Carbohydrate Metabolism

EDITED & RECOMPOSED BYLiniyanti D.Oswari,MD.,MNS,MSc.For Block 8Medical student, Sriwijaya University

Carbohydrate MetabolismGlycolysis2.3. Biphospoglycerate (2.3.BPG)GlycogenesisGlycogenolysisHMP shuntGluconeogenesisREGULATION OF METABOLISM BY HORMONES

Carbohydrate Metabolism Overview glycogen

pentose GLUCOSE other sugars pyruvate

acetyl CoA EtOHlactate

TCA cycle ATP

GlucosePyruvateRibose-5-phosphateGlycogenEnergy StoresPentose Phosphate PathwayGlycolysisAdipose

GLYCOLYSISGlucose can also be available from food intake. Glucose is also stored as glycogen (glycogenesis).After gluconeogenesis, glucose is converted from glycogen in liver or muscle for glycolysis. Glycolysis is the break down of a 6 C glucose sugar to two 3C pyruvate.

Central role of liver in metabolismGlucose entering the hepatocyte is phosphorylated by glucokinase to glucose-6-phosphate (G-6-P).Other monosaccharides are also made to G-6-P via gluconeogenesis, then glucose can be stored as glycogen. When we need energy, glycolysis converts G-6-P to pyruvate and acetyl coA to enter Citric acid cycle to produce ATP energy via oxidative phosporylation (aerobic metabolism).

Glycolysis: break down of glucose in cytoplasmGlucose-6-phosphateGlucose-1-phosphateUDP-glucoseGlycogenGlucoseHexokinaseFructose-6-phosphateFructose-1, 6-biphosphateGlyceraldehyde-3-phosphateDihydroxyacetone phosphate (DHAP)GlycerolGlyceraldehyde-1, 3-bisphosphateGlycerate-3-phosphateGlycerate-2-phosphatePhospho-enol-pyruvateNAD + PiNADH + H+ATPATPADPADPH2OH2OPyruvateLactateLactate DehydrogenaseATPADPATPADPATPADP

Glycolysis: Phase 1 and 2Phase 1: Sugar activationTwo ATP molecules activate glucose into fructose-1,6-diphosphateThe 1 and 6 indicate which carbon atom to which they are attached.Phase 2: Sugar cleavage (splitting) Fructose-1,6-bisphosphate (6 Cs) is split into two 3-carbon compounds:Glyceraldehyde 3-phosphate (GAP)

Glycolysis: Phase 3Phase 3: Oxidation and ATP formationThe 3-carbon sugars are oxidized (reducing NAD+); i.e., 2 Hs + NAD NADH2Inorganic phosphate groups (Pi) are attached to each oxidized fragment The terminal phosphates are cleaved and captured by ADP to form four ATP molecules The final products are: Two pyruvic acid moleculesTwo NADH + H+ molecules (reduced NAD+)A net gain of two ATP molecules

Glycolysis has two stages.A. An energy investment phase. Reactions, 1-5. Glucose to two glyceraldehyde -3-phosphate molecules. 2 ATPs are invested.B. An energy payoff phase. Reactions 6-10. two glyceraldehyde 3-phosphate molecules to two pyruvate plus four ATP molecules.-- A net of two ATP molecules overallplus 2 NADH(10 ATP2 ATP= 8 ATP).

GLYCOLYSIS Glucose ATP hexokinase ADP Glucose 6-phosphate phosphogluco- isomerase Fructose 6-phosphate ATPphosphofructokinase ADP Fructose 1.6-bisphosphate aldolase

triose phosphate isomerase Dihydroxyacetone Glyceraldehyde phosphate 3-phosphate

Glyceraldehyde 3-phosphateglyceraldehyde NAD+ + Pi3-phosphate NADH + H+ dehydrogenase 1,3-Bisphosphoglycerate ADPphosphoglycerate kinase ATP 3-Phosphoglyceratephosphoglyceromutase 2-Phosphoglycerate enolase H2O Phosphoenolpyruvate ADP pyruvate kinase ATP Pyruvate

Glycolysis:Embden-Myerhof Pathway Oxidation of glucoseProducts:2 Pyruvate2 ATP2 NADHCytosolic

Summary of Energy Relationships for Glycolysis aerobicInput = 2 ATP1. glucose + ATP glucose-6-P2. fructose-6-P + ATP fructose 1,6 bisphosphateOutput = 4 ATP + 2 NADH1. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+ 2 (1,3 bisphosphoglycerate) + 2 NADH2. 2 (1,3 bisphosphoglycerate) + 2 ADP 2 (3-P-glycerate) + 2 ATP3. 2 PEP + 2 ADP 2 pyruvate + 2 ATPNet =2 ATP and 2 NADH( 8 ATP)

Energy Yield From Glycolysis

glucose 6 CO2 = -2840 kJ/mole

2 ATPs produced = 2 x 30.5 = 61 kJ/mole glucoseEnergy yield = 61/2840 = 2% recovered as ATP- subsequent oxidation of pyruvate and NADH can recover more of the free energy from glucose.

Carbohydrate MetabolismPrimarily glucoseFructose and galactose enter the pathways at various pointsAll cells can utilize glucose for energy productionGlucose uptake from blood to cells usually mediated by insulin and transportersLiver is central site for carbohydrate metabolismGlucose uptake independent of insulinThe only exporter of glucose

Blood Glucose HomeostasisSeveral cell types prefer glucose as energy source (ex., CNS) 80-100 mg/dl is normal range of blood glucose in non-ruminant animals 45-65 mg/dl is normal range of blood glucose in ruminant animals Uses of glucose: Energy source for cells Muscle glycogen Fat synthesis if in excess of needs

Fates of GlucoseFed stateStorage as glycogenLiverSkeletal muscleStorage as lipidsAdipose tissueFasted stateMetabolized for energyNew glucose synthesizedSynthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change

immediately after eating a meal

Glucose MetabolismFour major metabolic pathways:

Energy status (ATP) of body regulates which pathway gets energySame in ruminants and non-ruminants Immediate source of energy Pentophosphate pathway Glycogen synthesis in liver/muscle Precursor for triacylglycerol synthesis

Fate of Absorbed Glucose1st Priority: glycogen storageStored in muscle and liver2nd Priority: provide energyOxidized to ATP3rd Priority: stored as fatOnly excess glucose Stored as triglycerides in adipose

Glycolysis - SummaryGlucose (6C)2 Pyruvate (3C)2 ATP2 ADP4 ADP4 ATP2 NAD2 NADH + H

Glucose UtilizationGlucosePyruvateRibose-5-phosphateGlycogenEnergy StoresPentose Phosphate PathwayGlycolysisAdipose

Three irreversible kinase reactionsprimarily drive glycolysis forward. hexokinase or glucokinase phosphofructokinase pyruvate kinase

These enzymes will be shown to beregulate glycolysis as well.

