K_M=

[s]@v_max/2

concentration of substrate at half of maximal velocity

Large/small K_M means:

large: low affinity of enz for substrate

small: high affinity of enz for substrate

Lineweaver-Burk plot

rearrangement of Michaelis-Menten eqn

displays info as linear, easier to understand

[image]

competitive inhibitor

binds at catalytic site, competes with substrate

reversible

V_max unchanged

reversal of competitive inhibition

raise substrate conc.

ex: CO poisoning treated w 100% oxygen

noncompetitive inhibitor

inhibitor structure unrelated to substrate structure

binds enz at site other than catalytic

K_M unaltered, V_max decreased

ACE inhibitors

angiotensin-converting enzyme inhibitors (competitive)

treatment of hypertension and congestive heart failure

ex: captopril, enalapril, benazepril, quinapril, losartan, valsartan, saralasin

methotrexate

competitively inhibits DHFR (tetrahydrofolate synthesis--folic acid synth, needed for thymidine and purine base synthesis--inhib DNA, RNA, protein, thymidylate synth)

tx of cancer, autoimmune diseases, ectopic pregnancy, med abortions

Aspirin

irreversible inactivation of Cox enzymes

inhibits prostaglandin/thromboxane synth

different from other NSAIDS in that it is not reversible

Poisons and enzyme inhibition

cyanide

CO

PCB (polychlorinated biphenols)

substrate inhibition

results in immediate change in velocity

product inhibition

immediate change in vmax and/or Km

allosteric control

immediate change in vmax and/or K_.5

covalent modification

immediate change in vmax and/or K_M

Synthesis or degradation of enzyme

change in amount of enzyme on order of hours or days

phosphorylation

stimulates or inhibits enzyme activity

glycogen phosphorylase

breaks down glycogen, activation by phosphorylation in response to the binding of epinephrine to a cell surface receptor

location of allosteric enzymes

branch points in metabolic pathways

heterotropic effectors

bind at allosteric sites

homotropic effector

when substrate itself induces allosteric effects when binds to catalytic site

allosteric feedback inhibition and threonine-->isoleucine pathway

when product of metabolic pathway inhibits first enzyme

ex: isoleucine inhibits threonine deaminase

Alanine transaminase (ALT)

Aspartate aminostransferase (AST)

liver enzymes--levels indicate liver health

nonviral liver disease/damage ALT/AST <1

viral hepatitis ALT/AST>1

Lactate dehydrogenase (LDH)

diagnostic for MI

5 types

following MI, LDH serum levels rise within 24-48 hrs, peak by 2-3 days and return to normal in 5-10 days

LDH-1/LDH-2 ratio

normal: <1

following MI: >1 in 12-24 hrs, present within 48 hrs in 80% of patients

Creatine Kinase (CK) aka Creatine Phosphokinase (CPK)

3 types

3--present in skeletal muscle (100% of normal serum CPK)

2--35% of CPK in cardiac muscle (0% of normal serum CPK, rises within 3-6 hrs of MI, peaks 12-24)

1--brain/smooth muscle (0% in normal serum CPK)

rise in CPK-2/total CPK indicative of MI, but rise in CPK in itself is NOT necessarily an indication of MI