Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
264 Cards in this Set
- Front
- Back
|
which foods are Krebs intermediates?
|
ALL of them
|
|
|
Krebs = final stage for
|
ALL foods that are oxidized to CO2 and H2O
|
|
|
4 cofactors that BOTH pyruvate DH and aKGDH require:
|
1. thiamine pyrophosphate
2. CoA 3, FAD 4. NAD |
|
|
the cofactors that pyruvate DH and aKGDH require are derived from:
|
1. thiamine
2. pantothetic acid 3. riboflavin 4. niacin |
|
|
regulation of Krebs: NADH inhibits:
|
MANY points
|
|
|
in Krebs, what does ATP inhibit?
|
**aKGDH**
|
|
|
when energy needs are satisfied, Krebs is:
|
**shut down**,
and intermediates are shunted to other pathways |
|
|
**Krebs substrates are products, so they inhibit:**
|
**their own steps**
e.g. citrate will inhibit citrate synthase |
|
|
***Krebs does not experience any:
|
*hormonal* regulation
|
|
|
***what does electrical stimulation do to Krebs?***
|
***overrides inhibition*** from NADH, ATP
=> activation of Krebs |
|
|
which enzyme is required in order for AA's to get into Krebs?
|
**transaminase**
|
|
|
***transaminase requires ____________ as cofactor***
|
pyroxidol P,
from B6 |
|
|
interconversion in Krebs: carbs can become:
|
fat and nonessential AA's
|
|
|
interconversion in Krebs: protein =>
|
carbs (from nonessential) and fat (from all AA's)
|
|
|
interconversion in Krebs: fat =>
|
NEITHER carbs NOR protein
- both C's of fat are lost before succinate |
|
|
***Krebs requires constant supply of OAA to: ***
|
combine with ACoA***
- but OAA is continually depleted by GNG |
|
|
carbs => BOTH
|
OAA and ACoA
(via pyruvate carboxylase and pyruvate kinase, respectively) |
|
|
Protein => BOTH
|
OAA and ACoA
|
|
|
Fat => ONLY
|
**ACoA**
=> only fate of fat is to be oxidized in Krebs |
|
|
***glycogen synthesis/breakdown is regulated by:***
|
hormones
|
|
|
glycogen =
|
alpha 1,4 linkages
with a1,6 branch points |
|
|
what's the purpose of glycogen branch points?
|
to have multiple ends and thus cleave off many glucose mlcls at once
|
|
|
which 2 enzymes are necessary for glycogen synthesis?
|
1. ***glycogen synthase***
2. branching enzyme |
|
|
***glycogen synthase ONLY makes:***
|
a1,4 linkages
(branching enzyme makes the a1,6 after it) |
|
|
which 2 enzymes are necessary for glycogen breakdown?
|
1. ***glycogen phsphorylase***
2. debranching enzyme |
|
|
***glycogen phsophorylase ONLY cleaves:***
|
a1,4 links
|
|
|
the debranching enzyme converts:
|
a1,6 links to a1,4
so that glycogen phosphorylase can cleave |
|
|
***UDP-glucose = example of:
|
high-energy, activated sugar
- glycogen synthase uses this high energy to drive addition of glucose to glycogen chain |
|
|
glucose-6-phosphatase is only found in the
|
liver and kidney
|
|
|
effect of hormones on glycogen: Glucagon/EPI => cAMP =>
|
PKA => P'n of glycogen phosphorylase kinase (GPK) => P'n of glycogen phosphorylase => activation => glycogen breakdown
meanwhile, PKA => P'n of glycogen synthase => *inhibition* of glycogen synthase |
|
|
|
|
|
|
EPI has two kinds of receptors:
|
alpha and Beta adrenergic
|
|
|
EPI's alpha receptor =>
while Beta => |
Ca2+ release;
cAMP |
|
|
subunits of GPK: out of the 4, 2 are activated by:
|
PKA
=> *some* activation of GPK => *some* activation of glycogen phosphorylase |
|
|
GPK is somewhat active when PKA activates 2 of its subunits, but it's MOST active when:
|
BOTH PKA **and** calmodulin are activating its subunits
|
|
|
***muscle doesn't have alpha adrenergic receptors*** but the same maximum level of glycogen breakdown is achieved by:
|
electrical stimulation => Ca2+
along with EPI, => max glycogen breakdown **in exercising muscle** |
|
|
PPS is driven **entirely** by:
|
mass action
|
|
|
products of PPS:
|
NADPH, ribose-5-P, or both
|
|
|
NADPH production is regulated by:
|
the cell's need for NADPH
- NADPH will inhibit G6PDH if the cell has enough |
|
|
what is ribose-5-P used for?
