Carbohydrate Protein and Lipid Digestion

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DIGESTION, ABSORPTION AND TRANSPORT OF CARBOHYDRATES

Carbohydrates / Carbs / CHO = 60-70% of diet


Sources:
Starch - polysaccharide Disaccharides sucrose (fructose (F) + glucose(G)),
Cellulose dietary fiber lactose
Monosaccharides fructose, glucose

Sugar Maltose Maltotriose Isomaltose Limit Dextrin Trehalose


Linkage 2G 1,4 3G 1,4 2G 1,6 3-8G 1,4 & 1,6 branching 2G 1,1

I. DIGESTION
Glycosidases cleave / linkages between sugar units via hydrolysis
Specific for type of sugar, linkage type ( or ), and # of units

Phase Cleaves Produces Location Notes


maltose, maltotriose, dextrin, glucose Saliva = 1L/day; mucin (disperses
ORAL PHASE (by random endoglycosidic mouth polysacchs) + amylase; Ca&Cl cofactors,
amylase) optimum pH = 6.6-6.8 (mouth pH = 6)
stomach pH = 2 (very acidic) = amylase
GASTRIC PHASE Minimal acid hydrolysis stomach
denatured
LUMINAL I maltose, isomaltose, limit dextrins,
duodenum bicarbs reduce acidity, contains amylase
(Pancreatic Exocrine) glucose
LUMINAL II

Sucrase- sucrose, isomaltose, maltase glucose,


jejunum
Isomaltase (80% total digestion), maltotriose fructose

oligosaccharides (dextrinase), exoglycosidases (cleaves non-reducing


Glucoamylase maltase (20% total digestion)
glucose ileum
units)
GLYCOSIDIC (in Int. brush
COMPLEXES border )

Lactase/- glucose, 27-32 wks = activity,


lactose jejunum
galactosidase galactose >7 yrs = activity

trehalose (mushrooms, fungi, insects;


Trehalase 2G 1,1)
glucose

DIETARY FIBERS
vegetables, fruits as cellulose, hemicellulose, pectins, mucilages, gums, lignin
not enzymatically digested, no 1,4 glycosidase
intestinal bacteria metabolized in large intestine = CO2, methane (CH4), H2O flatulence
bacterial fermentation acetate, proprionate, butyrate

II. ABSORPTION and TRANSPORT


A. Simple Passive Diffusion pentoses (xylose, arabinose), very little for glucose
B. Facilitated Diffusion fructose, mannose, glucose; forms intermediate complex with specific carrier protein
C. Active Transport glucose and galactose; coupled with Na-K ATPase pump
D. Inhibitors
1. ouabain cardiac glycoside, inhibits Na-K ATPase pump
2. phlorizin plant glycoside, blocks luminal transport
3. cytochalazin inhibits serosal glucose carrier at contraluminal (GLUT2) side
E. Glucose Transporters
Insulin dependent skeletal muscle, adipose tissue
Insulin independent intestinal mucosa, liver, RBC, brain

GLUT Mechanism Function Location


1&3 Na-glucose symport Basal glucose uptake (Km = 1mM) All tissues, intestinal lumen
5 With Na-glucose transport intestinal lumen
glucose Km (15-20mM), allows entry to liver at high glucose liver and pancreas,
2 levels only, pancreas adjusts insulin secretion intestinal serosa
4 transporters due to insulin Muscle and adipose

III. DISEASES
A. -galactosidase (lactase) deficiency lactose intolerance, different from lactoglobulin intolerance (milk protein)
B. Sucrase (Sucrase-Isomaltase Complex) deficiency inherited lack of sucrase and isomaltase, chronic diarrhea, abdominal
pain, low stool pH (lactic acid)
C. Disacchariduria - urinary excretion of disaccharides 300 mg
D. Monosaccharide malabsorption autosomal recessive, congenital, defect in glucose/galactose carrier,
severe diarrhea, abdominal distention
DIGESTION AND TRANSPORT OF LIPIDS

Triacylglycerol (TAG) major fat in diet (>90%), 60-150g/day, major storage lipid, glycerol backbone + 3 fatty acid (FA) esterified
Lingual and Gastric lipases prefers short and medium chain FA ( 12); most active in infants and milk-drinking children; lipid
digestion begins in stomach
Problem: lipids are insoluble in water but enzymes are aqueous; fat initially forms droplets but aggregate = surface area
Solution: emulsify fat to surface area available for lipase action