Pyruvate MetabolismThree fates of pyruvate: Conversion to lactate (anaerobic) Conversion to alanine (amino acid) Entry into the TCA cycle via pyruvate dehydrogenase pathway (create ATP)

Fate of Product of Glycolysis- Pyruvate- Pyruvate is at a central branch point in metabolism. Recall:Aerobic pathway - through citric acid cycle and respiration; this pathway yields far more energy and will be discussed later.

NADH + O2 NAD+ + energyPyruvate + O2 3CO2 + energy

Cori CycleLactate is converted to pyruvate in the liver

Two anerobic pathways:

- to lactate via lactate dehydrogenase - to ethanol via ethanol dehydrogenase

- Note: both use up NADH produced so only 2 ATP per glucose consumed

Pyruvate metabolismConvert to alanine and export to blood

Keto acidAmino acid

Pyruvate Dehydrogenase Complex (PDH)Prepares pyruvate to enter the TCA cycle

Electron Transport ChainTCA CycleAerobic Conditions

1. Lactate Fermentation Enzyme = Lactate Dehydrogenase COO- COO-C=O + NADH + H+ H-C-OH + NAD+CH3 CH3pyruvate lactate

Note: uses up all the NADH(reducing equivalents) produced in glycolysis.

Helps drive glycolysis by using up NADH reversible so pyruvate can beregenerated in alternative metabolism lactate fermentation important in red blood cells, parts of the retina, and in skeletal muscle cells during strenuous exercise.Also important in plants and in microbes growing in absence of O2.

-- Lactate Dehydrogenase (LDH) hasmultiple forms. It is an isozyme.Two polypeptides M and H cometogether to form LDH. It is a tetramerso a mixture is formed:M4, M3H, M2H2, MH3 and H4

M M M H H H H H H H M M M M M M M H H H

Skeletal muscle and liver containpredominantly the M forms;heart the H forms. During andafter myocardialinfarction (heartattack), heartcells die releasingLDH into thecirculation.

Diagnostic.

LACTIC ACID (CORI) CYCLE glucose glucose glucose glucose-6-P glucose-6-Pglycogen glycogen ATP ATP NADH Blood NADH pyruvate pyruvate lactate lactate lactate Liver Muscle

The liver uses most of this lactate tomake glycogen. Only small amountsof free glucose released.

Glycogen can be broken down intoglucose when needed.

Alcoholic Fermentation

COO- CO2 CH2OH H O C=O C + NADH CH3 +CH3 CH3 NAD+pyruvate acetaldehyde ethanol pyruvate decarboxylase- irreversible alcohol dehydrogenase- reversibleNote: NADH used up

- pathway is active in yeast.- second step helps drive glycolysissecond step is reversible reverse is ethanol oxidation, eventially yields acetate, which ultimately goes into fat synthesis.- ethanol acetaldehyde acetate - humans have alcohol dehydrogenase in liver which mainly disposes of ethanol.- acetaldehyde is reactive and toxic.

SummaryGlucoseof Reactions 2 ATP 2 NADH 2 pyruvate2 NADH 2 NADHanaerobic anaerobic 2 ethanol + CO2 2 lactate 2 acetyl CoA + 2 CO2 O2 aerobic 4 CO2 + 4 H2O

-- REGULATION OF GLYCOLYSIS

HEXOKINASE and GLUCOKINASEHEXOKINASE Commiting step in glycolysis: phosphorylation of glucose.Inhibited by its product, glucose6-phosphate, as a response to slowing of glycolysis .found in all cells of every organism low specificity for monosaccharides (simple sugars) i.e., other monosaccharides can be phosphorylated by hexokinase. relatively high affinity for glucose, KM = 0.1 mM

GLUCOKINASE liver enzyme with high KM (10 mM)for glucose so most effective when glucose levels are very high not inhibited by glucose 6-phosphatesensitive to high glucose in circulation from recent meal so it decreases high level of glucose in blood by taking glucose into liver

2. PHOSPHOFRUCTOKINASE rate limiting for glycolysis an allosteric multimeric regulatory enzyme. Measures adequacy of energy levels.

Inhibitors: ATP and citrate high energy Activators: ADP, AMP, and fructose 2,6 bisphosphate low energy

ATP inhibits phosphofructoseactivity by decreasing fructose6-phosphate bindingAMP and ADP reverse ATP inhibition Fructose 2,6 bisphosphate is a very important regulator, controlling the relative flux of carbon through glycolysis versus gluconeogenesis.- It also couples these pathways to hormonal regulation.

3. PYRUVATE KINASE PEP + ADP Pyruvate + ATP An allosteric tetramer inhibitor: ATP & acetyl CoA & fatty acids (alternative fuels for TCA cycle) activator: fructose 1,6-bisphosphate (feed-forward) Phosphorylation (inactive form) anddephosphorylation (active form)under hormone control.Also highly regulated at the level of gene expression(carbohydrate loading)

Siklus 2,3 Biphosphoglicerat

2.3 Biphosphoglycerate(BPG)

Human Hb and binding site for 2,3 BPG

The rate of Glycolysis will influent the affinity oxygen and Hemoglobine,with the intermediate 2,3 BPG pathwayDisorder in glycolysis will influent the affinity hemoglobine and oxygen.Defficiency Piruvat kinase, so the level of 2.3 BPG will increase. The affinity of oxygen and hemoglobine loose, and hypoxia in the tissueAnemia hemolytic.

Deficiency Hexokinase- Genetic disease

- 2.3 BPG in RBC low- Affinity Hb and Oxygen is very strong (abnormal)- Hypoxia in the tissue

Defficiency Piruvate kinase(Anemia Hemolitik)- Blockade The end of glycolytic pathway, The affinity of oxygen and Hb decrease. turun.- The production of ATP is not enough, so it decrease the activity of Na+ & K+, stimulate ion ATP ase pump. It will keep the membran cell of RBC. Defficiency Piruvate Kinase will make RBC Lysis.

