Marks’ Biochemistry Ch 27 – Carbohydrates A Review.

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Transcript of Marks’ Biochemistry Ch 27 – Carbohydrates A Review.

Golans Pharmacology

Marks BiochemistryCh 27 CarbohydratesA Review

Dietary CarbohydratesLargest source of calories in USPlant starchesIn grains, tubers, veggiesAmylopectinStraight-chain glycosyl 1,4, branched 1,6AmyloseStraight-chain glycosyl 1,4Fruits/veggiesSucrose and fructoseFiberNot digestedPlant polysaccharides and lignanAnimal starchesSmall amounts glycogen and glycolipidsMajor dietary from animals = LACTOSEGlucose are NOT requiredCan be synthesizedFructose, galactose, xylulose synthesized from glucose

Carbohydrate DigestionKey: digest carbs to their monosaccharide counterparts!!!Some specificty per digestive enzyme-amylaseBegins in mouthForms -dextrinEndoglucosidase (internal 1,4)Stomach pH inactivatesBicarb and more enzyme released from pancreas to breakdownMaltose (di)Maltotriose (tri)Oligosaccharides = limit dextrans (4-9 glucosyl units)

MonosaccharidesSalivary/Pancreatic Amylase Activity

1,4 glucoseLittle/no activity 1,6/end 1,4No effect sugars other than glucose w/ 1,6pHstomachinactiveshortenedLimit dextrans4-9 glucosyl uits1+ 1,6 bondsBicarb and reactivatedAmylase ActivityReduced inEtOH-induced pancreatitisSurgical removalCystic fibrosisMucus blocks pancreatic ductExocrine pancreas reduced 10%Still may not affect rate starch digestionExcessive secretionProtein/fat digestion more strongly affectedStarch BlockersMarketed for losing weightBased on bean proteinsBlock amylaseNever shown effective in aiding weight lossExcess amylase productionLow stomach pHRecently from wheatMore work required

Brush BorderDietary disaccharidesLactoseSucroseProducts starch digestion

Glycosidases in intestinal brush border cells digest these into monosaccharidesDisplay some homogeneityGlucoamylaseTwo globular domainsEach w/catalytic siteExoglucosidaseBegins at non-reducing ends 1,4Release glucoseStops at 1,6Limit dextran down to isomaltoseActivity progressively along small intestine

Highest activity = ileum

Sucrase-Isomaltase ComplexInserted through membraneProtrudes through lumenIntestinal protease clips to 2 attached units100% hydrolyze sucrose80% hydrolyze maltoseActivity at 1,6

Whatever glucoamylase cant get, this enzyme can!Highest activity = jejunum2 separate unitsPutting it all togetherSucrase-Isomaltase Complex DeficiencySucrose intoleranceDigest normal amounts of starch w/o problemsMaltase activity of glucoamylaseResidual activity of S-I complex

TrehalaseOnly 1 catalytic siteHydrolyzes trehalose bondNot major dietary in USInsectsAlgaeMushroomsOther fungiInadvertently eat and deficiencyNauseaVomitingOther severe GI

-Glycosidase ComplexAka Lactase-GlucosylceramidaseAgain, 2 catalytic sitesVery different structurePhosphatidylglycan anchorLactaseHydrolyzes -bond connecting galactose and glucoseGlucosylceramidaseHydrolyzes -bond b/w glucose and ceramide

Highest activity = jejunum

Indigestible CarbsHigh in amyloseLess hydratedColonic bt have at it!H2, CO2, CH4 (flatus)Short-chain fatty acids (SCFA)LactateWe can absorb the SCFA and lactate for energy use

Lactase DeficiencyNonpersistantIncreases 6-8 weeksRises gestational (27-32 weeks)High 1 month post-partum and declinesDecreases adult levels 5-7 yearsAdult hypolactasiaNormal condition everywhere ELSEAgain think flatulence, diarrhea and H2 = avoidance

Nations with milk-dependency means lactase remain or slightly above infant levels

