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Chapts 27-31 topics. Chapts. 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:
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Chapts 27-31 topics • Chapts. 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 gluconeogenesis
Chapt. 27 Carbohydrates digestion • Carbohydrates are major source of calories (~40%) • Digested by specific enzymes: • Starch (plants) - a-amylase • Lactose – b-galactosidase, lactase • Sucrose - sucrase • High fructose syrup • Isomerized from starch • Cellulose is fiber Fig. 1 sugars
Glycosidases cleave carbohydrates • Overview of carbohydrate • digestion, absorption • a-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 colon Fig. 2
Disaccharidases • Disaccharidases located in intestinal brush border • Hydrolyze disaccharides • Anchored in membrane • Transmembrane N-end • Are glycosylated • Two enyzme activities • Table 1 • Ex. Sucrase-isomaltase: • a 1,4 bond • a 1,6; a 1,4 Fig. 4,5
B-glycosidase complex • b-glycosidase complex: glycoprotein • Anchored as phosphtidylglycan to COOH end • Lactase hydrolyzes lactase • Other enzyme does glycolipids (glucose-ceramide) Fig. 10.6 Fig. 9
Fiber • 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 diarrhea Fig. 10
Lactose intolerance • Lactose 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 first
Absorption of sugars • 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 transporters Fig. 12
Insulin and GLUT4 • Insulin stimulates glucose transport into muscle and adipose cells by increasing transporters • Glucose goes through cells blood-brain barrier Figs. 13,14
Synthesis of glycogen • Chapt. 28 Synthesis, degradation of glycogen • a 1.4 glycosidic, a 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 metabolism Fig. 28. 1,2
Glycogen synthesis and degradation • 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 paths Glycogen synthase Branching enzyme • Degradation: • Debrancher enzyme • Glycogen phosphorylase Fig. 3
Glycogen synthesis and degradation • Glycogen has branch every 8-10 glucose residues • Synthesis: • branching helps: • solubility • more sites for synthesis • and degradation • Degradation: • Phosphorylase uses • Pi to break • Branching enzyme does • residues near branch • Branch sugar yield glucose • (not PO4) Figs. 28.5,6
Regulation of glycogen metabolism is critical • Regulation 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 PO4 • Dotted lines decreased • in fasting state Fig. 8
Muscle glycogenolysis • 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 kinase • Result: active PO4 • Glycogen phosphorylase • and glucose-1-P Fig. 11
Ch. 29 Pentose phosphate pathway, fructose, galactose • Metabolism of other sugars: • Fructose – common in diet • Sucrose, high fructose corn syrup • Galactose – fromlactose • Metabolized to glycolysis intermediates • Hereditary defect diseases • Pentose phosphate path • Forms reducing power (NADPH) for detoxification, biosynthesis • Forms 5-C sugars for nucleotides • ‘bypass part of glycolysis’ Fig. 1 fructose
Fructose • Fructose is metabolized to intermediates of glycolysis • Fructokinase forms F-1-PO4 • Essential 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; hypoglycemia Fig. 3
Galactose • Galactose 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-glucose • Lot of galactose from Lactose; Classic galactosemic accumulates Gal-1-P liver, impaired glycogen synthesis Fig. 5
Pentose phosphate pathway • Pentose phosphate pathway: • Bypass of part of glycolysis • Generates NADPH (reducing power) • Biosynthesis fatty acids Cholesterol, DNTP, • Detox reactions • 5-C sugars (ribose PO4) • Can rearrange back • into glycolysis compounds • Regulation by cell needs Fig. 2
Gluconeogenesis essentials • Gluconeogenesis 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. 2
Gluconeogenesis • Gluconeogenesis: • Main precursors are lactate, • glycerol, amino acids • Many steps are reversals of glycolysis reactions • 3 critical irreversible steps • have separate enzymes • (these also regulated) Fig. 1*
Gluconeogenesis occurs in mitochondrion and cytosol • Gluconeogenesis: • Complex conversion of pyruvate back to PEP • (vs. oxidation of PEP by pyruvate kinase, PDC) • Mitochondrion, cytosol • Gluconeogenesis is • highly regulated Fig. 5
Blood glucose sources • Sources of blood glucose in fed, fasting, starved • Liver uses glycogenolysis • Muscle uses its glycogen, not contribute to blood level (lack G-6-Phosphatase) • Gluconeogenesis spares • body protein Fig. 20
Review question Chapt 27 • After digestion of a piece of cake that contains flour, milk and sucrose as its primary incredients, the major carbohydrate products that enter the blood are which of the following: • a. glucose • b. fructose and galactose • c. galactose and glucose • d. fructose and glucose • e. glucose, galactose and fructose
Review question Ch. 29 • 29.1 Hereditary fructose intolerance is a rare recessive genetic diseases that is most commonly caused by a mutation in exon 5 of the aldolase B gene. The mutation creates a new AhaII recognition sequence. To test for the presence of the disease, DNA was extracted from parents and their two children; After PCR and enzyme digestion, DNA run on gel: • Which conclusion can be made: • Both children have the disease • Neither child has the disease • Jill has the disease, not Jack • Jack has the diasese, not Jill • There is not enough information • to make a determination