GlycogenesisGlycogen synthesisOccurs in cytosol of liver,muscle& kidneyOccurs when blood glucose levels are highExcess glucose is stored (limited capacity)liver and muscle are major glycogen storage sitesliver glycogen used to regulate blood glucose levelsbrain cells cannot live for > 5 minutes without glucosemuscle glycogen used to fuel an active muscle

O O OO -[1- 4] linkages O O O O O O O -[1-6] linkage O ........ CH2OH CH2OHCH2OHCH2OHCH2CH2OH. The glycogen structure showing the glycosidic bonds O

Liver710% of wet weightUse glycogen to export glucose to the bloodstream when blood sugar is lowGlycogen stores are depleted after proximately 24 hrs of fasting (in humans)De novo synthesis of glucose for glycogen Skeletal muscle1% of wet weightMore muscle than liver, therefore more glycogen in muscle, overallUse glycogen (i.e., glucose) for energy only (no export of glucose to blood)Use already-made glucose for synthesis of glycogen

Glycogenesis

Pathway of glycogen synthesis (glycogenesis). GlucoseGlucose-6-phosphateHexokinase(muscle)Glucokinase(liver)ADPATP

Control of enzyme activityRate limiting step

Glikogenesis & GlikogenolisisGlucose anabolismGlucose storage: glycogenesisglycogen formation is stimulated by insulinglucose not needed immediately is stored in the liver (25%) and in skeletal muscle (75%)Glucose release: glycogenolysisconverts glycogen to glucoseoccurs between meals, stimulated by glucagon and epinephrine

Glycogenolysis Glycogen degradationOccurs in cytosolSignal that glucose is needed is given by hormonesepinephrine stimulates glycogen breakdown in muscleglucagon which stimulates glycogen breakdown in liver in response to low BGused to sustain blood glucose level between meals and to provide energy during an emergency/exercise

GlycogenX glycolysis

LIVER PATHWAY Glycogenolysis and the fate of glycogen in liver and kidney (inhibited by lack of fructose-2,6-bisP

. Glycogenolysis and the fate of glycogen in muscle. MUSCLE PATHWAY

SIMPLISTIC SUMMARY:-- Epinephrine and glucagon stimulate glycogenolysis & inhibit glycogenesis via a cAMP and a phosphorylation cascade. release glucose-- Glycogenesis is stimulated by insulin in a pathway ending in the dephosphorylation of glycogen synthase.-- Glycogenolysis is also inhibited via dephosphorylation. take up glucose

Glycogen Storage Diseases: A family of serious, although notnecessarily fatal, diseases caused bymutations in the enzymes involvingin glycogen storage and breakdown.

Glycogen Storage Diseases Type I: Von Gierke Disease; Glucose-6-phosphatase Defect

Hypoglycemia occurs due to defect of the final step of gluconeogenesis. This disease, affects only liver and renal tubule cells Decreased mobilization of glycogen produces hepatomegaly. Decreased gluconeogenesis causes increased lactate leading to lactic acidemia. Type V: McArdle Disease; Skeletal Muscle Glycogen Phosphorylase Defect

Skeletal muscle is affected, whereas the liver enzyme is normal. Temporary weakness and cramping of skeletal muscle occurs after exercise. There is no rise in blood lactate during strenuous exercise. Muscle contains a high level of glycogen with normal structure Type VI: Hers Disease; Liver Glycogen Phosphorylase Defect

Liver is affected, whereas the skeletal muscle enzyme is normal. Marked hepatomegaly occurs due to a high level of glycogen with normal structure.. Following administration of glucagon, there is no increase in blood glucose.

Pentose Phosphate Pathway=Hexose Monophosphat ShuntGeneration of NADPH and PentosesHas 2 functions1.Generate reducing equivalents NADPH (reduced cosubstrate/ coenzyme) needed for fatty acid synthesis, folate reduction2. Produce ribose 5-phosphate needed for DNA and RNA synthesis

Occurs in cytosol of cells particularly important in anabolic tissues,liver, adrenal cortex, mammary glands and fat tissuesmuscle cells do NOT have HMS enzymes

Pentose Phosphate PathwayGlucose-6-phosphate6-Phospho- glucono-lactone6-Phospho- gluconateD-Ribulose-5-phosphateD-Ribose- 5-phosphateRNA or DNA

A scenario in which the cell requires NADPH but does not require ribose-5-P NADPH is used for biosynthetic reactions and glutathione metabolismGlucose-6-P-dehydrogenaseGlyceraldehyde-3-P and fructose-6-P return to the glycolytic pathway

Ribulose 5-PXylulose 5-PRibose 5-P(5 carbons)Sedoheptulose 7-P(7 carbons)Erythrose 4-PTransketolaseTransaldolaseGlyceraldehyde 3-PFructose 6-PFructose 6-PGlyceraldehyde 3-PTDPTDPTransketolase A scenario in which the cell requires ribose-5-P but does not require NADPH Ribose-5-P is the sugar required for the synthesis of nucleic acidsOxidative branch is feedback inhibited by excess NADPH at glucose-6-P dehydrogenaseNucleic acids

GlucoseGlucose 6-PRibulose 5-P6-PhosphogluconateRibose 5-P(5 carbons)ATPADPNADPNADPHCO2NADPHNADPGlucose-6-P-dehydrogenase6-Pgluconate dehydrogenase A scenario in which the cell requires both NADPH and ribose-5-P Nucleic acids

OverviewFunctionNADPH productionReducing power carrierSynthetic pathwaysRole as cellular antioxidantsRibose synthesisNucleic acids and nucleotides

Characteristics: Tissue DistributionDemand for NADPHBiosynthetic pathwaysFA synthesis (liver, adipose, mammary)Cholesterol synthesis (liver)Steroid hormone synthesis (adrenal, ovaries, testes)Detoxification (Cytochrome P-450 System) liverReduced glutathione as an antioxidant (RBC)Generation of superoxide (neutrophils)

Characteristics:Oxidative and Non-oxidative PhasesOxidative phasesReactions producing NADPHIrreversible Non-oxidative phasesProduces ribose-5-PReversible reactions feed to glycolysis

NADPH producing reactionsGlucose-6-P dehydrogenase6-P-gluconate dehydrogenase

The Pentose Phosphate Pathway:Non-oxidative phases

RegulationGlucose-6-P dehydrogenaseFirst stepRate limitingAllosteric RegulationFeedback inhibited by NADPHInducible enzymeInduced by insulin

HMS ( Hexose Monophospat Shunt)Nicotinamide adenine dinucleotide phosphatephosphorylated form of reduced nicotinamide adenine dinucleotide (NADH)generated in a series of reactions comprising the oxidation-reduction phase of HMSRibose 5-phosphatesugar used as the backbone of DNA and RNACells requirement for ATP (glycolysis) or NADPH and ribose 5-P (HMS) determines which path it will take.

