1 / 28

Section 10

Section 10. 8. Distribution of absorbed nutrients. 1/10/06. Digestive disorders. other topics: sweeteners GI hormone summary. aka malabsorption disorders condition nutrient molecular problem lactose intol. lactose ¯ lactase pern. anemia vitamin B 12 ¯ intrinsic factor

edana
Download Presentation

Section 10

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Section 10 8. Distribution of absorbed nutrients 1/10/06

  2. Digestive disorders other topics:sweeteners GI hormone summary aka malabsorption disorders condition nutrient molecular problem lactose intol. lactose ¯ lactase pern. anemia vitamin B12¯intrinsic factor celiac disease gluten* peptide antigenicity gallstones cholesterol crystal formation Hartnup neutral aa's ¯ Na+ aa symport disease * protein in wheat, barley, rye see Harper'sBiochem23 ed: p 620 1

  3. Obesity therapy: lipase inhibition • obesity: causative factor of cardiovascular disease, type II diabetes, cancer • pancreatic lipase a serine esterase (cf. trypsin, etc.: serine proteases) • Xenical (Orlistat) inactivates lipase • contains a reactive ester in a strained-ring moiety* (4-atom ring, a β-lactone) • reacts with active site serine residue of lipase 2 *penicillins contain similar reactive amide, a β-lactam

  4. Obesity therapy: lipase inhibition • obesity: causative factor of cardiovascular disease, type II diabetes, cancer • pancreatic lipase a serine esterase (cf. trypsin, etc.: serine proteases) • Xenical (Orlistat) inactivates lipase • contains a reactive ester in a strained-ring moiety* (4-atom ring, a β-lactone) • reacts with active site serine residue of lipase • does not inhibit systemic lipases: e.g., adipocyte lipase, lipoprotein lipase in capillaries (slide 14) • recommended therapy: dose producing ~30% decrease in fat absorption 2 *penicillins contain similar reactive amide, a β-lactam

  5. Overview-review nutrients digestion, absorption glucose, amino acids, fats distribution precursors, available fuels metabolism macromolecules, energy, end products 1

  6. Distribution of absorbed nutrients • alternating statesabsorptive (feeding) postabsorptive (fasting) • absorptive statehyperglycemia, hyperlipemia, hyperaminoacidemia 3

  7. Distribution of absorbed nutrients • alternating statesabsorptive (feeding) postabsorptive (fasting) • absorptive statehyperglycemia, hyperlipemia, hyperaminoacidemia • events or functions during absorptive state • supply fuel for immediate need • replenish proteins • restore glycogen consumed • storage of excess nutrients as fat 3

  8. 1 2 Liver: fate of monosaccharides glc, fructose, galactose, mannose, etc glc-6P glycogen glc derivatives: glucuronate glucosamineetc 4

  9. 1 2 3 Liver: fate of monosaccharides glc, fructose, galactose, mannose, etc glc-6P glycogenglc derivatives:acetyl CoA glucuronateNADPH, etc glucosamineetcfatty acids TG (to adipocytes via lipoproteins: VLDL) excess 4

  10. 1 2 Liver: fate of amino acids amino acids synthesis: synthesis: liver & other aa plasma choline proteins bile salts creatine etc 5

  11. 1 2 3 Liver: fate of amino acids amino acids synthesis: synthesis: pyruvate, Krebs cycle liver & other aa intermediates plasma choline proteins bile salts acetyl CoA, fats, glc creatineetc excess 5

  12. 1 2 Liver: fate of triglycerides (TGs, TAGs) & VLDL remnants^ triglycerides (via chylomicron remnants) glycerol + FA glucose acetyl CoA steroids: cholesterol, bile salts, etc fuel 6

  13. 1 2 3 Liver: fate of triglycerides (TGs, TAGs) & VLDL remnants^ triglycerides (via chylomicron remnants) apolipoproteins glycerol + FA phospholipids glucose acetyl CoA steroids: plasma cholesterol, lipoproteins bile salts, etc(to adipose, other tissues) excess fuel 6

  14. Major plasma lipoproteins: composition Average percent composition lipoprotein protein phospho- chol chol triglyc- class lipids esters erides chylomicron 2 8 2 4 84 chylomicronremnant 6 24 6 12 52 very low densitylipoprotein (VLDL) 5 15 7 13 60 low densitylipoprotein (LDL) 20 20 10 30 20 high densitylipoprotein (HDL) 50 30 4 12 4 7

  15. Major Plasma Lipoproteins sters chylomicron chylomicronremnant very low densitylipoprotein (VLDL) low densitylipoprotein (LDL) high densitylipoprotein (HDL) 8

