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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