Stages of HMSReactions occur in 3 main stagesoxidation-reduction generation of NADPHisomerization stagegeneration of ribose 5-phosphatecarbon bond cleavage-rearrangement stageconversion of three 5-carbon sugars to two 6-carbon sugars (Fructose 6-phosphate) and one 3-carbon sugar (Glyceraldehyde 3-phosphate)these series of reactions occur in cells where demand for NADPH is highF 6 P can be converted back to G 6 P which can re-enter HMS

Reactions of Stages 1 and 2G6P is oxidized to 6-phosphoglucono-lactone by G6P dehydrogenase that uses NADP as coenzyme produces NADPH and 6-phosphoglucono6-phosphoglucono is hydrolyzed (addition of water) to 6-phosphogluconate 6-phosphogluconate is oxidized by 6 phosphogluconate dehydrogenase produces NADPH and ribulose 5 phosphate Ribulose 5-phosphate is isomerized to ribose 5 phosphate

Regulation of Metabolism RevisitedAllosteric Enzyme Modulationenzymes can be stimulated or inhibited by certain compoundsmodulators act by altering conformational structure of their allosteric enzymes causes shifts between relaxed and tight conformationsrelaxed is most activeratio of ADP (or AMP) to ATP is important in regulation of energy metabolism

Allosteric Enzyme Modulationlow ADP:ATP ratio signals less need to produce ATPinhibition of key enzymes in glycolysis and the TCA cyclePFK, PDH, CS, and isocitrate dehydrogenasehigh ADP:ATP ratio signals need for ATPactivation of the above enzymesATP is end product in oxidative catabolism and its accumulation would signal to decrease catabolic pathway activity

Allosteric Enzyme Modulationratio of NADH to NAD+ is also important in regulationNADH is end product of catabolic pathwayaccumulation would signal to decrease activitydiminution would signal to increase activitykey enzymes are affected in glycolytic and TCA cyclePK, PDH, CS, isocitrate dehydrogenase and alpha KG dehydrogenase

Role of NADPH in the RBCProduction of superoxideHb-Fe2+-O2 -> Hb-Fe3+ + O2-.Spontaneous rxn, 1% per hourO2-. + 2H2O -> 2H2O2Both O2-. & H2O2 can produce reactive free radical species, damage cell membranes, and cause hemolysis

Pentose Phosphate PathwayGlucose 6-phosphate dehydrogenase deficiency

Detoxification of Superoxide Anion and Hydrogen PeroxideAntioxidant enzymesSuperoxide dismutaseGlutathione peroxidaseGlutathione reductase

-- GLUCONEOGENESIS --Definition: the biosynthesis of glucose from simpler molecules, primarily pyruvate and its precursors.

pyruvate lactate some amino acid skeletons TCA cycle intermediates

GluconeogenesisOccurs within mitochondriaLactate is made to pyruvate, but this is not the reverse of glycolysisPyruvate carboxylase converts pyruvate to Oxaloacetate with CO2PEPCK (PEP carboxykinase) converts oxaloacetate to PEP (Phosphoenol pyruvate to G-3-P, F-6-P to G-6-P. Glucose-6-phosphatase converts G-6-P to glucose in endoplasmic reticulum

The Cori CycleSkeletal MuscleLiverLactateLactatePyruvatePyruvateGlucose 6-phosphateGlucose 6-phosphateGlucoseGlucosebloodbloodLDH, Lactate DehydrogenaseLDH, Lactate DehydrogenaseHexokinaseGlucose 6-phosphatase

Metabolism in liver (amino acid for gluconeogenesis)Amino acids in the liver can also be converted to pyruvate which is converted to glucose or acetyl coA.Acetyl Co A can be made to fatty acid and triacylglycerols and stored as fat.Fatty acids in the liver can be made to lipids for storage; or converted to acetyl CoA via oxidation when needed.

Gluconeogenesis Synthesis of glucose from non-carbohydrate precursors during fasting in monogastrics

Occurs primarily in liver, but can also occur in kidneys and small intestine Glycerol Amino acids Lactate Pyruvate Propionate There is no glucose synthesis from fatty acidsSupply carbon skeleton

Carbohydrate Metabolism :GluconeogenesisGlucose may be synthesized from other starting materials in a process called gluconeogenesis.Overview

General FeaturesTissues:liver (80%)kidneys (20%)Subcellular location of enzymespyruvate carboxylase: mitochondrialglucose-6-phosphatase: ERall other enzymes cytoplasmic

gluconeogenesis

Malate ShuttleOAA produced in mitochondriamitochondrial membrane impermeable to OAAmalate transporter in mito. Membranemalate dehydrogenase in both mito and cytoNADH produced in cyto also used in gluconeogenesis.

Energetics of GluconeogenesisPyruvate Carboxylase2 ATPsPEP Carboxykinase2 GTPs3-P-glycerate kinase2 ATPsGlyceraldehyde-3-P dehydrogenase2NADH

Precursors for gluconeogenesis

Glycerolderived from adipocyte lipolysishepatic glycerol kinase

Precursors for gluconeogenesisLactateRBCmusclethe Cori Cycle

Precursors for gluconeogenesis

Alanine and other amino acidstransamination of pyruvatepyruvate derived from glycolysis or from amino acid degradationalanine cycle

Coordinated Regulation of Gluconeogenesis and GlycolysisGluconeogenesis and Glycolysis are regulated by similar effector molecues but in the opposite directionavoid futile cyclesPK vs PC&PEPCK PFK-1 vs FDPtaseGK vs G6Ptase

Coordinated Regulation of Gluconeogenesis and GlycolysisRegulation of enzyme quantityFasting: glucagon, cortisolinduces gluconeogenic enzymesrepresses glycolytic enzymesliver making glucoseFeeding: insulininduces glycolytic enzymesrepresses gluconeogenic enzymesliver using glucose

