Chapts 27-31 topicsChapt. 27 Carbohydrates digestionGlycosidases cleave carbohydratesDisaccharidasesB-glycosidase complexFiberLactose intoleranceAbsorption of sugarsInsulin and GLUT4Synthesis of glycogenGlycogen synthesis and degradationSlide 12Regulation of glycogen metabolism is criticalMuscle glycogenolysisCh. 29 Pentose phosphate pathway, fructose, galactoseFructoseGalactosePentose phosphate pathwayGluconeogenesis essentialsGluconeogenesisGluconeogenesis occurs in mitochondrion and cytosolBlood glucose sourcesReview question Chapt 27Review question Ch. 29Chapts 27-31 topicsChapts. 27-31 Carbohydrate topics Student Learning Outcomes:• Explain basic processes of digestion, absorption and transport of carbohydrates (and lactose intolerance)•Describe formation, degradation of glycogen•Describe essentials of other sugar metabolism:•Pentose phosphate path, fructose, galactose•Describe the basic path of gluconeogenesisChapt. 27 Carbohydrates digestionFig. 1 sugars Carbohydrates are major source of calories (~40%)•Digested by specific enzymes:•Starch (plants) - -amylase•Lactose – -galactosidase, lactase•Sucrose - sucrase•High fructose syrup•Isomerized from starchCellulose is fiberGlycosidases cleave carbohydratesOverview of carbohydrate digestion, absorption-amylases (saliva, pancreas)•Saliva starts breakdown•Pancreatic enzyme in intestine•Disaccharidases in intestine•Monosaccharides enter blood through intestinal epithelium facilitative diffusion transporters or Na+-dependent glucose transporters•Fiber and remaining compounds digested by bacteria in colonFig. 2DisaccharidasesFig. 4,5 Disaccharidases located in intestinal brush border•Hydrolyze disaccharides•Anchored in membrane•Transmembrane N-end•Are glycosylated•Two enyzme activities•Table 1•Ex. Sucrase-isomaltase:• 1,4 bond• 1,6;  1,4-glycosidase complexFig. 9 -glycosidase complex: glycoprotein•Anchored as phosphtidylglycan to COOH end•Lactase hydrolyzes lactase•Other enzyme does glycolipids (glucose-ceramide)Fig. 10.6FiberFig. 10 Fiber is indigestible carbohydrates•Colonic bacteria metabolize leftover saccharides•Generate gas (H2, CO2, CH4)•Lactate•Short fatty acids•Acetic, butyric•Some absorbed by body•Incomplete digestion products lead to diarrheaLactose intoleranceLactose intolerance: (see Table 2)• Low levels lactase (late-onset) • Adult levels are low in many populations• Injestion of lactose → pain, nausea, flatulence, diarrhea•Can mix lactase enzyme with food firstAbsorption of sugarsFig. 12 Sugars are absorbed through intestinal epithelia:•Glucose through Na+-dependent transporters: •let in Na+ and glucose, galactose also (can concentrate)•Glucose through facilitated transport (GLUT 1-5)•Different isoforms•12 membrane-spans•Fructose and galactose Use glucose transportersInsulin and GLUT4Figs. 13,14 Insulin stimulates glucose transport into muscle and adipose cells by increasing transporters•Glucose goes through cells blood-brain barrierSynthesis of glycogenFig. 28. 1,2 Chapt. 28 Synthesis, degradation of glycogen 1.4 glycosidic,  1,6 branches, •protein glycogenin on end•Major role in liver is blood glucose•Major role in muscle is ATP•Some people have defects glycogen metabolismGlycogen synthesis and degradationFig. 3 Different enzymes for synthesis, degradation•Starts and ends with glucose-1-Phosphate•Careful regulation•Synthesis:UDP-G pyrophosphorylasecosts 1 UTP (2 P~P) eachUDP-G other pathsGlycogen synthaseBranching enzyme•Degradation: Debrancher enzyme Glycogen phosphorylaseGlycogen synthesis and degradationFigs. 28.5,6 Glycogen has branch every 8-10 glucose residuesSynthesis:branching helps: solubility more sites for synthesis and degradationDegradation:Phosphorylase uses Pi to breakBranching enzyme does residues near branchBranch sugar yield glucose(not PO4)Regulation of glycogen metabolism is criticalRegulation of glycogen in liver:•responds to hormones glucagon, epinephrine via cAMP, PKA Reciprocal phosphates activate, inhibit:•Glycogen synthase PO4 inhibit•Phosphorylase kinase•Glycogen phosphorylase PO4 activates•Phosphatases remove PO4Dotted lines decreased in fasting stateFig. 8Muscle glycogenolysisFig. 11 Exercise activates muscle glycogenolysis:Initiated by muscle contraction, nerve impulse or epinephrine•AMP allosteric activator of glycogen phosphorylase (Fig. 9.8)•Nerve signal Ca2+ release, binds calmodulin (Fig. 9.10)Activates phosphorylase kinase•Epinephrine through PKA activates same phosphorylase kinaseResult: active PO4Glycogen phosphorylaseand glucose-1-PCh. 29 Pentose phosphate pathway, fructose, galactoseFig. 1 fructoseMetabolism of other sugars: •Fructose – common in diet•Sucrose, high fructose corn syrup•Galactose – from lactoseMetabolized to glycolysis intermediates Hereditary defect diseases•Pentose phosphate pathForms reducing power (NADPH) for detoxification, biosynthesisForms 5-C sugars for nucleotides‘bypass part of glycolysis’FructoseFig. 3Fructose is metabolized to intermediates of glycolysis•Fructokinase forms F-1-PO4Essential fructosuria people lack enzyme•Aldolase critical: 3 isoforms All do glycolysis F 1,6-P Only Aldolase B Cleaves F-1-P Hereditary fructose intolerance: can be fatal: accumulate F-1-P in liver impaired gluconeogenesis, glycogenolysis; hypoglycemiaGalactoseGalactose is converted to Glucose-1-P• Galactokinase forms Gal-1-P•Galatose 1-P uridylyltransferase forms Glucose 1-P uses UDP-glucose and forms UDP-galactose•Epimerase can regenerate UDP-glucoseLot of galactose from Lactose; Classic galactosemic accumulates Gal-1-P liver, impaired glycogen synthesisFig. 5Pentose phosphate pathwayFig. 2Pentose phosphate pathway: •Bypass of part of glycolysis•Generates NADPH (reducing power)•Biosynthesis fatty acidsCholesterol, DNTP, •Detox reactions•5-C sugars (ribose PO4)•Can rearrange back into glycolysis compounds•Regulation by cell needsGluconeogenesis essentialsGluconeogenesis in the liver makes glucose:•Critical need for glucose especially red blood cell, brain•During fasting, liver mobilizes glycogen, makes new glucose from noncarbohydrates•(see also Chapters 1-3) Fig. 2GluconeogenesisFig. 1*Gluconeogenesis:•Main precursors are lactate, glycerol, amino acids•Many steps are reversals of glycolysis reactions•3