Lecture 3: Digestion

hydrolases

cleave substrates by addition of water molecule

proteases, a-amylase, lipases, nucleases

protein digestion origin

stomach by HCl and pepsin

protein digestion major site

small intestine

parietal cells

secrete HCl

gastric chief cells

secrete pepsin

pancreatic enzymes

intestinal lumen, polypeptides → oligopeptides

brush border enzymes

intestinal epithelial surface, peptidases, oligopeptides → AAs

portal circulation

absorbed AAs enter blood and travel to liver

final protein digestion/absorption site

brush border of SI

HCl functions

protein denaturation, pepsinogen → pepsin

pepsin positive feedback

small amount of low pH pepsin activates additional pepsinogen

what activates pancreatic enzymes?

enteropeptidase and proteases

enteropeptidase

converts trypsinogen → trypsin to also convert chymotrypsin, elastase, and carboxypeptidase

CCK

hormone that causes release of enteropeptidase

zymogens

inactive proenzymes

endopeptidases

trypsin, chymotrypsin, elastase

exopeptidases

carboxypeptidase

AA transport from intestinal lumen → epithelial cells

NA+ dependent co-transport

AA transport from epithelial cells → blood

facilitated transporter

cysteine vs cystine

cystine is oxidized, dimeric form linked by disulfide bond

Hartnup disease

tryptophan deficiency due to defective absorption of neutral AAs

Cystinuria

disorder of reabsorption of dibasic AAs and cystine → cystine stones in urinary tract

where does carb digestion start?

in the mouth via salivary a-amylase

a-amylase

breaks down a-1,4-glycosidic bond

a-Glucosidase

hydrolyzes a-1,4 bonds

a-Dextrinase

hydrolyzes a-1,6 bonds

a vs B-glucose

a - hydroxyl group and CH2OH at C-5 on opposite sides

SGLT1

transports glucose and galactose from lumen → enterocyte

GLUT5

transports fructose from lumen → enterocyte

GLUT2

transports enterocyte monosaccharides into bloodstream

lactose intolerance

lactose broken down into osmotically active 2- and 3-carbon metabolites

stomach lipid digestion enzymes

lingual and gastric lipase

lipase is most active in which age group?

infants and kids who drink cows’ milk

emulsification

increases surface area of hydrophobic lipid droplets

where does lipid emulsification occur?

duodenum

lipid digestion end products

free FAs and 2-monoacylglycerol

micelles

drops surrounded by bile salts

do short and medium chain FAs require micelles for absorption?

no

do bile salts stay in the lumen?

yes

chylomicrons

transport lipids from SI, assembled in Golgi

chylomicrons components

apo B-48, phospholipids, free cholesterol surround TAGs and cholesterol esters

chylomicrons secretion

by exocytosis into lymphatic vessels

ApoCII

activates lipoprotein lipase to degrade chylomicron TAG

ApoE

recognized by hepatic receptors to remove chylomicron remnants from liver

nascent chylomicron

chylomicron without ApoCII or ApoE

where do chylomicrons get ApoCII and ApoE from?

HDL (high density lipoprotein)

what returns from the chylomicron to the HDL after lipids transported?

ApoCII

low pH stimulates…

SI to release secretin

secretin stimulates…

pancreas bicarbonate secretion to neutralize stomach acid

CKK release stimulated by…

polypeptide products of pepsin digestion and digested lipids

CKK causes secretion of…

1. gall bladder bile salts

2. pancreas digestive enzymes

3. intestinal epithelial cells enteropeptidase

steatorrhea

presence of excess fat in feces due to poor digestion and malabsorption

cystic fibrosis lipid malabsorption

causes decreased hydration

where does nucleic acid digestion begin?

in the stomach via denaturing from low pH

ribonucleases and deoxyribonucleases

pancreatic enzymes, DNA/RNA → oligonucleotides

phosphodiesterase

pancreatic enzyme, oligonucleotides → mononucleotides

nucleotidases

remove phosphate groups of mononucleotides in intestinal mucosal cells

nucleosidases

nucleosides → pyrimidine and purine

purine and pyrimidine digestion fate

purine → uric acid, pyrimidines enter circulation for reuse