ch09 cho metabolism

8/9/2019 CH09 CHO Metabolism

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iochemistry for Health Science Carbohydrate Metabolism

hatchawin Petchlert, Ph.D. 1

CARBOHYDRATECARBOHYDRATEMETABOLISMMETABOLISM

Chatchawin Petchlert, Ph.D.Chatchawin Petchlert, Ph.D.Dept. of BiochemistryDept. of BiochemistryFac. Of Science, Burapha UniversityFac. Of Science, Burapha University

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CatabolismCatabolism of proteins, fats,of proteins, fats,

and carbohydrates in the 3and carbohydrates in the 3

stages of cellular respirationstages of cellular respiration..

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Digestion

MouthMouth 60% starch+30% sucrose60% starch+30% sucrose-amylase (ptyalin) +10% lactose+10% lactose

StomachStomach

pancreaspancreaspancreatic amylase

Small IntestineSmall Intestineoligosaccharidase

disaccharidase

MonosaccharidesMonosaccharides

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Absorption

Absorb at small intestineAbsorb at small intestine

Absorption mechanism of eachAbsorption mechanism of each

monosaccharide is differentmonosaccharide is different

Glucose : active transport or facilitate diffusionGlucose : active transport or facilitate diffusion

Fructose : facilitate diffusionFructose : facilitate diffusion

Galactose : same the glucoseGalactose : same the glucose


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GLYCOLYTIC PATHWAY

5/3/2010 8Malate-aspartate shuttle


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Glycerol-3-phosphate shuttle5/3/2010 10

CORI CYCLE

Muscle

Glucose

glycolysis

Pyruvate

LDH (M4)

Lactic acid

Blood

Glucose

Lactic acid

Heart

Glucose

gluconeogenesis

Pyruvate

LDH (H4)

Lactic acid

Isozyme Lactate dehydrogenase = ?Isozyme Lactate dehydrogenase = ?

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Pyruvate Utilization

PEP (C3)PEP (C3) EtOH

CytoplasmCytoplasm pyruvate kinase +ATP Acetaldehyde

(Anaerobic)(Anaerobic) Pyruvate (C3)Pyruvate (C3) LactateLactate

MitochondriaMitochondria Pyruvate (C3)Pyruvate (C3)

(Aerobic)(Aerobic) pyruvate DH cpx. COCO22 ++ NADH

Acetyl CoA (C2)Acetyl CoA (C2)

TCA CycleTCA Cycle

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Lactic acid Fermentation


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Alligators are normallyAlligators are normally

sluggish and torpid. Yet whensluggish and torpid. Yet when

provoked these animals areprovoked these animals are

capable of lightningcapable of lightning--fastfast

charges and dangerouscharges and dangerous

lashings of their powerfullashings of their powerful

tails. Such intense burst oftails. Such intense burst of

activity are short and must beactivity are short and must be

followed by long periods offollowed by long periods of

recovery.recovery. The fast emergencyThe fast emergency

movements requiremovements require lacticacid fermentation to generateto generate

ATP in skeletal muscles. TheATP in skeletal muscles. The

stores of muscle glycogenstores of muscle glycogen

are rapidly expended inare rapidly expended in

intense muscular activity, andintense muscular activity, and

lactate reaches very highlactate reaches very high

concentrations in musclesconcentrations in musclesand extracellular fluid.and extracellular fluid.

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Ethanol Fermentation

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LactaseLactase--specific antibodies heavily label thespecific antibodies heavily label theintestinal microvilli of aintestinal microvilli of a lactose tolerant adult.adult.

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Intestinal microvilli from aIntestinal microvilli from a lactose intolerant adultadultshow little or no labeling with the same antibody.show little or no labeling with the same antibody.

