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iochemistry for Health Science Carbohydrate Metabolism
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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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iochemistry for Health Science Carbohydrate Metabolism
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GLYCOLYTIC PATHWAY
5/3/2010 8Malate-aspartate shuttle
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iochemistry for Health Science Carbohydrate Metabolism
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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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iochemistry for Health Science Carbohydrate Metabolism
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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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iochemistry for Health Science Carbohydrate Metabolism
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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
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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
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