

Disaccharide

Oligosaccharides

Polysaccharides

CLASSIFICATION OF SUGARS

CERTAIN EXAMPLES

Thousands of chemical reactions are taking place insdie a cell in a organised , well coordinated manner, all these reactions are collectively called as METABOLISMIts purpose is to1. Obtain energy2. Synthesis of various bio molecules3. Various metabolic pathways are taking place which are regulate by a. Thru allosteric enzymes. Affected by effector moleculeb. Hormonesc. DNA4. Metabolism is of 2 typesA. Catabolism- energy rich molecules aredegraded to simpler

molecules B. Anabolism – synthesis of complex molecules from precursor

molecules

METABOLISM

Has 3 stages1. Primary metabolism – occurs in GI tract.

Converts macromolecules to smaller molecuels2. Secondary/intermediatory – the products are

absorbed and then catabolised to smaller components which in mitochondria form NADH of FADH which takes part in electron transport chain

3. Tertiary/ internal/cellular respiration – ETC where the energy is released

CATABOLISM

-Carbohydrates in the food are complex molecules,-Cooking makes the molecules simpler .-The digestion starts in the oral cavity where saliva(salivary alpha amylase) acts on the complex molecules. It hydrolyses them to form monosaccharides-Gastric hydrochloric acid neutralizes the salivary amylase-pancreas alpha amylase cleaves random alpha 1-4 glycosidic links to form random subunits like maltose, isomaltose, etc- In Intestin there are enzymes like maltase, isomaltase etc which then break these molcules to monosaccharides

BEGINING OF DIGESTION

STAGES OF DIGESTION

Monosaccharides are only absorbed from the intestine. Galactose >glucose > fructose is the order of absorption

ABSORPTION

From lumen to intestinal wallA. By sodium dependent Glucose Transporter 1 (SGluT-1)

ABSORPTION OF GLUCOSE

B. Into the bloodThe intestinal cells have a different mechanism on membrane facing capillaries.By mechanism called glucose transporter type 2 (GLuT2)Sodium independent system. Also called as uniport system

Ping pongmechanism

SUMMARY TILL NOW

GLUT4

Brief history

GLUCOSE METABOLISM

Preferred source of energy with blood and brain exclusively depending on it

Minimal glucose is always required for proper functioning of body

Fasting glucose is 70 – 110 mg/dl

IMPORTANCE OF GLUCOSE

Glycolysis= glyks+lysis Sweet splitting

( embden-meyerhof pathway )Def- in the pathway glucose is converted to pyruvate (aerobic condition) or lactate(anaerobic condition), along with the production of energy .

*It occurs in all the cells cytoplasm*

METABOLISM OF GLUCOSE

• In all the cells• Only source of energy for erythrocytes• During strenous exercise glycolysis provides energy by anaerobic

glycolysis• 1° step for complete oxidation• Gives the basic carbon skeleton for synthesis of amino acids and faty

acids in body• Most reactions are reversible

GLYCOLYSIS

Preparatory

phase

Glucose phosphorylated to glucose 6 phosphateEnzyme hexokinase a key glycolytic enzyme

Glucokinase is found in liver which is under influence of insulin

Once phosphorylated the glucose 6 phosphate cant go out and its final fate is written .

STEP 1

1. Glycolysis2. Glucose3. Glycogen4. Shunt pathway

GLUCOSE 6 PHOSPHATEFATES

Glucose 6 phosphate is isomerised to fructose 6 phosphate Enzyme isomerase

STEP 2

Fructose 6 phosphate -> fructose 1,6 bis phosphateEnzyme phosphofructokinase

STEP 3

glyceraldehyde 3 phosphate aldolase triose phosphate isomerase Fructose 1,6 bisphosphate dihydroxyacetone phosphate

Both the molecules are isomersNet result we have 2 molecules of Glyceraldehyde 3 phosphate

