1. 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

2. Chapt. 27 Carbohydrates digestion Fig. 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 starch Cellulose is fiber

3. Glycosidases cleave carbohydrates Overview 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 colon Fig. 2

4. Disaccharidases Fig. 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

5.  -glycosidase complex Fig. 9  -glycosidase complex: glycoprotein Anchored as phosphtidylglycan to COOH end Lactase hydrolyzes lactase Other enzyme does glycolipids (glucose-ceramide) Fig. 10.6

6. Fiber Fig. 10 Fiber is indigestible carbohydrates Colonic bacteria metabolize leftover saccharides Generate gas (H 2, CO 2, CH 4 ) Lactate Short fatty acids Acetic, butyric Some absorbed by body Incomplete digestion products lead to diarrhea

7. 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

8. Absorption of sugars Fig. 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 transporters

9. Insulin and GLUT4 Figs. 13,14 Insulin stimulates glucose transport into muscle and adipose cells by increasing transporters Glucose goes through cells blood-brain barrier

10. Synthesis of glycogen Fig. 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 metabolism

11. Glycogen synthesis and degradation Fig. 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 paths Glycogen synthase Branching enzyme Degradation: Debrancher enzyme Glycogen phosphorylase

12. Glycogen synthesis and degradation Figs. 28.5,6 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 PO 4 )

13. 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 PO 4 inhibit Phosphorylase kinase Glycogen phosphorylase PO 4 activates Phosphatases remove PO 4 Dotted lines decreased in fasting state Fig. 8

14. Muscle glycogenolysis Fig. 11 Exercise activates muscle glycogenolysis: Initiated by muscle contraction, nerve impulse or epinephrine AMP allosteric activator of glycogen phosphorylase (Fig. 9.8) Nerve signal Ca 2+ release, binds calmodulin (Fig. 9.10) Activates phosphorylase kinase Epinephrine through PKA activates same phosphorylase kinase Result: active PO 4 Glycogen phosphorylase and glucose-1-P

15. Ch. 29 Pentose phosphate pathway, fructose, galactose Fig. 1 fructose Metabolism of other sugars: Fructose – common in diet Sucrose, high fructose corn syrup Galactose – from lactose 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’

16. Fructose Fig. 3 Fructose is metabolized to intermediates of glycolysis Fructokinase forms F-1-PO 4 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

17. 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

18. Pentose phosphate pathway Fig. 2 Pentose phosphate pathway: Bypass of part of glycolysis Generates NADPH (reducing power) Biosynthesis fatty acids Cholesterol, DNTP, Detox reactions 5-C sugars (ribose PO 4 ) Can rearrange back into glycolysis compounds Regulation by cell needs

19. 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

20. Gluconeogenesis Fig. 1* 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)

21. Gluconeogenesis occurs in mitochondrion and cytosol Fig. 5 Gluconeogenesis: Complex conversion of pyruvate back to PEP (vs. oxidation of PEP by pyruvate kinase, PDC) Mitochondrion, cytosol Gluconeogenesis is highly regulated

22. Blood glucose sources Fig. 20 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

23. 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

24. 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: a.Both children have the disease b.Neither child has the disease c.Jill has the disease, not Jack d.Jack has the diasese, not Jill e.There is not enough information to make a determination