Transcript Digestion & absorption of carbs & proteins

Section 10
Nutrients & Their Functions
1. Acquiring nutrients
Digestion & absorption
of
carbohydrates & proteins
1/3/06
Section 10
Acquiring 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
O
O
 chemical reaction: hydrolysis

H2O + RX –YR'  RXOH + HYR'
where X = C, P Y = O, N
 reaction catalyzed by hydrolases
major nutrients
hydrolase type
poly, oligosaccharides
glycosidase
proteins, peptides
protease, peptidase
fats (triglycerides)
esterase
minor nutrients
O
H 2O
O
O
OH
HO
bond cleaved
glycosidic
peptide
ester
phospholipids, nucleic acids phospholipase, nuclease phosphoester
esters (e.g., cholesterol, retinol) esterases
ester
2
Activation of hydrolases

noncovalent
activator binds reversibly to enzyme
examples: enzyme
activator
a-amylase Cl –
lipase
colipase

covalent
activator catalyzes hydrolysis of one or more peptide bonds
of precursor
activator
precursor  active enzyme
(proenzyme or zymogen)
examples:
3
HCl
pepsinogen  pepsin
trypsin
proelastase  elastase
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)
amylopectin:
products: maltose, maltotriose
*
a1,6 linkage
* indicates
typical
a-amylase
hydrolysis site
*
*
*
*
products:
4
maltotriose (glc3)
an a-limit dextrin
maltose
Carbohydrates: digestion (oligo mono)

Stage II: oligosaccharides  monosaccharides
source of enzymes: mucosal cell surface (brush border)
a-limit dextrins
maltose
glc3
sucrose
lactose
5
isomaltase
(a-dextrinase)
α1,6 glucosidic bonds
 2 glc
maltase
 3 glc
"
 glc + fructose sucrase
 glc + gal
lactase (inducible)

glc3 + glc
+ maltose
a-limit dextrins: (glc)4-9 with one a1,6 linkage
glc: glucose gal: galactose
Carbohydrates: absorption from lumen
 frc
& mannose
facilitated diffusion
(carrier-mediated)
 glc & gal
transported against
concentration gradient
+
 cotransport (Na
gradient-driven
symport)
 aka secondary
active transport

 pentoses,
6
others
absorbed via
simple diffusion
Na+ glc
symport
protein
glc-Na+ symport
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7
glc-Na+
symport
protein
+
glc-Na symport
mechanism
1. outer gate open,
sites unoccupied
2. sites occupied,
outer gate closing
3. inner gate opening
4. Na+, glc
dissociating
5. inner gate closed,
outer gate opening
glc-Na+
symport
protein
lumen of
small
intestine
Glucose movement:
lumen  blood
 transport
into mucosal cell
(enterocyte)
mucosal
cell
across luminal (apical)
membrane
 against concn. gradient
+
 Na glc symport

 transport
glucose
(lower conc.)
Na+
glucose
(higher conc.)
out of mucosal cell
across contraluminal
(basolateral) membrane
 down concn. gradient
 glc transporter (GLUT2)
+ glc
Na
Na+ transporter
(symport)
Na+
K+

8
GLUT2
glucose carrier
(facil. diffusion)
Na+,K+
ATPase
glucose
(lower conc.)
K+
Na+
interstitial fluid
blood
Proteins: digestion to peptides & amino acids
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







9
denatures (unfolds) proteins
solubilizes iron, other metals (ions)
inactivates pathogenic organisms (antiseptic)
stimulates secretion of secretin & cholecystokinin (CCK)
activates pepsinogen
in bulimia, erodes enamel
Proteins: gastric digestion
 peptidases
(proteases, proteolytic enzymes)
exopeptidases: peptide bonds next to N- or C-terminus
 endopeptidases: bonds not next to N- or C-terminus

 pepsin
O
O
O
O
H3NCC–NCC–NCC–NCC–NCCOO–
exo endo endo exo
+
endopeptidase
 secreted as pepsinogen by chief cells (stimulus: gastrin)
 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
10
Gastric secretions
& digestion
HCl secretion
by parietal cells
 pepsinogen secretion
by chief cells
 pepsinogen activation by



HCl
pepsin
autocatalysis: product
activation of precursor
pepsinogen
360
42
pepsin
11
HCl,
pepsin
Sherwood, Fig. 16-11
Proteins: intestinal secretions & digestion
HCl, peptides
in chyme stimulate duodenum to 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)

12
* aka enterokinase
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
carboxypeptidase A
exo
"
nonpolar, aromatic
" B
"
"
cationic
 mucosal cell luminal surface peptidases



13
aminopeptidase (peptide bond next to N-terminus)
dipeptidase (dipeptides)
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


14
within a class, substrate specificity due to structure
of part of the active site: the specificity site
Serine proteases: specificity pocket

binding pocket structured to favor side chains on
substrate that are:



nonpolar/aromatic chymotrypsin
cationic
trypsin
small
elastase
gly
226
gly
226
ser
189
15
N
gly
216
chymotrypsin
N
+
–
N
gly
216
thr
216
val
226
asp
189
trypsin
elastase
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
 analogous
to glc
movement (slide 8)
 absorption via symports
lumen of
small
intestine
Na+
amino acids
small H+
peptides H+ peptide
symport
Na+ aa
symport
mucosal
cell
Na+
aa: Na+ gradient-driven
+
 peptides: H gradient-driven
H+

 in
amino acids
peptidases small
cytosol:
peptides  amino acids
 aa’s cross contraluminal
membrane via facilitated
diffusion carriers
amino acid
peptides
Na+
K+
carriers
(facil. diffusion)
amino acids
18
interstitial fluid
Na+,K+
ATPase
K+
Na+
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