|
RNA, DNA synthesis
|
|
|
the NonOx portion of PPS is
|
***reversible***
|
|
|
NonOx PPS = "carbon shuffling" between:
|
ribULOSE-5-P
and glycolysis intermediates (F6P, G3P) |
|
|
**2 enzymes necessary for NonOx PPS:**
|
1. transketolase
2. transaldolase |
|
|
BOTH transketolase and transaldolase require the cofactor:
|
***thiamine pyro-P***
|
|
|
what determines whether a cell uses Ox or NonOx PPS?
|
**its needs at the time**
|
|
|
to get both NADPH AND ribose-5-P, use
|
the Oxidative Portion of PPS
|
|
|
to get ONLY ribose-5-P, use
|
the NonOx portion of PPS
- can start with F6P, G3P and work backward |
|
|
to create ONLY NADPH, use
|
BOTH Ox and NonOx
- Ox => NADPH - NonOx = > glycolysis intermediates |
|
|
G6PDH deficiency ~
|
massive hemolysis
(b/c G6P can't work in PPS => membranes not protected from ROS) |
|
|
2 types of membrane damage:
|
1. prot. disulfide formation
2. mixed disulfide formation |
|
|
***GSH =
|
***reduced glutathione***
|
|
|
what does reduced glutathione (GSH) do?
|
1. protects cell damage from ROS
2. prevents oxidation of proteins |
|
|
what 2 things are required to keep glutathione in reduced state?
|
1. glutathione reductase
2. NADPH |
|
|
***reduction of prot. and mixed disulfide formation is done by 2 proteins:***
|
1. thioredoxin
2. glutaredoxin |
|
|
cells with mit. can make
|
NADPH in other pathways
|
|
|
b/c RBC's don't have mit, they are dependent on _______________ for NADPH
|
***G6PDH***
|
|
|
some drugs produce large amounts of free radicals/mixed disulfides; what should you check for before administering such drugs?
|
G6PDH levels
|
|
|
what kind of AA's CANNOT be used to synthesize glucose?
|
**ketogenic** AA
|
|
|
ALL AA's can be
|
catabolized for energy
|
|
|
there is preferential shunting of glucogenic AA's to make glucose via the
|
Ala-Glucose cycle
(GNG) |
|
|
protein quality =
|
how well the item provides ALL 20 AA's
|
|
|
Arginine is special; it's
|
conditionally essential - extra is needed during growth, illness, etc.
|
|
|
Arginine helps make:
(3) |
1. urea
2. creatine 3. NO |
|
|
NO. metabolism depends on:
|
the concentration of Arginine in the body
|
|
|
Creatine P "immediately" transfers
|
P to ATP
|
|
|
CP =
|
energy *storage* in muscle
|
|
|
both creatine and CP become
|
creatinin
=> urine |
|
|
ATP + CP ~
|
+5 seconds of max exertion
|
|
|
normally, ATP production is 2.5x slower
|
w/o CP
|
|
|
Creatine Kinase isozymes are dimers of 2 subunits:
|
M and B
|
|
|
CKmm ~
|
skeletal muscle
|
|
|
CKmB ~
|
***cardiac*** muscle
(CK = creatine kinase) |
|
|
***increased serum concentrations of CKmB ~
|
myo infaction
|
|
|
NO = NT in
|
many systems
|
|
|
NO is a gas, so it diffuses through the membrane
|
easily
|
|
|
***NO acts by increasing levels of:***
|
**cGMP**
|
|
|
NO is a potent vasodilator - it relaxes
|
SM
|
|
|
NO also causes
|
erection
|
|
|
what is NO used to treat?
|
angina pectoris
(insufficient flow of blood to the heart) |
|
|
glutamate =
|
excitatory NT
|
|
|
GABA =
|
ihibitory NT,
a derivative of glutamate |
|
|
which AA are DO, NOR, and EPI made from?
|
tyrosine
|
|
|
which AA is SER made from?
|
Tryptophan
|
|
|
which AA is Histamine made from?
|
histidine
|
|
|
Parkinson's disease lacks
|
DO in the brain
- need to administer L-dopa, which can cross BBB - then it's converted to DOpamine |
|
|
what does MAO do?
|
***inhibits*** DO, NOR, and SER
|
|
|
how does MAO inhibit NT's?