STEP 4

Glyceraldehyde 3 phosphate is dehyrogenated and phosphorylated

It forms 1,3 bis phosphoglycerate with the help of a NAD+ and iP

Enzyme is glyceraldehyde 3 phosphate dehydrogenaseProduct has a high energy bond

STEP 5

One ATP molecule is generated1,3 bisphosphoglycerate forms an ATPBisphophoglycerate is the enzyme here

STEP 6

3 phosphoglycerate is isomerised to 2 phosphoglycerate Enzyme is phosphoglucomutase

STEP 7

2 phosphoglycerate is converted to phosphoenol pyruvateEnzyme is enolase

STEP 8

Phosphoenol pyruvate is dephosphorylated to pyruvateEnzyme is pyruvate kinase

STEP 9

In anaerobic conditionsPyruvate converted to lactateEnzyme lactate dehyrpgenase

STEP 10

REGULATION

In step 5 NAD is a limiting coenzyme as it forms NADH+ and gets reduced

Reverse can be done by oxidative phosphorylationDuring anaerobic conditions when pyruvate is converted to

lactate NAD is formedThus regenerating it for the 5° step

IMPORTANCE OF LACTATE

ENERGY YIELDAEROBIC CONDITION

In aerobic condition

ENERGY YIELDS

ENERGY YIELD IN ANAEROBIC CONDITION

Under anaerobic conditions lactate is producedThe lactate is then again converted back to glucose by

CORI’S cycle in the liver

FATE OF LACTATE

Def :- It is the process by which glucose molecules areproduced from non-carbohydrate precursors. These

include lactate, glucogenic amino acids, glycerol partof fat and propionyl CoA derived from odd chain

fatty acids

GLUCONEOGENESIS

Irreversible steps in Corresponding keyglycolysis gluconeogenic enzymes1.Pyruvate kinase (Step 9) Pyruvate carboxylase;2.Phosphoenol pyruvate carboxykinase3.Phosphofructokinase (Step 3) Fructose-1,6-bisphosphatase4.Hexokinase (Step 1) Glucose-6-phosphatase

Pyruvate to Phosphoenol pyruvate is a irreversible reaction

STEP 1

Malate-Aspartate Shuttle. MDH = malatedehydrogenase. AST = Aspartate amino transferase.

Glu= Glutamic acid. AKG = alpha ketoglutaric acid

MALATE ASPARTATE SHUTTLE

In the cytoplasm, PEPCK enzyme then convertsoxaloacetate to phosphoenol pyruvate by removing

a molecule of CO2

PHOSPHOENOL PYRUVATE CARBOXY KINASE

The phosphoenol pyruvate undergoes furtherreactions catalyzed by the glycolytic enzymes to

form fructose-1,6-bisphosphate

PARTIAL REVERSAL OF GLYCOLYSIS

Fructose 1,6-bis-phosphate is then acted upon byfructose 1,6-bisphosphatase to form fructose

-6-phosphate. This will bypass the step of PFKReaction ie step 3 of the glycolysis

Fructose-1,6-bisphosphataseFructose-1,6- ––––––––––––––––→ Fructose-6-

bisphosphate phosphate + Pi

FRUCTOSE-1,6-BISPHOSPHATASE

The glucose 6-phosphate is hydrolysed to freeglucose by glucose-6-phosphatase.

Glucose-6-phosphate + H2O -----→ Glucose + Pi

GLUCOSE-6-PHOSPHATASE REACTION

1. Only liver can replenish blood glucose2. During starvation gluconeogenesis maintains

the blood glucose level.Energy requirement

LactateGlucogenic amino acids(Alanine, glutamic acid, aspartic

acid,etc)