5/3/2010 19 5/3/2010 20OxidativeReactionsofthePentose

OxidativeReactionsofthePentose--phosphatePathway

phosphatePathway


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NonNon--Oxidative Reactions of the PentoseOxidative Reactions of the Pentose--phosphate Pathwayphosphate Pathway

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Pentose Phosphate Pathway or HMS

II OxidationOxidation

GG--66--PP66--PP--gluconolactonegluconolactone66--PP--gluconategluconate

66--PP--gluconategluconateRibuloseRibulose--55--PP

IIII Isomerization and RearrangementIsomerization and Rearrangement

RibuloseRibulose--55--PPRiboseRibose--55--P (R)P (R)

XyluloseXylulose--55--P (X)P (X)

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Pentose Phosphate Pathway or HMS

IIII Isomerization and RearrangementIsomerization and Rearrangement

C5 (X)C5 (X) C3C3 C6C6transketolase transaldolase

C5 (R)C5 (R) C7C7 C4C4 C6C6

transketolase

C5 (X)C5 (X) C3C3

Thiamin pyrophosphate (TPP) and MgThiamin pyrophosphate (TPP) and Mg2+2+

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Role of NADPH and glutathione in protecting

cells against highly reactive oxygen species.

Reduced glutathione (GSH) protects the cell by

destroying H2O2 and OH. Regeneration of GSH

from its oxidized form (GSSG) requires theNADPH produced in the G6PDH reaction.

NADPH is used togenerate reducedglutathione (GSH). GSHplays a critical role in

quenching theoxyradicals in the cells.

If NADPH generation isinhibited due to themutations in G6PDH,cells become susceptibleto oxidative damage.

Malaria parasite is verysensitive to Oxy-radicals,and people with G6PDHdefect are resistant tomalaria as the parasite iskilled by oxy-radicals.


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Pyruvate dehydrogenase complex

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Electron micrograph of pyruvate dehydrogenase complexes isolated fromE. coli, showing the subunit structure.


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Krebs cycle or TCA cycle orCitric acid cycle

Acetyl CoA

Oxaloacetate Citrate

NADH cis-aconitate

L-Malate Isocitrate

NADH

Fumarate -ketoglutarate

FADH2 NADH

Succinate Succinyl CoA

GTP

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Anapleurotic ReactionsAnapleurotic Reactions

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Electron Transport System

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Electron Transport System

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Electron Transport System andOxidative Phosphorylation

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Gluconeogenesis

The synthesis of glucose from differentThe synthesis of glucose from different

compoundscompounds

Cytoplasm and MitochondriaCytoplasm and Mitochondria Most of reactions are reversible glycolyticMost of reactions are reversible glycolytic

reactionsreactions exceptexcept 3 irreversible points3 irreversible points

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Gluconeogenesis

PyruvatePyruvatePEPPEPI Pyruvate CBx : pyruvateOAA

Mitochondria

II Malate DH : OAAmalate

III Malate DH : malateOAACytoplasm

IV PEP CBxKinase : OAAPEP

FF--1,61,6--DPDPFF--66--PP by F-1,6-diphosphatase

GG--66--PPGlucoseGlucose by G-6-phosphatase

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Glycogenolysis

Occur in the liver after fasting stage or heavyOccur in the liver after fasting stage or heavy

exerciseexercise

Hydrolyze each of (Hydrolyze each of (114)4)glucose byglucose by

phosphorylasephosphorylase until remain 4 residues thatuntil remain 4 residues thatlinked with branched pointlinked with branched point

EnzymeEnzyme glucan transferaseglucan transferase will hydrolyze 3will hydrolyze 3

residuesresidues

The remainder will hydrolyze byThe remainder will hydrolyze by amyloamylo--

(1(16)6)--glycosidase (debranching enzyme)glycosidase (debranching enzyme)

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Glycogenesis Occur in every tissues but especially in liver andOccur in every tissues but especially in liver and

musclemuscle

Glucose + PGlucose + P GG--66--PP

GG--66--PP GG--11--P byP by phosphoglucomutasephosphoglucomutase GG--11--P + UTPP + UTP UDPUDP--Glucose (UDPG)Glucose (UDPG) byby UDPGUDPG--

pyrophosphorylasepyrophosphorylase

UDPG is linked with [gluUDPG is linked with [glu--glu]glu]nn byby glycogenglycogen

synthetasesynthetase [glu[glu--glu]glu]n+1n+1

AmyloAmylo--1,41,41,61,6--transglucosidase (branchingtransglucosidase (branching

enzyme)enzyme) will build the branched pointwill build the branched point

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OUTSIDEOUTSIDE

MEMBRANEMEMBRANE

INSIDEINSIDE

ATPATP cAMP

inactive

protein kinase

R

G adenylate cyclase

Active

protein kinase

Glycolysis

Hormone and Metabolism

I

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The role of carbohydrate inmaintenance of health