|
by removing NH2 from them
(=> urea) |
|
|
errors in AA, N metabolism =>
|
mental retardation if untreated
|
|
|
2 diseases of AA metabolism error:
|
1. PKU
2. Maple Syrup disease |
|
|
Maple Syrup disease =
|
defect in BCAA catabolism
|
|
|
PKU =
|
**Phe-hydroxylase deficiency**
|
|
|
in PKU, Phe builds up because:
|
it's not being converted to tyrosine
|
|
|
Phe is converted to
|
phenylpyruvate
|
|
|
accumulation of Phe =>
(2) |
1. mental retardation
2. mousy urine |
|
|
treatment of PKU =
|
lifelong limit of Phe in diet
- avoiding aspartame |
|
|
aspartame contains
|
high levels of Phe
|
|
|
hepatic encephalopathy =
|
decrease in brain function due to failure of liver to remove ammonia
= hyperammonia |
|
|
***NH3 enters the brain's blood supply
|
easily
|
|
|
NH3 in brain's blood supply is converted to
|
glutamine
=> accumulation => coma, death |
|
|
2 other problems with excess NH3 in brain:
|
1. excess glutamine becomes glutamate => excitatory seizures
2. uses up aKG => energy metabolism defects |
|
|
the unionized/nonpolar form of a drug is often
|
the form of the drug that's reabsorbed
|
|
|
oral administration does fall under
|
the first pass effect
|
|
|
phase I transformation facts:
(2) |
1. addition of functional group
2. small increase in hydrophilicity |
|
|
phase I transformation rxns include:
(2) |
1. RedOx
2. Hydrolysis |
|
|
Oxidation =
(3) |
1. lose electrons
2. lose H 3. gain O |
|
|
Reduction =
|
1. gain electrons
2. gain H 3. lose O |
|
|
which kind of enzymes are responsible for the majority of metabolic rxns?
|
***CYtochrome P450's***
|
|
|
CYP 450's are
|
**oxidases**
|
|
|
CYP450's are membrane-bound enzymes with
|
large active sites
- use heme/Fe |
|
|
***each CYP450 can bind to
|
***MANY different drugs***
|
|
|
what do CYP450's oxidize?
|
otherwise-inert mlcls
|
|
|
what do CYP450's do, chemically?
(2) |
1. pluck H off
2. shove OH on |
|
|
prodrug =
|
precursor that can be either activated or inactivated
|
|
|
dehydrogenases are:
|
**oxidases**
|
|
|
where do Phase I and II occur?
|
**in the liver**
|
|
|
hydrolysis =
|
add H2O to break mlcl up
|
|
|
DRESS =
|
severe immune response b/c you're missing hydrolases
|
|
|
both Phase I and II are used for:
|
synthesis
e.g. both necessary for steroid synthesis |
|
|
general mechanism of Phase II:
|
*transferase* takes a piece of cofactor,
adds it to the drug |
|
|
Phase II rxns are used for BOTH
|
metabolism AND synthesis
e.g. of synthesis = NOR to EPI |
|
|
***phase II can come before phase I, and
|
Phase I can is NOT a requirement for phase II
|
|
|
main mechanism of Phase II =
|
**conjugation**
|
|
|
conjugation =
|
the addition of a **hydrophilic** functional group, to aid in excretion
- large increase in hydrophilicty |
|
|
acetaminophen toxicity: acetaminophen is normally converted to an intermediate, then
|
conjugated to glutathione
|
|
|
too much acetaminophen =>
|
some of the intermediate converted to hepatotoxic protein
|
|
|
2 mechanisms of variability in drug metabolism:
|
1. genetic polymorphisms
2. epigenetic, individual differences |
|
|
genetic polymorphisms =
|
mutations that change drug amount or activity
|
|
|
e.g. of genetic polymorphism: TPMT takes 6MP and makes it inactive;
|
allelic variants of TPMT produce all sorts of different activities, including ones that lead to toxicity
|
|
|
**6MP dosing should take into account:
|
TPMT genotype
|
|
|
e.g. of genetic variability: CYP2D6
|
amount in a person is allelically variable
|
|
|
CYP2D6 is responsible for metabolizing:
|
25% of all clinical drugs
|
|
|
you can treat most people with the same dose of drug, but for those who either less or more CYP2D6, you need to
|
lower dosage,
and increase dosage, respectively |
|
|
warfarin =
|
anticoagulant
|
|
|
variability in amount of CYP-C9 =>
|
functional overdose of warfarin