  16. Major plasma lipoproteins: function lipoprotein class main transport functionchylomicron lipids: intestine → liver, adipose very low density TG: liver → adipose, others lipoprotein (VLDL) low density chol: liver → peripheral tissues lipoprotein (LDL) high density chol: peripheral tissues → liver lipoprotein (HDL) 9

  17. Transport by lipoproteins Lehninger et al., 3rd ed., Fig. 21-38 gif 150% 10

  18. Plasma lipoprotein structure Stryer 4edFig. 27-20 Fig. 26-16 • nonpolar lipid core covered by a shell of amphiphilic PL & protein • protein has surface with information controlling binding, exit & entry ofparticles at specific target cells • on LDL, it is apolipoprotein B–100that binds to LDL receptor proteinon target cell surface • cf. chylomicron: lect. 7, sl 16 cf. Lehninger et al., 3rd ed., Fig. 21-37 cholesterol phospholipid cholesteryl ester apolipoprotein B-100 11

  19. Packaging for transport Lehninger et al., 3rd ed., Fig. 17-2 apolipo-proteins Lehninger et al., 2nd ed., Fig. 16-2 chylomicrons • particles for transport of lipids to liver & adipocytes • size: 0.1–1 µm • average composition: TG (84%) chol (2%) cholE (4%) PL (8%) apolipoproteins (2%) PL chol PL 16 cholE, TG

  20. LDL & its receptor (cf. S7L4sl13) cholesterol: • transported to peripheral cells via LDL • used for cell membrane synthesis or stored as esters • represses transcription of LDL receptor gene LDLreceptors (membranesynthesis) cholesteryllinoleate cholesterol cholesteryloleate(storage) protein LDL amino acids Adapted fromFig. 12-40 ↓receptor synthesis binding →endocytosis→ lysosomalhydrolysis regulatoryactions: → 12

  21. Fate of nutrients: other cells • glucose uptake by facilitated diffusion • most cells: GLUT1 & GLUT3 • muscle & adipose: GLUT4 • insulin stimulates movement of vesicles containing GLUT4 to plasma membrane (S9L2sl19) • adipose: glucose supplies precursors for synthesis of triglycerides • glycerol P • e–s (NADPH) • acetyl CoA • amino acid uptake by facilitated diffusion • muscle: insulin required (transport proteins analogous to GLUT4) 13

  22. insulin binding activates exocytosis Insulin & GLUT4 • at high [glc],facilitated diffusionmediated by GLUT4(muscle & adipose) • similar mechanismoperates fortransport of amino acidsinto muscle GLUT4(glucosetransporter) GLUT4 “stored”in vesicles as [insulin]¯, endocytosis removes GLUT4 budding fusion endo-some produce intracellularinsulin effects Lehninger et al.,3rd ed., p. 414 19

  23. Fate of nutrients: other cells • dietary triglycerides & cholesterol VLDL,chylomicron TGchol TG glucose↓glycerol-P LIPOPROTEINLIPASE FA FA capillary lumen↑ by insulin glycerol VLDL,chylomicronremnants TGchol fuel adipocytes, others receptor FA, cholesterol liver 14

  24. Postabsorptive (fasting) state • starts when hyperglycemia, hyperlipemia & hyperaminoacidemia are over Fuels available (70-kg person) fuelkg kcal glycogen 0.4 1600 protein 6 24,000 triglycerides 15 135,000 total 161,000 • despite the abundance of fat, the other more versatile and scarcer fuels are also consumed during fasting Fuel versatility amino acids↓↑* ↓ glucose→ fatty acids *C-skeletons of nonessential amino acids 15

  25. Fasting: control of fuel use short-term • most cells mainly use fatty acids & ketone bodies • source lipolysis in adipocytes stimulated by glucagon & epinephrine • brain major exception; requires glucose • sources liver glycogen (~60 g/day) protein (~75 g/day) stimulated by glucagon (liver) & cortisol (muscle) 16

  26. Fasting: control of fuel use • liver main fuel processor converts • glycerol, lactate & amino acids via gluconeogenesis to glucose • fatty acids to ketone bodies long-term fasting • after many days, brain adapts to using ketone bodies (kb) induction of – proteins for kb uptake– enzymes for kb metabolism eventually kb supply ~½ brain's energy needs • result: protein consumption decreases from ~75 g/day to ~20 g/day 17

  27. Distribution of absorbed nutrients • alternating statesabsorptive (feeding) postabsorptive (fasting) • absorptive statehyperglycemia, hyperlipemia, hyperaminoacidemia • events or functions during absorptive state • supply fuel for immediate need • replenish proteins • restore glycogen consumed • storage of excess nutrients as fat 18

  28. Next :4. Major nutrients

More Related