Glycerol

SIGNIFICANCE OF GLUCONEOGENESIS

SUBSTRATES

RAPAPORT-LEUBRING CYCLEBPG PATHWAY

 In erythrocytesEnzyme is bisphosphoglycerate mutase

• Reduces affinity of the Hb to o2 so it helps unloading the oxygen

• In hypoxic condition also it helps to unload the o2

SIGNIFICANCE

Pyruvate CarboxylaseFructose-1,6-bisphosphatase

ATPHormonal Regulation of Gluconeogenesis

REGULATION

PYRUVATE

FATES OF PYRUVATE

Pyruvate is formed in cytoplasmThe acetyl coa is metabolised in the mitochondria

The process of pyruvate entering the mitochondria and formation of acetyl coa is done by process oxidative

decarobxylationIt has 5 co enzyme and 3 apo enzyme

PYRUVATE DEHYDROGENASE COMPLEX

MECHANISM

Only step which forms the acetyl coaCompeltely irreversible

This step commits the molecule to the electron transport chain

Acetyl CoA can be used to form fatty acids

IMPORTANCE

DEFICIENCY

ACETYL COA

CITRIC ACID CYCLE

HISTORY

Final common pathway that oxidises acetyl CoA to CO2Source or reduced coenzymesthat provide substrate for

respiratory chainActs as link between catabolic and anabolic pathways

Precursor of amino acid synthesis

FUNCTIONS

THE CYCLE

Formation of citric acid Enzyme is citrate synthatase

Is irreversible

STEP 1

Formation of isocitrateEnzyme is acotinase

STEP 2

Formation of alpha keto glutarateEnzyme is isocitrate dehydrogenase

STEP 3

Formation of succnyl coAEnzyme alpha ketoglutartedehydrogenase

STEP 4

The next stage is a substrate level phosphorylationEnzyme here is succinate thiokinase

STEP 5

Formation of fumarateEnzyme is a flavoprotein

STEP 6

Addition of water to form malate from fumarateEnzyme is fumarase

STEP 7

Regeneration of oxaloacetateEnzyme is malate dehydrogenase

NADH is formed from NAD which is utilized in ETC

STEP 8

IN SHORT

1. generation of 2 molcules of CO22. Generation of 10/12 ATP molecules

3. Final pathway in oxidation of all major food

SIGNIFICANCE OF TCA CYCLE

4. Integration of all major metabolic pathwaysCarbohydrate- acetyl CoA enter the pathway

Fats->fatthy acids-> beta oxidation->Acetyl CoAKetogenic amino acids ->Acetyl CoA

5. Fats need oxaloacetate for breaking down to produce energy and oxaloacetate is produced via pyruvate

6. Excess glucose is stored as neutral fat but fat cant be changed to glucose

Because pyruvate to acetyl CoA is absolutely irreversible

7. No net synthesis of carbohydratez as the pyruvate cant be formed fromacetyl CoA

8. Amino acids can enter the cycle for energy production

DEFECTS

1. Citrate and citrate synthatase- ATP acts as allosteric inhibitor . It stop the citrate synthatase. Citrate also allosteriaclly inhibits PPK to stop formation of acetyl

CoA2. ATP is inversely related to the speed of TCA cycle. More

the ATP slower is the cycle and less the ATP faster is the TCA cycle

3. Hypoxia stops the ETC leading to accumulation of NADH and FADH leading to stopping of the TCA

REGULATION OF THE TCA

METABOLIC DEFECTS ASSOCIATED WITH TCA

CYCLE

ELECTRON TRANSPORT CHAIN

ALSO CALLED AS RESPORATORY CHAINIs the final stage where the production of energy takes

placeAlso called as tertiary or internal metabolism

total energy by one molecule

glucose 2850KJ/mol

ELECTRON TRANSPORT CHAIN

It occurs in the membrane of the mitochondria

TRANSPORT OF REDUCING EQUIVALENTS THRU RESPIRATORY

CHAIN

ATP generation, old and new valuesATP generation by Old value PresentlyNADH 3 2.5FADH 2 1.5Glucose 38 32 Acetyl CoA 12 10Palmitate 129 106

HEXOSE MONOPHOSPHATE SHUNT PATH

The glucose molecule instead of going thru normal path is shunted to this pathway hence called

Instead of bisphosphate intermediate there are monophosphate

Also the reaction involves pentose phosphate intermediate Hence its called

hexose monophosphate shunt pathway

AN INTRODUCTION

The pathway has 2 phasesa. Oxidative

b. Non oxidativeThe pathway is used to metabolise upto 10% glucose daily and RBC and liver utilize it upto 30% to produce energy