- **diminished capacity of CYP-C9 to metabolize warfarin** => normal dose = overdose |
|
|
epigenetics ~
|
age, disease, diet
|
|
|
Induction =
|
increase in expression of specific enzymes in response to dosage of drug
- takes days |
|
|
GPCR's are the largest
|
family of cell surface receptors
|
|
|
GPCR's mediate response to an incredible diversity of signaling mlcls:
|
hormones, NT's, light, etc
|
|
|
GPCR structure =
(3) |
1. 7 membrane-spanning segments
2. ec segment 3. ic segment |
|
|
extracellular segment of GPCR's:
(3) |
1. N-terminus
2. 3 ec loops 3. potential for N-linked glycosylations |
|
|
intracellular segment of GPCR's
(2) |
1. C-terminus
2. 3 ic loops |
|
|
***transmembrane parts of GPCR's form:***
|
a bundle, in which biogenic amines bind
- peptide hormones bind to ec loops |
|
|
rhodopsin =
|
GPCR
|
|
|
in the inactive state, the salt bridge connects some of the helices; binding of ligand =>
|
breaking the salt bridge => movement of TM helices => exposure of receptor to GEF activity => increased Kd-GDP => GDP kicked off => alpha subunit activated with GTP => effector enzyme
|
|
|
key point: ligand-receptor complex increases:
|
Kd-GDP of the alpha subunit
|
|
|
***a given G-protein can be activated by MANY:***
|
hormone-receptor complexes
|
|
|
2 categories of G-protiens:
|
1. heterotrimeric
2. small monomeric |
|
|
heterotrimeric G-protein =
|
alpha, B, and y subunits
|
|
|
alpha subunit:
(2) |
1, binds GDP, GTP
2. has inherent GTPase activity |
|
|
Beta and y form a tight complex, never
|
come apart
|
|
|
ligand binding stabilizes:
|
the OPEN conformation of the receptor
|
|
|
once GTP is hydrolyzed, alpha subunit
|
dissociates from the effector enzyme and returns to By
|
|
|
RGS =
|
Regulator of G-prot. Signaling
|
|
|
RGS' have
|
**GAP activity**
|
|
|
RGS =>
|
increased kcat activity => decreased alpha activation
|
|
|
in all G-protein situations, the only subunit to regulate **kinases** =
|
alpha
|
|
|
***LOTS of hormones stimulate:***
|
Gs
|
|
|
hormones that stimulate Gs use this pathway:
|
Gs => Ad. cyclase => turns ATP into cAMP => convert inactive PKA to active form
|
|
|
****the pseudo-substrate site blocks the catalytic cleft,
|
inactivating PKA activity when cAMP isn't around
- binding of cAMP to all 4 binding sites => popping pseudo-substrate site out of the way |
|
|
what do the the dimerization/docking domains of PKA do?
|
1. connect regulatory subunits into a dimer
2. bind to different targets |
|
|
which 2 hormones bind to the Gq family of G-proteins?
|
1. angiotensin
2. EPI (via a1 adrenergic receptors) |
|
|
DAG =
|
lipophilic
- stays in the membrane |
|
|
IP3 operates in the
|
cytoplasm
- **regenerated into PIP2** |
|
|
like ALL kinases, PKC has
|
an ATP-binding domain and a substrate-binding domain
|
|
|
how does activation of PKC occur?
|
DAG and Ca2+ bind to it
|
|
|
PKC is NOT a
|
dimer
|
|
|
which hormone uses the Gi family?
|
EPI
(via a2 adrenergics) |
|
|
Gi's affect BOTH
|
**PKA and PKC**
|
|
|
in Gi, what does the alpha subunit do when activated?
|
inactivates Ad. cyc., thereby **INHIBITING** production of cAMP
|
|
|
in Gi, what activates PLCB to eventually activate PKC?
|
**By** subunit
|
|
|
Insulin does NOT stimulate glucose uptake in:
(2) |
RBC's and brain
|
|
|
a decreased state of ionization will increase
|
drug absorption
|
|
|
***only EPI stimulates BOTH:***
|
PKA and calmodulin in the liver
|
|
|
***EPI is more effective than
|
Glucagon
- in liver, etc. |
|
|
the energy needs of the body are greater in __________ than during the fasting state
|
**exercise**
|
|
|
RBC's do NOT synthesize:
|
***FA's***
|
|
|
***antagonist's or agonist's effect is independent of:***
|
**their affinity for the receptor**
|
|
|
Kd is independent of
|
efficacy
|
|
|
what's the major cytochrome of the liver?