Coordinated Regulation of Gluconeogenesis and GlycolysisShort-term Hormonal EffectsGlucagon, InsulincAMP & F2,6P2PFK-2 & FBPase-2A Bifunctional enzymecAMPInactivates PFK-2Activates FBPase-2Decreases F2,6P2Reduces activation of PFK-1Reduces inhibition of FBPase-1Low blood sugar results inHi gluconeogenesisLo glycolysis

Coordinated Regulation of Gluconeogenesis and GlycolysisAllosteric EffectsPyruvate kinase vs Pyruvate carboxylasePK - Inhibited by ATP and alaninePC - Activated by acetyl CoAFasting results in gluconeogenesisPFK-1 vs FBPase-1FBPase-1 inhibited by AMP & F2,6P2PFK-1 activated by AMP and & F2,6P2Feeding results in glycolysis

REGULATION OF METABOLISM BY HORMONES

Feeding and FastingThe Pancreatic Islet HormonesRegulation of Fatty Acid MetabolismDiabetes Mellitus

Feeding and FastingAs glucose moves via the blood to the liver, insulin from the cells in the pancreas is released to promote glucose uptake by muscle and adipose (for fat storage), and formation of glycogen in liver. Insulin also induce protein synthesis.When the nutrient flow from intestine diminishes (fasting), blood glucose and insulin drop to normal and glucagon is released to prevent hypoglycemia by promoting glycogenolysis and gluconeogenesis in the liver.Insulin can depress glycagon in cells. They have opposing effects on blood glucose levels.

StarvationFuels change from glucose to fatty acids to ketone bodies

FASTINGWell-fedGlucoseG-6-PFructose-6-PFructose-1, 6- bis-PG-6-PFructose-1, 6- bis-PFructose-6-PGlucosePEP (3C)PEPPyruvatePyruvateOxaloacetate- INSULIN ++ Glucagon ---+++CortisolPEPCK

The Pancreatic Islet HormonesPancreasDuodenumSpleenExocrine AciniAlpha cell secretes glucagonBeta cell secretes insulinDelta cell secretes somatostatin (inhibits growth hormone)F cell secretes pancreatic polypeptides for digestion in duodenumAbdominal aortaHepatic arteryHyperglycemia (high blood glucose) stimulatesHypoglycemia (low blood glucose) stimulates

InsulinIncrease glucose uptake in cells.Convert glucose to glycogen (glycogenesis).Increase amino acid uptake and protein synthesis.Promote lipogenesis.Slow down gluconeogenesis and glycogenolysis.Blood glucose level dropsHypoglycemia inhibits release of insulin.

GlucagonActs on hepatocytes.Converts glycogen to glucose (glycogenolysis).Form glucose from lactic acid and amino acids (gluconeogenesis).Glucose released from liver to make blood glucose increase to normal.Hyperglycemia inhibits release of glucagon.

http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm

Otak Memerlukan120 gram glucose / hari = 480 calories

Otak dan pilihan energinyaKebutuhan kalori otak 120 g/ hari glukosa, Hanya Glukosa (Kecuali Bila tidak ada glukosa maka dari Benda-benda keton yang berasal dari lemak dan protein tubuh dg proses Gluconeogenesis)Dalam keadaan istirahat memerlukan konsumpsi oksigen 20% dari kebutuhan total tubuh. Mengapa Otak memerlukan energi sebesar itu? Bagaimana keterlibatan transport Na+K+?Tapi otak tidak ada Glikogen & tidak bisa membentuk glukosa sendiri, kenapa?

Bila tidak cukup tidur maka glukosa diotak jadi sangat rendah. 4 mM glucosesleepno sleepJadi bila tidak cukup tidur, maka glukosa otak turun. Jadi jangan begadang walaupun besok ujian akhir biokimia.

Blood Sugar and Its Regulation

1. The source and fate of blood sugar

Blood sugar level must be maintained within a limited range to ensure the supply of glucose to brain.

The blood glucose concentration is 70-110 mg/dl(3.896.11mmol/L ) normally.

2. Regulation of blood sugar level1insulin for decreasing blood sugar levels.2glucagonfor increasing blood sugar levels.3glucocorticoid: for increasing blood sugar levels.4adrenalinefor increasing blood sugar levels.

3. Abnormal Blood Sugar LevelHyperglycemia: > 200 mg/dlThe renal threshold for glucose:> 200 mg/d Hypoglycemia: < 40-50 mg/dl

Negative FeedbackLiver cellsMuscle and fat cells throughout bodyInsulin carried in bloodEfferent PathwayEffectorsIncreased Insulin secretion and synthesisIntracellular communicationBlood GlucoseBeta Cells in Islets of LangerhansReceptorsGlucose uptakeBlood GlucoseBlood GlucoseGlucose synthesisGlycogensynthesisResponseStimulusTHE REGULATION OF BLOOD GLUCOSE

http://www.medbio.info/Horn/Time%203-4/homeostasis_2.htm

Diabetes MellitusCaused by deficiency of insulin secretion or actionsType I diabetes (10%) is insulin-dependent (IDDM), starts early in life and could become very severe. Due to insufficient insulin secretion and thus injection of insulin is required to save the patients life.Type II diabetes (90%) is non-insulin dependent, NIDDM, which is slow to develop with milder symptoms. Insulin is produced but the cells are not responding (insulin resistant), causing many complications including obesity.

Criteria for the Diagnosis of Diabetes ADA(ADA= American Diabetes Association)

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

A1C 6.5%ORFasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l)*Fasting : no calorie intake at least 8 hoursORTwo-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTTORA random plasma glucose 200 mg/dl (11.1 mmol/l)

Prediabetes: IFG, IGT, Increased A1C (ADA)*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range.ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.

Categories of increased risk for diabetes (Prediabetes)*FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFGor2-h plasma glucose in the 75-g OGTT 140-199 mg/dl (7.8-11.0 mmol/l): IGTorA1C 5.7-6.4%

Correlation of HbA1C with Estimated Average Glucose (eAG)

HbA1c % Mean Blood Glucose Average Plasma Glucose Interpretation(mg/dL)(mg/dL)461 65Non-Diabetic Range5921006124135

7156170 Target for Diabetes in Control

8188205 Action Suggested according 9219240ADA guideline102512751128331012314345

* Sumber : Diabetes Care : 2002 : 25: 275-8.