PATHWAY is a major source for1. Production of NADH

2. Pentose sugars for production of nucleic acids

Glucose 6 phosphate is oxidized forming 2 NADPH

1 pentosephosphate1 molecule of CO2

OXIDATIVE PATHWAY

Pentose phosphate is converted to inermediate in glycolysis

NON OXIDATIVE PHASE

One molecule of NADPH is formedEmzyme is Glucose 6 phosphate dehydrogenase

A. OXIDATIVE PHASE1° STEP

Lactone is hydrolysedEnzyme is dehydrogenase

STEP 2

Oxidative step couples with dehydrogenase6 phospho glucanatedehyrdogenase

2° NADPH is formed

STEP 3

IsomerizationRibulose 5 phosphate is isomerized to ribose 5 phosphate

Or epimerised to xyluslose 5 phosphate

B. NON OXIDATIVE PHASESTEP 4

Transketolase reaction

STEP 5

Transaldolase reaction3 C unit from sedoheptulose 7 phosphate to glyceraldehyde

3 phosphateIt forms fructose 6 phosphate

Donor is ketose and acceptor is aldehyde

STEP 6

Second transketolase reactionAnother reaction where xylulose 5 P and erythrose 4 p

react 2 C are removed from Xylulose and added erythrose 4

Phosphate to form fructose 6 phosphate and a glyceraldehyde 3 p

STEP 7

Finally 2 glyceraldehyde 3 phosphate combine and form afructose 6 phosphate

STEP 8

HMP pathaway can be summarised as6 glucose 6 phosphate+ 12 NADp+ +7 H2O-----> 5 G6P +12 NADPH + 12

H+ iP

This pathway is not utilized for ATP production

SUMMARY

IMPORTANCE OF THE PATHWAY

Glycogen synthesis and metabolism consists of 2 different pathways

1. GlycogenesisSTEP 1

Activation of glucose

GLYCOGEN METABOLISM

Glycogen synthesisEnzyme is glycogen sythatase

STEP 2

Branching enzyme

STEP 3

GLYCOGEN DEGRADATIONSTEP 1. GLYCOGEN PHOSPHORYLASE

Step 2 debranchingStep 3 phosphofructokinaseStep 4 glucose 6 phosphatase in liver

i. In muscle, the energy yield from one glucoseresidue derived from glycogen is 3 ATP molecules,

because no ATP is required for initialphosphorylation of glucose (step 1 of glycolysis).

ii. If glycolysis starts from free glucose only 2 ATPsare produced.

ENERGETICS

i. The synthetic and degradative pathways are reciprocally regulated to prevent futile cycles.ii. The phosphorylated form of glycogen phosphorylase is active; but glycogen synthase becomes inactive on phosphorylation.The covalently modified phosphorylase is active even without AMP. Active (dephosphorylated) glycogen synthase is responsive to the action of glucose-6- phosphate. Covalent modification modulates the effect of allosteric regulators. The hormonal control by covalent modification and allosteric regulation are interrelated.iii. These hormones act through a second messenger, cyclic AMP iv. The covalent modification of glycogen phosphorylase and synthase is by a cyclic AMP mediated cascade. Specific protein kinases bring about phosphorylation and protein phosphatases cause dephosphorylation

REGULATION

It is a balance between synthesis and degradation of glcogen

GLYCOGEN METABOLISM IN SUMMARY

ERRORS ASSOCIATED WITH CARBOHYDRATE

METABOLISM

1. PRINCIPLES OF BIOCHEMISTRY :- LEHNINGER2. HARPER'S ILLUSTRATED BIOCHEMISTRY - ROBERT K.

MURRAY, DARRYL K. GRANNER, PETER A. MAYES, VICTOR W. RODWELL

3. DM VASUDEVAN - TEXTBOOK OF BIOCHEMISTRY FOR MEDICAL STUDENTS, 6TH EDITION.PDF

BIBLIOGRAPHY