quiz 4 chapter 2 Flashcards
are a family of enzymes containing heme as a cofactor that function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown.
P450 enzymes
Protection from toxins include
Barries, metabolic transformation and mobilization of toxins for excretion
Phase I detox ( in liver)
oxidation step converting toxins into substance containing a hydroxyl group (-OH)
Phase II detox (in liver)
conjugation reaction adding compounds (gly, So4, met, etc) to products from phase 1 to make the substace water soluble for excretion?
Creating more easily removable compounds that can be excreted from the system
metabolic transformation, phase 1 and phase 2 detox
Reduce ability of toxins to penetrate into system
barriers
exretion occurs in GI tract, kidney, skin and lungs
mobilization of toxins from excretion
Most endogenous/exogenouse toxins cleared through
liver phase 1/2
acetaminophen does not need to be cleared through phase but can go direction in phase
phase 1, phase 2
detox mechanisms include
(1) enhanced tolerance (2) induced mobilization (3) increase metabolic conversion rates (4) induce extretion of toxins
exogenous toxins are found high in
brain, bone
endogenous toxins may have systemic effects
increase ROS in most cells
GI microbial toxins
high OA overgrowth from bactreia or fungi
Total toxin exposure
exogenous, microbioal, endogenous
NH3 exceeding urea cycle capacity leads to high
orotate
plasma ammonia levels
an important evaluation of toxicity from NH3 that can occur in liver and kidney
Creatinine can indicate
kidney damage from autoimmune disease or toxicity
excretes bilirubin
glucuronidation
what can lead to elevated NH3
high bacterial markers, exercise,
amonia clearance requires
ATP, MN and MG
high orotate and citrate in urine =
low arg
things that depress liver function
infections by virus, bacteria or parasites, drugs, toxins, excess alcohol
3 classes of biotransformation enzymes
oxygen radical conversion, ammonia removal, immunocompetence
toxins must pass through the _____ memembrane to enter the cell for phase I and II detox to occur
hepatocytes plasma
toxins enter hepatocyte plasma via
(1) passive diffusion (2) active transporters such as OAT, OATP and NTCP
when the hepatocyte is funcioning optimally, toxin intake rates
parralel hepatic clearance rates
liver phase 1 (3 steps)
oxidation, reduction (less commmon and important) and hydroxylation and hydroplysis
hydroxylation occurs via
cytochrome P450 monooxygenases
hydroxylation detoxes many
drugs and steroids
CYP enzymes
most importnat detox enzymes
detox of carcinogens and toxins
CYP1A1
activation of carcinogenic amines and aflatoxin B
CYP1A2
involved in biotransformation of many drugs
CYP1A4
Involved in oxidation of volatile environmental chemicals and anesthetics
CYP2E1
Monooxygenase
what makes every compound more water soluble
What is always at the core of Cytochrome P450
iron