Section 10 Nutrients & Their Functions

Section 10Nutrients & Their Functions 1. Acquiring nutrients Digestion & absorption of carbohydrates & proteins 1/3/06

Section 10Acquiring Nutrients Overview nutrients digestion, absorption glucose, amino acids, fats distribution precursors, available fuels metabolism macromolecules, energy, end products 1

Digestion: general features • general function: convert nutrients into absorbable form • larger molecules (macro)  smaller molecules • chemical reaction: hydrolysis H2O + RX–YR'  RXOH + HYR' where X = C, P Y = O, N • reaction catalyzed by hydrolases major nutrients hydrolase type bond cleavedpoly, oligosaccharides glycosidase glycosidic proteins, peptides protease, peptidase peptidefats (triglycerides) esterase ester minor nutrients phospholipids, nucleic acids phospholipase, nuclease phosphoester esters (e.g., cholesterol, retinol) esterases ester H2O 2

Activation of hydrolases • noncovalentactivator binds reversibly to enzyme examples: enzyme activatora-amylase Cl– lipase colipase • covalentactivator catalyzes hydrolysis of one or more peptide bonds of precursor activator precursor  active enzyme(proenzyme or zymogen) HClexamples: pepsinogen  pepsin trypsin proelastase  elastase 3

Carbohydrates: digestion (polyoligo) • only monosaccharides are absorbable • Stage I: polysaccharides  oligosaccharides • enzyme:a-amylase (specificity: internal a1,4 glucosidic bonds) sources: salivary glands (minor) & pancreas (major) • substrates: amylose (only a1,4 links) products: maltose, maltotriose 4 (glc3)

Carbohydrates: digestion (oligomono) • Stage II: oligosaccharides monosaccharides sourceof enzymes: mucosal cell surface (brush border) a-limit dextrins  glc3 + glc isomaltase+ maltose (a-dextrinase)α1,6 glucosidic bonds maltose  2 glc maltase glc3  3 glc " sucrose  glc + fructose sucrase lactose  glc + gal lactase (inducible) a-limit dextrins: (glc)4-9with one a1,6 linkage glc: glucose gal: galactose 5

Carbohydrates: absorption from lumen • frc & mannose facilitated diffusion (carrier-mediated) • glc & gal • transported againstconcentration gradient • cotransport (Na+ gradient-driven symport) • aka secondaryactive transport • pentoses, othersabsorbed via simple diffusion Na+ glc symportprotein 6

glc-Na+ symport animation • for “snapshots” of this animation, see the next slide • stop animation by clicking browser’s Stop button • resume animation by going to another slide, then return-ing to this one glc-Na+ symportprotein 7

glc-Na+ symportmechanism glc-Na+ symportprotein • outer gate open, sites unoccupied • sites occupied, outer gate closing • inner gate opening • Na+, glc dissociating • inner gate closed, outer gate opening 7

Glucose movement: lumen  blood lumen of small intestine Na+ glctransporter(symport) glucose(lower conc.) Na+ • transport into mucosal cell(enterocyte) • across luminal (apical) membrane • against concn. gradient • Na+glc symport • transport out of mucosal cell • across contraluminal (basolateral) membrane • down concn. gradient • glc transporter (GLUT2) mucosalcell Na+ glucose(higher conc.) Na+ K+ GLUT2glucose carrier(facil. diffusion) Na+,K+ATPase K+ glucose(lower conc.) Na+ 8 interstitial fluid blood

Proteins:digestiontopeptides &aminoacids • only amino acids & some small peptides absorbable • stomach: food polypeptides stimulate G-cells in pyloric region to secrete the hormone gastrin • gastrin stimulates parietal cells to secrete HCl • effects of HCl • denatures (unfolds) proteins • solubilizes iron, other metals (ions) • inactivates pathogenic organisms (antiseptic) • stimulates secretion of secretin & cholecystokinin (CCK) • activates pepsinogen • in bulimia, erodes enamel 9

