transmembrane domain

cleavage releases enx from cell to act in another part of body

prodomain

where zymogen is cleaved to activate enz

6 enzyme types

oxidoreductase--transfer H or O (redox rxns)

transferase--transfer a spec grp

hydrolase--hydrolysis

isomerase--change molec form

lyase--remove/add grp (not hydrolysis)

ligase--join 2 molec C--O/S/N

TO HILL

Rlshp btw specificity and catalysis

Weak spec-->weaker substrate binding-->inferior catalysis, but can act on many types

Strong spec-->strong substrate binding-->fast, but acts on only a few molecules

Enz activity regulated by: (4)

1. substrate availability

2. enz availability

3. enz activation

4. enz inhibition

Aβ plaques in Alzheimers

Aβ region of APP (transmemb protein) normally cleaved by alpha secretase

in Alzheimer's, genetic mutation makes APP a better substrate for BETA-secretase

results in cleavage at different site by BACE1, then by gamma secretase

releases Aβ, polymerization, plaques, degeneration

alpha, beta, and gamma secretase

act on APP in brain

alpha cleavage: normal

beta, then gamma: Alzheimer's (amyloid plaques)

Cox enzymes

Cox-1: constitutional in GI mucosa

Cox-2 (valine instead of isoleucine @523): inflammatory response

NSAIDs

inhibit Cox 1 & 2

anti-inflammatory, cause GI side effects

trypsin

trypsinogen(zymogen) produced in pancreas, activated in bowel by enterokinase-->trypsin

trypsin activated in pancreas= acute pancreatitis (alcoholism)

protease types (4)

serine

aspartyl

metallo-

cysteine

proteases and connective tissue remodeling (3 pathways)

physiological: growth/development (ex: endochondral ossification)

pathological: ex: arthritis

cancer: proteases are used to invade tissues (metastasis)

metalloproteases: def and 3 types

use metal (Zn) to coordinate hydrolysis

MMP

ADAM

ADAMTS****(N=20)

ADAM TS 2 mutation

disorganized collagen fibers

Ehlers-Danlos syndrome

ADAM TS 4/5 mutation

cartilage breakdown-->arthritis

α2-macroglobulin

protease inhibitor--when enz cleaves bait region, protein snaps shut and traps enzyme, essentially inactivating it

Sulfa drugs

antibiotics

non-mammalian enz=fewer side effects

sulfanamide

antibiotic/sulfa drug/protease inhibitor that inhibits p-aminobenzoic acid, therefore inhibiting folic acid production

Coprine

inky cap mushroom toxin, irreversible covalent bond w alcohol dehydrogenase

when taken w alcohol, acetaldehyde (from ethanol oxidation) accumulates-->sick

t-PA

tissue plasminogen activator-->plasmin-->cleaves fibrin (which is insoluble) in blood clots

indicated post MI