Biochemical complications of diabetes mellitus.Both types of diabetes fail to uptake glucose, leading to hyperglycemia. Other symptoms of diabetes include thirst and frequent urination.In IDDM, excessive glucagon level (due to lower insulin level) also reduces the level of F-2,6-BP in the liver, and inhibits glycolysis. Gluconeogenesis and glycogen breakdown are also induced. NIDDM produces excessive amount of glucose in blood leading to glucosuria.Excessive glucose is thus produced into the blood leading to hyperglycemia (> 200mg/dl), even with glucose excreted in urine (hence named mellitus).

http://www.mhhe.com/biosci/ap/dynamichuman2/content/gifs/0231.gif

Blood GlucoseFasting blood glucose concentration (person who has not eaten in the past 3-4 hours) Normal person:80 - 90 mg / 100 mlDiabetic patient:110 - 140 mg / 100 ml After a meal: Normal person:120 - 140 mg / 100 mlDiabetic patient:< 200 mg / 100 ml

EXCESS OF BLOOD GLUCOSEExerts high osmotic pressure in extracellular fluid, causing cellular dehydrationExcess of glucose begins to be lost from the body in the urine: GLYCOSURIA

GLYCOSURIA >>>

Excessive glucose in the kidney filtrate acts as an osmotic diuretic, inhibiting water reabsorption resulting in POLYURIA: huge urine output >>> decreased blood volume and dehydration.

Dehydration stimulates hypothalamic thirst centers, causing POLYDIPSIA: excessive thirst.

health.howstuffworks.com/ diabetes1.htm

OTHER SIDE EFFECTS of POLYURIAThe dehydration resulting from polyuria also leads to dry skin.

During a period of dehydration, blurred vision can be caused by fluctuations in the amount of glucose and water in the lenses of the eyes.

http://www.nws.noaa.gov/sec508/htm/low_vision.htm

POLYPHAGIA

POLYURIA, POLYDYPSIA, & POLYPHAGIA= THE 3 CARDINAL SIGNS OF DIABETESPOLYPHAGIA: excessive hunger and food consumption, a sign that the person is starving in the land of plenty. That is, although plenty of glucose is available, it cannot be used, and the cells begin to starve.Without fuel, cells cannot produce energy >> fatigue and weight loss. http://clear.msu.edu:16080/dennie/clipart/

Insulin deficiency >> metabolic use of FATA deficiency of insulin will accelerate the breakdown of the bodys fat reserves for fuel. Free fatty acids become the main energy substrate for all tissues except the brain.Increased lipolysis results in the production of organic acids called ketones (KETOGENESIS) in the liver.

KETOGENESIS>>KETOSIS

The increased ketones in the blood lower the pH of blood, resulting in a form of acidosis called KETOSIS, or ketoacidosis.Ketones are excreted in the urine: KETONURIA.

Complications of KETOSIS:

Serious electrolyte losses also occur as the body rids itself of excess ketones.

Ketones are negatively charged and carry positive ions out with them.

Sodium and potassium are also lost from the body; because of the electrolyte imbalance, the person get abdominal pains and may vomit, and the stress reaction spirals even higher.

Can result in coma, deathhttp://www.sla.purdue.edu/academic/fll/JapanProj/FLClipart/Medical/vomit.gif

Effects of insulin deficiency on metabolic use of fat

Excess fat metabolism leads to an increase in plasma cholesterol >>> increased plaque formation on the walls of blood vessels.

Leads to atherosclerosis & other cardiovascular problems: cerebrovascular insufficiency, ischemic heart disease, peripheral vascular disease, and gangrene.

Effects of insulin deficiency on metabolic use of fatDegenerative changes in cardiac circulation can lead to early heart attacks. Heart attacks are 3-5 times more likely in diabetic individuals than in nondiabetic individuals. The most common cause of death with diabetes mellitus is myocardial infarction.

Other complications of diabetes:A reduction in blood flow to the feet can lead to tissue death, ulceration, infection, and loss of toes or a major portion of one or both feet. Damage to renal blood vessels can cause severe kidney problems. (Nephropathy)Damage to blood vessels of the retina can also causeblindness. (Retinopathy) http://my.diabetovalens.com/infocus/feafeb0404.asp

Non-Proliferative RetinopathyBlood vessels in the retina leak and hemorrhage. Patient may notice a decrease in vision if the swelling and hemorrhage affect the macula.

Macula edema is the most common cause of visual loss in diabetic retinopathy.

Non-Proliferative Diabetic RetinopathyFundus photo of normal macula Hemorrhages in non-proliferative diabetic retinopathy http://www.neec.com/Vitreoretinal_Disease_Diabetic_Retinopathy.html

Proliferative RetinopathyNew blood vessels grow in the eye.

These new blood vessels tend to bleed and leak causing vision loss.

These new blood vessels may also pull on the retina causing retinal detachment.

Proliferative Diabetic RetinopathyNew blood vessel growth around optic nerve in proliferative diabetic retinopathy Hemorrhage from new blood vessel growth in proliferative diabetic retinopathy http://www.neec.com/Vitreoretinal_Disease_Diabetic_Retinopathy.html

Side Effects of Excess SugarLoss of vision due to cataracts: Excessive blood sugar chemically attaches to lens proteins, causing cloudiness.

Skin infections sometimes occur because excess sugar in the blood suppresses the natural defense mechanism like the action of white blood cells. And sugar is an excellent food for bacteria for food to grow in.

BACTERIA CELLS

PeriodontitisHigh blood glucose also helps bacteria in the mouth to grow, making tooth and gum problems worse.

Gingivitis: bacteria grow in the shallow pocket where the tooth and gum meets; gum begins to pull away from the tooth. Progresses to:

Periodontitis: infection causes actual bone loss, teeth begin to pull away from the jaw itselfhttp://www.stevedds.com/periodon.htm

Latter Stages of Periodontitishttp://www.qualitydentistry.com/dental/periodontal/perio/sperio.html

Damage to the NervesNumbness and tingling in feet and night leg cramps may result from nerve damage due to prolonged high glucose levels that cause changes in the nerves and neuron starvation from lack of cellular glucose.