PHASES
Fat Emulsification in intestine
o By bile salts amphipathic, synthesized in liver, secreted by gallbladder (stimulated by CCK), pKa 6, inhibitory to
pancreatic lipase
act as detergents, binding to globules of dietary fat
TAG hydrolysis = free fatty acid (FFA) + monoacylglycerol (MAG)
o Pancreatic secretions
Pancreatic Lipase major enzyme for TAG digestion, hydrolyzes position 1 and 3 = 2-MAG + 2 FFA
Colipase binds to dietary fat and lipase = makes pancreatic lipase more effective
Bicarbonate raises pH = optimal for intestinal enzymes
Esterases removes fatty acids from compounds (cholesterol esters)
Phospholipases (Phospholipase A2) digests phospholipids
Solubilization by detergents (bile acids/salts); transport to cell
o FFA, 2MAG packaged into micelles (tiny droplets emulsified by bile salts)
o Other fats (cholesterol, fat-soluble vitamins) also packaged in micelles
o Bile salts need to overcome a certain concentration to form micelles = 5-15 mol/mL
o Micelles travel through the unstirred layer of water to the microvilli on the surface of intestinal epithelial cells and
absorbed via simple diffusion
o Bile salts remain in gut, resorbed in ileum; 95% recirculated, only 5% loss
o Short and medium chain FA do not require bile salts, absorbed directly, enter portal blood directly without packaging
Uptake of FFA and MAG into intestinal cell; Resynthesis to TAGS
o Within intestinal cell: 2 FFA + 2-MAG TAG via CoA and CoASH in SER
Packaging of TAGs into chylomicrons
o Chylomicrons contains TAGs to prevent coalescing in blood, brings TAGs to lymphatics; made up of lipoproteins; may
contain cholesterol and fat-soluble vitamins
o Amphipathic, hydrophobic interior, with cholesterol OH group near surface
o Hydroxyl group esterified to FA in the interior in cholesterol esters
o major lipoprotein B-48
Transport in blood
o Chylomicron exocytosis chyle of lymphatics thoracic duct
o Chylomicrons enter blood 1-2 hours after start of meal
DIGESTION OF PROTEINS
Protein (CHON) AA via hydrolysis Daily CHON Load: 70-100 g (dietary); 35-200g (endogenous) Very efficient digestion in humans

FUNCTIONS
Building and maintaining body tissues Formation of enzymes, hormones, fluids, secretions Acid-base balance of blood and tissues
Source of energy (4 kcal/g) Maintaining normal osmotic relations Transport of various substances

DIGESTIVE ENZYMES
Enzymes secreted in zymogen form inactive precursors of digestive enzymes activated by cleavage of peptide chains
CHON digestive enzymes are peptidases (a type of hydrolase) that cleave peptide bonds
o Endopeptidase attack internal bonds liberating large peptide fragments
o Exopeptidase cleaves off one AA at a time from the terminals

Site of Fragment Cleaved for Means of


Enzyme Zymogen Activation Specificity Notes
activation
GASTRIC PHASE
Optimum pH 1.5-2.5; Gastric juice (HCl) lowers pH, kills microorganisms, denatures proteins
produces large peptides and some free AA stimulate CCK release initiate pancreatic phase
Pepsin Pepsinogen 42-44 AA HCl, pepsin peptide bonds with C-group from From chief cells of stomach, acidity enables pepsinogen to autoactivate, product
aromatics and acidics ( Phe, Tyr, (large peptides) stimulate CCK release to initiate pancreatic phase
Glu, Asp)
Rennin ? ? ?
PANCREATIC PHASE
Optimum pH 7.5-8.5; Bicarbonate rich = pH, produces: shorter oligopeptides, free AA
Trypsinogen Hexapeptide Enterokinase, peptide bonds with C-group from Endopeptidase
Trypsin
trypsin basic AA (arg, lys)
Chymotrypsinogen 2 dipeptides, creating Trypsin peptide bonds with C-group from Endopeptidase
Chymotrypsin
a 3 subunit enzyme aromatics, leu, met
Proelastase Decapeptide? Trypsin peptide bonds with C-group from Endopeptidase
Elastase
small AA (ala, gly, ser)
Procarbopeptidase A 2 large fragments Trypsin N-side of C-terminal AA Exopeptidase
Carbopeptidase A Aliphatic / hydrophobic val, leu,
ile, ala
Procarbopeptidase B ? Trypsin N-side of C-terminal AA Exopeptidase
Carbopeptidase B
Basic AA (arg, lys)
INTESTINAL PHASE
Optimum pH 7.5-8.5, from luminal surface of epithelial cells, produces free AAs
Aminopeptidase ? ? ? Exopeptidase
Di/tripeptidase ? ? ? Dipeptides Endopeptidase
Tripepditase ? ? ? Tripeptides Endopeptidase

ABSORPTION and TRANSPORT


Location Type of Transport Notes
Na+ dependent co-transport Same as sugars; semi-specifig, driven by intraceullar Na+ due to Na-K-ATPase on serosa; overlapping specificity for different AA
Facilitated diffusion to concentration
Lumen to Intestinal Cell
-glutamyl cycle AA passes membrane through -glutamyl transpeptidase Glutathione (Glu,Cys,Gly) + AA cysteinylglycine -glutamylAA AA + 5-
Oxoproline Glutamate + Cysteine -glutamylcysteine + glycine Glutathione
Intestinal Cell to Plasma Facilitated transport In vivo: intestinal cell AA conc > blood; during starvation: AA conc in blood > cell = bidirectional transport
Facilitated diffusion Lesser extent
Plasma to Other cells
Na+ dependent co-transport Liver / muscle conc AA from blood

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