Block 2 Lecture 1 -- Digestion & Absorption Flashcards
essential AAs
1) Phe
2) Val
3) Try
4) Thr
5) Ile
6) Met
7) His
8) (arg)
9) Leu
10) Lys
**Arg for growth
2 families of pancreatic enzymes
1) exopeptidases
2) endopeptidases
characterize the exopeptidases
1) aminopeptidases cleave from N-terminus
2) carboxypeptidases cleave from C-terminus—–A after hydrophobes—–B after basic
How do exopeptidases work?
cleave from a terminal end one AA at a time
What are examples of pancreatic peptidases?
1) trypsin
2) chymotrypsin
3) elastase
Function of trypsin
– most specific endopeptidase– after Lys or Arg
Function of chymotrypsin
cleaves after hydrophobic AAs– Phe, Tyr, Trp, Leu
Function of elastase
cleaves AAs with small side chains– Ala, Gly, Ser
What conditions yield a negative N Balance?
starvation, disease, 1 essential AA deficiency
What conditions yield a positive N balance?
growth
pregnancy
illness recovery
re-feeding post-starvation
inorganic sources of N
N2
NO2
NO3
pathophysiology of kwashiorkor
protein deficiency –> decreased albumin –> edema
pathophysiology of acute pancreatitis
gall stones, EtoH– ducts blocked, enzymes attack self
pathophysiology of whipple’s dz
Tropheryma whippelii infects SI to cause malabsorption– diarrhea, GI bleeding, abdominal pain
Treatment for kwashiorkor
re-feed pt slowly since pts lose ability to digest
What AAs make up gluten?
15% Pro, 30% Gln
Where is gluten found?
wheat, barley, rye, oats
Pathophys of celiac dz
1) Gln deamidated by transglutaminase
2) Product binds to APC
3) Peptide-DQ2 triggers Th1 proliferation in gut mucosa
4) villi damage due to immune reaction
Treatment for celiac dz
avoid gluten
pathophys of cystinuria
1) transport defect for cysteine & basic AAs (Lys, Arg, Ornithine)
2) cysteine oxidized in blood –> cystine
3) kidney stones….this is a genetic dz
Tx for Hartnup dz
niacin (b3) + hi-protein diet
Pathophys of hartnup dz
….genetic dz……
1) neutral AA transport defect in intestine & kidney—essentials = Ile, Leu, Phe, Thr, Trp, Val
2) NAD deficiency (derived from Trp)
3) hyperaminoaciduria, photosensitivity rash, ataxia
How are amino acids degraded?
1) 30% via lysosomal degradation
2) 70% via ubiquitin-proteasome
how is polyubiquination accomplished?
26S = 20S + 1/2 19S caps
1) 19S binds (reqs ATP)
2) 20S unfolds protein (req’s ATP)
3) generates small peptides
Asp TA pair
OAA
Ala TA pair
pyruvate
Glu TA pair
alpha-KG
Which AAs do not have TA pairs?
1) Lys
2) Thr
3) Pro
Where is ALT / GPT found?
hepatocytoplasm
Where is AST / GOT found?
hepato, cardio, & myocytes
What does ALT/GPT stand for?
Ala TA
glutamic pyruvic TA
What does AST / GOT stand for?
Asp TA
glutamic oxaloacetic TA
How is trypsin activated?
enteropeptidase (brush border)
What enzymes involved in protein digestion are pancreatic?
1) chymotrypsinogen2) proelastase
3) procarboxypeptidases
4) trypsinogen
How does pepsin cooperate with pancreatic enzymes?
= trypsin inhibitorpepsin inactivated by HCO3-
Where do peptidases “cut” peptides?
after the carbonyl of the specified AA
What elements are required for the gamma-glutamyl cycle?
1) ATP
2) covalent linkage
3) GGT
4) Glutathione (GSH)
Glutathione is otherwise known as:
gamma-glutamyl-cysteinyl-glycine
Describe the reaction catalyzed by 5-oxoprolinase.
g-Glutamyl-AA –> 5-oxoproline + AA
Where is ATP required in the gamma-glutamyl cycle?
1) 5-oxoproline –> Glu
2) Glu + Cys –> gamma-glutamyl-cysteine
3) gamma-glu-cys –> GSH
What transporters transport AA into cells?
1) primarily Na-dependent co-transporters
2) also facilitated diffusion transporters
3) GI transporters are genetically & specifically different
How do AA transporters differ from glucose transporters?
AA transporters are primarily Na-dependent in all locations.Glucose transporters are Na-dependent only in liver/kidney
Describe the AA transporters in an intestinal epithelial cell.
1) luminal side = 6 Na-dependent co-transporters OR GGT
2) basal side = facilitated transporters
Where does the gamma-glutamyl cycle take place?
intestine & kidney
What are the products of lysosomal degradation?
1) FREE AAs
2) Glucose
3) FAs
What diseases cause excessive protein degradation via the lysosomal pathway?
cancer, RA
How many proteasomes in a single cell?
~ 30,000
What is the rate of polyubiquination in resting vs. dividing cells?
1) resting = 5 * 10^5 proteins/min
2) dividing = 2 * 10^6 proteins/min
What are the mechanisms of protein degradation?
1) poly-ubiquination
2) lysosomal degradation
What is the product of the ubiquitin-proteasome pathway?
small peptides 8-11 AAs in length
What diseases cause excessive protein degradation via polyubiquination?
1) cancer
2) RA
3) other autoimmune diseases
What drugs target the 26S proteasome?
Carfilzomib, Bortezomib