Lactase DeficiencyIntestinal injuryInjury to absorptive cells diminish lactaseSecondary lactase deficiencyKwashiorkorColitisGastroenteritis(Non)tropical sprueExcessive EtOHOther enzymes present at excessive levelsFirst to be lost, last to recoverDietary FiberInsoluble fiberPlant polysaccharide and lignanCelluloseHemicelluloseligninsH2O-soluble fiberPectinsMucilagesGumsBt flora can metabolizeGas and SCFA (for energy!)25-38 g/day; 14g fiber per 1000 calDisease preventive soluble fibersLower cholesterolBinding bile acidsOats contain -glucanbile resorptionPectin for DM rateabsorptionblood glucose postprandium (after meals)

Sugar AbsorptionSugars have tendency to raise blood sugarEither near-immediate raise or slowly raiseHigh glycemic indexCornflakesPotatoesLow glycemic indexSkim milkyogurt

Facilitative TransportGlucose is polarCannot diffuse across membranesOn serosal surfaceNo energy expenditure!Facilitates transport (ha, gotcha) into capillariesReferred to as GLUT1-5All have 12 membrane-spanning domainsLuminal surface tooFructose tooFacilitated through GLUT familyCan transport glucose, but higher affinity for fructoseGalactose as well

Na+-dependent TransportLuminal sideRequires energy (Na/K-ATPase pump)Cotransport of Na+ and glucose = symport!Galactose too

GLUT MechanismDiffer among tissuesDepend on fx glucose, tissue-specificMostly, rate transport NOT rate-limitingIsoform low Km for glucoseOr present [high]

GLUT MechanismGLUT1RBC aka erythrocyteKm 1-7mMPresent extremely [high]When glucose falls postprandial, glucose still adequateGLUT2Liver Km relatively highMaintenance blood glucoseGLUT4AdiposeInsulin increases availabilityFA and glycerol synthesis from glycolysisSkeletal mmTransport by insulinAvailability for glycolysis, glycogen synthesis

Neural Glucose TransportHypoglycemic when glucose 18-54mg/dLDecreased supply to brainLight-headedDizzinessProgressive into comaSlow rate transport = BBBTight junctionsMust passBloodCSF by GLUT1Basement membraneFinally brain by GLUT3Km of brain 7-11mMVm not much greater than rate glucose utilizationBelow fasting of 80-90mg/dLSignificant effects

Deria VoiderEither reduction or complete avoidanceGI discomfort from inability digest lactoseSymptomatic >25g lactose ingestedYogurt = bt lactaseHard cheese = lactoseHowever milk (products) good source of Ca2+ = supplement or could lead to osteoporosisLactose also in medsAnn SulinPoorly controlled DBHyperglycemiaLack of insulin = lack of glucose uptake GLUT4Accumulates in bloodGlycosylation end productsHbA1cAGEsImportant to add fibers to dietDelay gastric emptyingRetard rate absorptionReduces rate blood glucose risesShould consume low glycemic index foodsEat pasta and riceNot potatoesIncorporate breakfast cerealsNona MelosInability digest sucrose/absorb fructoseConverted to gas by colonic btStool pH 5, positive test for sugarH2-breath testNon-portable device gas chromotagraphyElectrodes measure currentDeficiency in S-I complexNo fx reduction in maltase (glucoamylase)Urine negative test for sugarNot absorbing, no chance to get into blood and thus to be reabsorbed by kidneyJejunal biopsyLactase, sucrase, maltase, trehalase normalEnzymes for fructose normal rangeRequires diet free fruit juices, other foods with fructoseVibrio choleraeGram (-)Enter water sourcePovertyPlumbing primitive/nonexistantAttach brush borderRelease exotoxincAMPNa+, anions, H2O not absorbedCl-, cations secretedDiarrhea can be deadly if >1L/hourNa-dependant transporters NOT affectedCo-admin glucose and Na+Partially correct fluid lossAlso Na+ and amino acid co-admin

Rice water stool