Nerve damage can also lead to a loss of the ability to feel pain in the feet, leading to undue pressure>>calluses>> ulceration. (Neuropathy)

Diabetic NeuropathyNeuropathy can result in two sets of what appear to be contradictory problems. Most patients who have neuropathy have one these problems but some can be affected by both:

1) symptoms of pain, burning, pins and needles or numbness which lead to discomfort

2) loss of ability to feel pain and other sensation which leads to neuropathic ulceration

Diabetic NeuropathyPatients with neuropathy lose their sensation of pain. As a result, they exert a lot of pressure at one spot under the foot when they walk, building up a callus at that site without causing discomfort. The pressure becomes so high that eventually it causes breakdown of tissues and ulceration.

www.thefootclinic.ca/services_diabetic.php

www.diabetes.usyd.edu.au/foot/Neurop1.htmlwww.thefootclinic.ca/services_diabetic.phpA TYPICAL NEUROPATHIC ULCER IS

1) PAINLESS2) SURROUNDED BY CALLUS3) ASSOCIATED WITH GOOD FOOT PULSES (BECAUSE THE CIRCULATION IS NORMAL)4) AT THE BOTTOMOF THE FOOT& TIPS OF TOES

IncreasedlipolysisINSULINDEFICIENCYPolyphagia Increasedfree fatty acids (FFA)GlycosuriaHyperglycemiaVolume depletionDIABETICCOMAPolyuriaPolydipsiaIncreased FFA oxidation (liver)KetoacidosisEFFECTS OF DECREASED INSULIN

Glucose and insulin secretionBLOOD GLUCOSETIME (MIN)5101520PLASMAINSULINCONCENTRATION

GLUCOSE TOLERANCEGlucose tolerance is the bodys ability to manage its blood sugar level within normal range. The Cori cycle is a strategy used by the body to accomplish this. The blood sugar of normal individuals can sometimes drop to the hypoglycemic level.This can even be caused by ingesting too much sugar, trig- gering the release of extra insulin.

TOO MUCH OF A GOOD THINGDiabetics use insulin injections to treat high blood glucose levels. It is essential that blood glucose levels always be maintained above a critical level. Brain cells use only glucose for energy. When blood glucose levels fall too low (20 to 50 mg/ml), symptoms of hypoglycemic shock develop nervous irritability leading to fainting, seizures and coma

Type I vs. Type II Diabetes

Type I (IDDM)Type II (NIDDM)Age at onsetUsually under 40Usually over 40Body weightThinUsually overweightSymptomsAppear suddenlyAppear slowlyInsulin producedNoneToo little, or it is ineffectiveInsulin requiredMust take insulinMay require insulinOther namesJuvenile onset diabetesAdult onset diabetes

How does exercise help? Most of the time muscle tissue depends on fatty acids for energy Under two conditions muscles use large amounts of glucose:During moderate or heavy exercise (muscle fibers become permeable to glucose even in the absence of insulin important in Type I) During the few hours after a meal (while pancreas is secreting more insulin important in Type II). Most of the glucose is stored as muscle glycogen.http://clear.msu.edu:16080/dennie/clipart/exercise.gif

The Diabetic Meal Plan

Under this plan, 60 to 70 percent of your total daily calories should come from grains, beans, and starchy vegetables, with the rest being meat, cheese, fish and other proteins.

Fats, oils, and sweets should be used sparingly. The Diabetes Food Pyramid suggests the following daily servings of food for people with diabetes:http://shots.oxo.li/food/vegetables.jpg

The Diabetes Food Pyramid differs from the standard Food Guide Pyramid in the way that it groups different foods together.

Because blood glucose is of primary concern to people with diabetes, the Diabetes Food Pyramid focuses on the way in which certain foods affect blood glucose levels.

For example, in the standard pyramid, beans and legumes are grouped with meats, due to their protein content. In the diabetes pyramid, however, beans are grouped with starches, because they affect blood glucose in the same way that starchy foods do.

http://nema.cap.ed.ac.uk/teaching/odl/odl5/insulin.jpgOne final look at the homeostatic mechanismin question:In diabetes, where is the missing link?Can you rememberall of the biochemical consequences???The physicalconsequences??Quite a bit for one little feedback loop, heh?

Lactose Intolerance(Lack or absent of Lactase)Lactase acts as a pair of molecular scissors:It snips the disaccaride lactose in two simple sugars, galactose and glucose:

Clinical manifestations Lactose intoleranceAbdominal pain crampy, localized to periumbilical area, or lower quadrantBloated feeling,stomach crampsFlatulence

Diarrhea

Vomiting

Stools are usually bulky, frothy and watery

Dietary lactose restrictionHighest concentration in milk and ice-cream, much lower quantities in cheese

Complete restriction of lactose-containing foods should be necessary for a limited period to ascertain the specificity of the diagnosis

Since patients can tolerate graded increases in lactose intake, small quantities of lactose may subsequently be reintroduced into the diet, with careful attention to development of symptoms

Enzyme replacementCommercially available lactase preparations (bacterial or yeast beta galactosidases)

Lactaid, Lactrase, LactAce, DairyEase and Lactrol

Start with two Lactaid tablets with lactose ingestion, and adjust both the Lactaid dose and the lactose load to tolerance

Calcium intakeAvoidance of milk and other dairy products can lead to reduced calcium intake, and increase in risk of osteoporosis and fractureCalcium carbonateTums popular and effectiveInfants and young children liquid calcium gluconateYogurt containing lactose is well tolerated by the patients. The yogurt contains live cultures of bacteria that produce lactase

Learning ObjectiveCompare Aerobic & anaerobic GlycolysisCompare gluconeogenesis and glycogenolysis, and explain how insulin & Glucagon affects these processes.What are the role of HMP Shunt in our bodyHow the Carbohydrate & Fat metabolism di Diabetic Patients.Why diabetic patient easy suffer KetoacidosisExplain the consequences of using low carbohydrate and high protein diet for weigh loss plan. What is the role of leptine on dieting?Why untreated diabetes may die?

