Lecture 5 Flashcards
3 main forms of excretion
fecal
urinary
expired air
why is biotransformation necessary
bc most drugs are lipid soluble, weak organic acids or bases and are not readily eliminated - need to be converted to something more water soluble to be eliminated
the outcome of biotransformation is the facilitation of _____
excretion
3 main sites of drug metabolism
liver
kidney
skim
name 4 polar functional groups that can be introduced in phase 1 reactions
OH
SH
NH2
COOH
phase 1 reactions result in _____ molecular weight change
SMALL
phase 2 reactions are __________ reactions
conjugation
with the exception of ____ and ____, phase 2 reactions result in a large increase in hydrophilicity
acetylation and methylation
phase 2 biotransformation can result in both ____ and ____ of xenobiotics
detoxification and activation
phase 1 is ______ and phase 2 is _____
phase 1 is microsomal and phase 2 is cytosolic
2 things involved with GSH conjugation
GST (glutathione transferase) and GSH (glutathione)
enzyme and cofactor involved with sulfation
enzyme = sulfotransferase
cofactor = PAPS
enzyme and cofactor for glucuronidation
enzyme = UDP-GT
cofactor = UDP-GA
acetylation enzyme and cofactor
acetyltransferase
cofactor = acetyl coenzyme A
cofactor and enzyme for methylation
cofactor = SAM
enzyme = methyltransferase
acetaminophen uses what 2 phase 2 pathways
glucuronidation and sulfation
glucuronidation (phase 2) does not reach adult values unitl….
3-6 months of life
antibiotics excreted through the _______ should be used in caution in newborns
liver
most used enzyme in phase 1
CYP450 system
the highest concentration of CYP450 enzymes are found where?
in microsomes of the liver endoplasmic reticulum
(but they are present in all tissues)
what other organelle (besides microsomes) are CYP450 enzymes found
mitochondria
all CYP450 enzymes are _____-containing proteins
heme
the human genome encodes at least ______ P450s and ___ pseduogenes
57 P450s and 29 pseduogenes
SOD
superoxide dismutase
detoxifies superoxide so it doesn’t affect our cells
3 isoforms of superoxide dismutase and where they’re located
CuZnSOD (cytoplasm)
MnSOD (mitochondria)
ECSOD (cytoplasm)
most reactive ROS
hydroxy radical
how is H2O2 toxic
oxidizes lipids in the lipid membrane
3 major organs involved in biotransformation
liver
kidney
skin
what is the name for the “stem cells of the airways”
clara cells
what enzyme converts H2O2 to water
catalase
steps of alcohol metabolism
alcohol to aldehyde by alcohol dehydrogenase
aldehyde to carboxylic acid by aldehyde dehydrogenase
what CYP is also involved in alcohol metabolism
CYP2E1
where is catalase located
peroxisomes
where is ADH (alcohol dehydrogeanse) located
cytosol
where is CYP2E1 located
microsomes
