Digestion of Proteins and Amino Acids Ezinne Akudinobi John Butler Hannah Casey Lim Melody Adeuyan Physiology 3 November 14, 2016

Review: Amino Acids 400-plus naturally occurring amino acids 20 standard set of amino acids 9 essential amino acids Obtained through diet Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine 4 nonessential amino acids Produced in the body Alanine, asparagine, aspartic acid and glutamic acid 7 conditional amino acids Needed in times of illness and stress Arginine, cysteine, glutamine,glycine, proline, serine and tyrosine http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Graphics/ChemBasicLabelled.gif

Review : Protein Structure http://virtuallaboratory.colorado.edu/BioFun-Support/AllGraphics/peptideBond.gif

Metabolism "Connections of carbohydrate, protein, and lipid metabolic pathways," Mikael Häggström

Function of Proteins Antibodies Enzymes Messengers Receptors Structural Components Transport and Storage ©www.sigma-aldrich.com

Digestion: Mouth to Stomach Mechanical digestion begins in the mouth Trigeminal Nerve (Mandibular Division) innervates muscles of mastication Teeth cut and grind proteins into smaller components Saliva lubricates and binds food to form a bolus Bolus travels through the esophagus to the stomach http://digestionsystem.weebly.com/mouth.html

Stomach Pepsinogen from chief cells HCl from parietal cells Histamine from enterochromaffin-like cells → promote HCl release from parietal cells Gastrin from G cells → promote HCl release from parietal cells Somatostatin from D cells → inhibits parietal cells, chief cells and enterochromaffin-like cells to slow the HCl release pathway With all these chemicals, how does it all work? What does physiology have to do with it? Stomach

Formation of hydrochloric acid in stomach Remember that parietal cells secrete HCl. How? Enterochromaffin-like cell releases histamine ← ← ← requires ATP Proton-potassium pump HCl Bicarbonate-chloride pump High [Cl-] Low [K+] High [K+] G cell releases gastrin to blood Low [Cl-]

Parasympathetic: rest and digest Vagus Nerve releases ACh. ACh receptors on parietal cells and enterochromaffin-like cells trigger HCl production in stomach Parasympathetic: rest and digest

X X X Too much HCl in stomach? Enterochromaffin-like cell releases histamine X HCl G cell releases gastrin to blood Too much!!!! X D cells release hormone somatostatin to inhibit all HCl production/promotion pathways

Pepsin to pepsinogen Chief cells Secrete pepsinogen (inactive) which is activated by the HCl of parietal cell HCl Pepsin hydrolyses proteins, breaking them down into peptides ready to enter duodenum...

Protein Digestion: Role of Pancreas •Organ lies medial and superior to duodenum •Both endocrine and exocrine function •Pancreatic juice and bile are secreted into the duodenum through pancreatic duct. •Pancreatic duct (1/16 inch in diameter) joins the common bile duct to empty secretions through duodenal papilla •Release is controlled by sphincter of ampulla

Protein Breakdown Continues •Arrival of chyme into duodenum prompts reflex secretion of pancreatic juice and bile •Stimulated by neural reflexes in duodenum and by secretion of cholecystokinin (CCK) and secretin (hormones in the duodenum) •Secretion of pancreatic enzymes stimulated by ACh released by Vagus nerve and CCK (secreted by duodenum) •Partially digested fat and protein content of chyme stimulate CCK

Exocrine Function: Ductal Cells Secrete a solution rich in bicarbonate into lumen Pancreatic ductal cells put hydrogen ions into blood Neutralizes effect of gastric acid secretion’s alkaline tide

Exocrine Function: Acinar Cells • Common bile duct passes through head of pancreas • Joins pancreatic duct and forms ampulla of Vater • Empties into duodenum • Acinar cells surround lumen of pancreatic duct, which receives contents of secreted pancreatic juice

Exocrine Function: Acinar Cells •Within lobules, exocrine secretory units are called acini (Latin for “berry”) •Each acinus has single layer of acinar epithelial cells •To minimize risk of self-digestion within pancreas, most pancreatic enzymes are produced as inactive molecules called Zymogens. Stored in Zymogen granules.

Key Zymogens Affecting Protein Digestion •Trypsinogen •Chymotrypsinogen •Proelastase •Procarboxypeptidase

Functions of Protein-Specific Zymogens on Activation Endopeptidases: Cleave internal peptide bonds •Trypsinogen to Trypsin (activated by enterokinase) •Chymotrypsinogen to Chymotrypsin (activated by trypsin) •Proelastase to Elastase (activated by trypsin) Exopeptidases: Cleave last amino acid from carboxyl-terminal end of polypeptide •Procarboxypeptidase to Carboxypeptidase (activated by trypsin) •Aminopeptidase (NOT in pancreatic juice, but a brush border enzyme)

Trypsin is key enzyme in pancreatic juice Trypsin is key enzyme in pancreatic juice. Hydrolysis reaction cleaves peptide chains primarily at the carboxyl side of the amino acids lysine and arginine.

Digestion of Polypeptides Free Amino Acids •Absorbed by secondary active transport carriers across brush border membrane Dipeptides and Tripeptides •Enter epithelium by single membrane carrier using a hydrogen gradient •Hydrolyzed into free amino acids •Move across basolateral membrane to interstitial fluid, then capillary blood

Proteins in the Small Intestine Digestion of proteins is completed in the S.I. and mostly occurs in the duodenum Absorption occurs in the jejunum Villi: increase surface area to allow for increased nutrient absorption

Protein Digestion in the Small Intestine Zymogens released by the pancreas begin the process Trypsinogen, Procarboxypeptidase and Chymotrypsinogen Activated by the enzyme Enterokinase on the surface of the S.I. cells Trypsinogen → Trypsin Procarboxypeptidase → Carboxypeptidase Chymotrypsinogen → Chymotrypsin

Protein Digestion in the Small Intestine Trypsin hydrolyzes peptide bonds between the amino acids Trypsin is the most important of the protein-specific Zymogens because it: stimulates the conversion of more Trypsin helps convert Chymotrypsinogen to Chymotrypsin helps convert Procarboxypeptidase to Carboxypeptidase Carboxypeptidase also hydrolyzes peptide bonds Chymotrypsin hydrolyzes peptide bonds at the carboxyl ends After these enzymes do their jobs, the proteins are now smaller polypeptide fragments but digestion in the small intestine is not complete

Brush Border Enzymes Dipeptidases: hydrolyze dipeptides Aminopeptidases: hydrolyze peptide bonds from the amino terminal Break down into tripeptides, dipeptides, and single amino acids Tripeptides → absorbed through a cotransporter with H+ ion into SI cell Intracellular peptidases break it down into amino acids Dipeptides → absorbed through a cotransporter with H+ ion into SI cell Na+ ions antiport into the cell while the H+ ions are pumped back into the lumen

Single Amino Acids Single Amino Acids → absorbed with one Na+ ion into cell Once at the amino acid level, they are transported into the blood capillary to travel the liver Net absorption of Na+ ions causes water to also be absorbed Using the Na+/K+-ATPase pump, sodium is pumped into extracellular matrix in exchange for potassium In the liver, amino acids are stored or used to synthesize new proteins

Questions?

References http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/anatomy.html https://ghr.nlm.nih.gov/about/reviewed-published-dates http://www.sigmaaldrich.com/life-science/biochemicals/biochemical-products.html?TablePage=21735648 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312700/ https://medlineplus.gov/ency/article/002222.htm