Proteins: gastric digestion • peptidases (proteases, proteolytic enzymes) • exopeptidases: peptide bonds next to N- or C-terminus • endopeptidases: bonds notnext to N- or C-terminus • pepsin • endopeptidase • secreted as pepsinogen by chief cells • activation: catalyzed by HCl, pepsin (self-activation) • specificity: bonds next to aromatic side chains (phe, tyr, trp) • an aspartate protease (2 asp at active site; slide 14) • main result of passage through stomach: polypeptides unfolded & converted to large peptides +O O O O H3NCC–NCC–NCC–NCC–NCCOO–exo endo endo exo (stimulus: gastrin) 10

Gastric secretions & digestion • HCl secretion by parietal cells • pepsinogen secretionby chief cells • pepsinogen activation by • HCl • pepsinautocatalysis: product activation of precursor Shrwd5_16-11.jpg pepsinogen 360 42 pepsin HCl,pepsin 11 Sherwood, Fig. 16-11

Proteins: intestinal secretions & digestion • HCl,peptides in chyme stimulate duodenumto secrete • CCK: stimulates pancreas to secrete enzyme-rich juice • secretin: stimulates pancreas to secrete HCO3–-rich juice • gastric inhibitory peptide: inhibits antral contractions • HCO3– raises pH of chyme to 7-8 • pancreatic proteases: trypsin (an endopeptidase) • secreted as trypsinogen • trypsinogen activated by enteropeptidase* (mucosal cells) & by trypsin (self-activation) • important as activator of many other digestive enzymes • specificity: bonds next to cationic side chains (lys, arg) • a serine protease (contains a catalytic triad; slide 14) *aka enterokinase 12

Intestinal digestion by peptidases • pancreas also secretes trypsin inhibitor • other pancreatic peptidases peptidase type activator side chain specificity chymotrypsin endo trypsin nonpolar, aromatic elastase " " small, aliphatic carboxypep-tidase A exo " nonpolar, aromatic " B " " cationic • mucosal cell luminal surface peptidases • aminopeptidase (peptide bond next to N-terminus) • dipeptidase (dipeptides) 13

Protease classes or families • all proteases belong to 1 of 4 classes • classification based on main catalytic site feature protease class examples serine (section 4) trypsin, chymotrypsin, elastase, thrombin, plasmin zinc " carboxypeptidases, thermolysin thiol (cysteine) papain, cathepsins (lysosomes) aspartate pepsin, renin, HIV-1 protease • within a class, substrate specificity due to structure of part of the active site: the specificity site 14

Serine proteases: specificity pocket • binding pocket structured to favor side chains on substrate that are: • nonpolar/aromatic chymotrypsin • cationic trypsin • small elastase N gly216 thr216 gly216 N gly226 N +– gly226 val226 asp189 ser189 chymotrypsin elastase trypsin 15

Absorption of peptides & amino acids from GI lumen • amino acids • Na+ gradient-driven symports (cotransport) mechanism same as glucose–Na+ symport • at least 6 kinds of symport proteins • specificities by amino acid types examples: small, polar side chains (ala, ser, thr) cationic side chains (lys, arg) anionic side chains (asp, glu) 16

Absorption of peptides & amino acids • some small peptides are absorbed • mostly di- & tripeptides • H+ gradient-driven symport • absorbed peptides hydrolyzed to amino acids by cytosolic peptidases • amino acids reach portal blood via facilitated diffusion across contraluminal membrane of mucosal cells • mechanism same as monosaccharide systems • specific transmembrane carrier proteins 17

Amino acids, peptides movement: lumen ® blood lumen of small intestine H+ smallpeptides Na+ • analogous to glcmovement (slide 8) • absorption via symports • aa: Na+ gradient-driven • peptides: H+ gradient-driven • in cytosol: peptides ® amino acids • aa’s cross contraluminalmembrane via facilitateddiffusion carriers H+ peptidesymport amino acids Na+ aasymport mucosalcell H+ Na+ peptidases smallpeptides amino acids Na+ K+ Na+,K+ATPase amino acid carriers(facil. diffusion) K+ amino acids Na+ 18 interstitial fluid blood

Study questions • Describe step-by-step the processes of digestion, absorption, and distribution of proteins. Include the roles of enzymes, activators, hormones, and membrane transport. • Do the same for carbohydrates.

Next time:Digestion & absorption of lipids

Section 10 Nutrients & Their Functions