NutrientsNutrients Glycemic homeostasis, GIGlycemic homeostasis, GI

integrity and functionintegrity and function

Energy balanceEnergy balance Lipogenesis / insulinLipogenesis / insulin

resistantresistant

ExerciseExercise Carbohydrate loadingCarbohydrate loading

Memory and Cognitive functionMemory and Cognitive function

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Carbohydrate and Diseases

ObesityObesity

NonNon--insulin dependent diabetes mellitusinsulin dependent diabetes mellitus

(NIDDM)(NIDDM)

Cardiovascular diseaseCardiovascular disease CancerCancer

GastroGastro--Intestinal diseasesIntestinal diseases constipation, hemorrhoid, diverticularconstipation, hemorrhoid, diverticular

diseasedisease

Dental cariesDental caries


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Diabetes Mellitus

HyperglycemiaHyperglycemia

InsulinInsulin

Normal serum glucoseNormal serum glucose

before mealbefore meal 7070--115 mg/dl115 mg/dl

2h after meal2h after meal140 mg/dl140 mg/dl

SymptomsSymptoms

Increase urine secretion, thirsty, weightIncrease urine secretion, thirsty, weight

loss, thinner, fatigue, hungryloss, thinner, fatigue, hungry

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Diabetes Mellitus

Insulin dependent diabetes mellitusInsulin dependent diabetes mellitus

(IDDM)(IDDM)

-- always occur in young periodalways occur in young period

-- cannot produce insulincannot produce insulin

-- serious symptomsserious symptoms

(Diabetic ketoacidosis ; DKA)

-- insulin is essential for this diabetic typeinsulin is essential for this diabetic type

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Diabetes Mellitus

NonNon--insulin dependent diabetes mellitusinsulin dependent diabetes mellitus

(NIDDM)(NIDDM)

-- always occur in adult period (always occur in adult period (>>>>>>>> 40y)40y)

-- can produce insulin but loss activitycan produce insulin but loss activity

-- little or serious or no symptomslittle or serious or no symptoms

(Hyperosmolar hyperglycemic nonketotic

coma)

-- control diet alone or also use tablets /control diet alone or also use tablets /

inject insulininject insulin

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Diabetes Mellitus

Screening Test by Fasting plasmaScreening Test by Fasting plasma

glucose (FPG)glucose (FPG) after 12-h fasting

FPGFPG


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Diabetes Mellitus

Oral glucose tolerance test (OGTT)Oral glucose tolerance test (OGTT)

Patient:

1. Must have carbohydrate diet1. Must have carbohydrate diet 150150g/day forg/day for 3 days3 days

2. Normal daily activity2. Normal daily activity

3. No illness or stress3. No illness or stress

4. No drugs effect to glucose tolerance4. No drugs effect to glucose tolerance

such assuch as --blocker, nicotinic acid,blocker, nicotinic acid,steroidsteroid5/3/2010 62

Diabetes Mellitus

Oral glucose tolerance test (OGTT)Oral glucose tolerance test (OGTT)

Method:

1. Morning test after 101. Morning test after 10--h fastingh fasting

2. Screening test for FPG2. Screening test for FPG

3. Give 75 g glucose in 300 ml water for 53. Give 75 g glucose in 300 ml water for 5 minmin

4. While testing, a patient must be resting, no4. While testing, a patient must be resting, no

smoking and no drinkingsmoking and no drinking

5. Test every 30 min for 2h (before loading5. Test every 30 min for 2h (before loading

glucose, 1/2 h, 1h, 1 1/2 h and 2h afterglucose, 1/2 h, 1h, 1 1/2 h and 2h after

loading glucoseloading glucose (American Diabetic Association andNational Diabetic Data Group)

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Diabetes Mellitus

Normal value of serum glucose (beforeNormal value of serum glucose (before

breakfast)breakfast)

child


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Relation of Carbohydrate and Cancers

Sugars :Pancreas

Resistant starch: Colon, rectum

NSP / fibre :Stomach

Insufficient

Starch : Stomach

Sugar : Colon,rectum

Sugar : StomachStarch : Colon,rectum

NSP / fibre :Pancreas,colon, rectum,breast

Possible

IncreasesIncreases

RiskRiskNoNo

RelationshipRelationshipDecreasesDecreases

RiskRiskEvidenceEvidence

NSP = Non-starch polysaccharides

ch09 cho metabolism

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