IMT Depkes 2002-2004Cara Menghitung IMT(Index Massa Tubuh)IMT=Berat Badan (Kg) Tinggi Badan(m)2

Arti IMT(BMI= Body Mass Index): < 17.0 = Sangat kurus17.0 - 18.4 = Kurus18.5 - 25.0 = Normal25.1 - 27.0 = Gemuk > 27.0 = Obes

Kebutuhan energi ManusiaGambaran Energi digunakan Kkal/hariWanita dewasa normal700 2000Laki-laki dewasa normal2400 2800Pasien Bed rest1300 1800Bayi baru lahir350 450Remaja perempuan aktif2400 2600Remaja pria aktif 3100 - 3600

Energi yang digunakanAktifitas Kkal/mnt Duduk sambil istirahat 0.7 2.0Berjalan2.0 6.0Lari cepat15 atau lebihLari jarak jauh/Maraton10 atau lebihBalap sepeda 10 atau lebih

Rumus Harris BennedictFrequently the calculated BMR is referred to as BEE = Basal Energy expenditureHarris BennedictBEE female: 655 + 9.7( W kg) + 1.85 (Ht cm) 4.7 (Age)

BEE male: 66.5 + 13.75 (W kg) + 5 (Hg cm) 6.8 (A)Total Energy: BEE + Physical activity + TEF

Factors Affecting BMRIncrease:growthlean body mass & tallmaleFever, stresspregnancy/lactationincrease in thyroxin

Thermal Effect of FoodTEF = Thermal effect of foodIncreased energy expenditure after a meal.5-10% of BMRCost of digestion, absorption, & assimilation of nutrientsEx: 5% x 1320 = 60 Cal

Total EnergyTE = BMR +TEF + ActivitiesActivities: Any voluntary activitiesSedentary 25-35% BMRLight 35-50%Moderate 50-70%Heavy >70%http://www.americaonthemove.org/USATODAY.com - Study: Obesity rises faster in poor teens

TE ExampleIf BMR = 1200Then TEF x 0.1 = 120If Activity is moderate = 1200 x 0.5 = 600Then TE = BMR +TEF + ActivityTE = 1200 + 120 + 600 = 1920

Energy BalanceWhen E (in) = E (out)no weight changeWhen E (in) < E (out)weight lossWhen E (in) > E (out)weight gain

Tujuan Pengelolaan Obesitas1)Menurunkan BB sekitar 5-10% dari BB awal, dan bila ada indikasi dapat diteruskan sampai BMI 25 atau BMI 26.92)Mencegah terjadinya Sindroma Yoyo, ialah meningkatnya BB kembali yang oleh karena disiplin penderita yang turun 3)Memperbaiki penyakit komorbid yang ada 4)Memperbaiki Kualitas Hidup

Pengobatan & perawatan nutrisi pada Obesitas:

Sasaran dari intervensi adalah: 1. Penurunan lemak tubuh untuk mencapai berat badan diantara 20% Berat badan ideal 2. Jangan Turunkan BB dengan drastis. (Maksimal 0.5-1 kg/mg)3.Buatlah kebiasaan makan yang lebih sehat. (Tinggi serat, rendah kalori, rendah lemak dan gula)4. Cegah kehilangan otot selama penurunan berat badan. 5.Modifikasi Prilaku & Olahraga teratur6. Pertahankan penurunan berat badan7. Bila tidak berhasil gunakan Obat Sibutramin (Reductil)- Sudah ditarik tahun 2010OrlystatPenggunaan Teh ( diuretika & stimulansia)

Keuntungan dari OlahragaFig. 5-2, p. 111Memperbaiki pencernaan & metabolisme lemak.

*******************************************************************************************************Table 2, current diagnostic criteria for the diagnosis of diabetes, is divided into five slidesOn this slide, all four criteria are included:A1C 6.5%Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l)Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTTA random plasma glucose 200 mg/dl (11.1 mmol/l), in patients with classic symptoms of hyperglycemia or hyperglycemic crisis

The subsequent slides examine each of the four criteria in greater detail

*ReferenceAmerican Diabetes Association. Standards of medical care in diabetes2011. Diabetes Care 2011;34(suppl 1):S13. Table 2.In 1997 and 203, The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus1,2 recognized an intermediate group of individuals whose glucose levels, although not meeting criteria for diabetes, are nevertheless too high to be considered normalThis group was defined as having impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)IFG: fasting plasma glucose (FPG) of 100-125 mg/dl (5.6-5.9 mmol/l)IGT: two-hour plasma glucose (2-h PG) on the 75-g oral glucose tolerance test (OGTT) of 140-199 mg/dl (7.8-11.0 mmol/l)It should be noted that the World Health Organization (WHO) and a number of other diabetes organizations define the cutoff for IFG at 110 mg/dl (6.1 mmol)Individuals with IFG and/or IGT have been referred to as having prediabetes, indicating a relatively high risk for future development of diabetesIFG and IGT should not be viewed as clinical entities in their own right but rather risk factors for diabetes as well as cardiovascular disease (CVD)IFG and IGT are associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertensionIndividuals with an A1C of 5.7-6.4% should be informed of their increased risk for diabetes as well as CVD and counseled about effective strategies to lower their risks (see Prevention/Delay of Type 2 Diabetes)*ReferencesExpert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197. Genuth S, Alberti KG, Bennett P, et al., for the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003;26:3160-3167.American Diabetes Association. Standards of medical care in diabetes2011. Diabetes Care 2011;34(suppl 1):S13. Table 3.**Children and pregnant women have higher BMRsTall people have a larger surface area, so their BMRs are higher. Lean tissue more ActiveBody Temperature: For every increase of 0.5C in internal temperature of the body, the BMR increases by 7 percent. The chemical reactions in the body actually occur more quickly at higher temperatures. So a patient with a fever of 42C (about 4C above normal) would have an increase of 50 percent in his BMR. External Temperature: Exposure to cold temperature causes an increase in the BMR, so as to create the extra heat needed to maintain the body's internal temperature. A short exposure to heat has little effect on the body's metabolism as it is compensated mainly by increased heat loss. But prolonged exposure to heat results in a gradual decrease in the BMR.

Thyroxin is key regulator of BMR. The more thyroxin produced the higher the BMR

Diet induced thermogenesis, metabolic cost of digestion, absorption, metabolism and storing nutrients after a meal

Increased body temp for several hours.

5-10% varies depending on amounts and types of foods consumed.

Inc amts---inc TEF

Inc fat---dec TEF (easy to store) (2-3%)

Inc CHO (6-8%)or Protein(15-30%)---inc TEF

Example:

BMR=1200

TEF = 1200 x .01 = 12

Activity = 1200 x .5 = 600

TE = 1200 + 12 + 600 = 1812How does one lose weight? Decrease Ein and increase EoutIntake vs BMR + actiivity + TEF

If only dec intake there is an increased chance of regaining, increased chance of weight cycling.Gain weight? Physical activity and eat more often

*

Documents

Carbohydrate Metabolism