|
CYP3A4
|
|
|
treated with courmarin; phenobarbitol is a coumarin-remover; phenobarbitol induces
|
CYP production
- once phenobarbitol is cleared and CYP's are turned over => HUGE increase in coumarin (b/c it's given at the same dose) |
|
|
7 factors that *induce* CYP's:
|
1. aromatics
2. pollution 3. cigarette smoke 4. barbs 5. steroids 6. herbal remedies 7. alcohol |
|
|
Inhibition: one enzyme that's metabolized the same way inhibits another when
|
co-administered
|
|
|
inhibition =>
|
complete loss of one or more enzyme activities
|
|
|
compare timing of induction vs. inhibition:
|
induction = days
inhibition = **immediate** |
|
|
6 factors that increase inhibition
(all sit in the active site of the other enzyme and don't come out) |
1. grapefruit
2. green tea 3. anti-fungal drugs 4. certain antibodies 5. cigarette smoke 6. SSRI's |
|
|
***drug absorption =
|
***drug's movement into the bloodstream***
|
|
|
2 ways that drugs are eliminated?
|
1. excretion
2. metabolism (Phase I and Phase II) |
|
|
rates of metabolism can affect the drug's:
(3) |
1. safety
2. efficacy 3. treatment uses |
|
|
genetic and epigenetic differences in metabolic rates can lead to large differences in
|
drug and metabolite concentrations
- most applicable for non-redundant or rate-limiting enzymes |
|
|
concomitant drug treatments can cause:
|
induciton OR inhibition
- potential adverse effects |
|
|
isoniazoid =>
|
neuropathy if acetylaition (conjugation) is too slow
|
|
|
pregnant women take
|
LOTS of drugs
- Prescription, OTC, supplements |
|
|
A label =
|
no risk
|
|
|
B label =
|
no evidence of risk
|
|
|
C label =
|
risk cannot be ruled out, but benefits outweigh the risk
|
|
|
D label =
|
risk exists; benefits *may* outweigh risk
|
|
|
X label =
|
don't give to pregnant ladies
|
|
|
FDA categories/labels are incomplete descriptions of risk; for example, some drugs are good for:
|
the third trimester, but not the first
|
|
|
teratogens =
|
drugs that cause malformations in fetus
|
|
|
teratogens operate during a particular time
|
check
|
|
|
the degree of the teratogenic effect depends on:
|
the dose
|
|
|
baseline risk of any drug to be a tetatogen =
|
3%
|
|
|
"teratogen" does NOT =
|
alcohol, cocaine, etc.
|
|
|
pregnancy lowers both:
|
1. peak drug concentration
2. steady-state drug concentration ***mostly due to increase in blood volume*** |
|
|
which size of drugs CROSS the placenta?
|
<500 Da
|
|
|
which size is the placenta impermeable to?
|
>1000 Da's
|
|
|
**warfarin passes in to the placenta freely - replace with
|
coumarin**
|
|
|
****placenta and fetal liver have:****
|
limited capacity to metabolize the drugs
|
|
|
***drugs can enter:***
|
breast milk
|
|
|
****6 kinds of drugs that are present in breast milk in large amounts:****
|
1. tetracycline
2. alcohol 3. opioids 4. barbs 5. lithium 6. radio-iodine (chemo) |
|
|
characteristics of infants:
(4) |
1. more water (inc. Vd)
2. less fat 3.higher gastric pH 4. low bile production |
|
|
high gastric pH of infants =>
|
1. inc. absorption of some drugs b/c they're not degraded
2. dec. absorption of weak acids |
|
|
low bile production of infants =>
|
**dec. absorption of lipophilic drugs**
|
|
|
***in general, infants have _______ absorption***
|
SLOWER
|
|
|
contraindicative =
|
you wouldn't want to administer it
|
|
|
***most significant issue for geriatrics =
|
***decrease in liver blood flow***
|
|
|
other problems with geriatrics:
(2) |
1. diseases that affect liver function
2. renal decline |
|
|
geriatrics: very important to know what they're taking,
|
involve the families
be conservative with disage start low |
|
|
***liver problems =>
(2) |
1. decreased first-pass effect
2. slower elimination of most drugs |
|
|
teratogens have effects during particular periods of fetal development - specifically, during
|
3-7 weeks of pregnancy
|
|
|
G-protein signaling problems occur when:
(3) |
1. their expression is reduced
2. their activation is increased 3. their activation is decreased (can cause constitutive activity even in absence of hormone) |
|
|
which two disease correspond to gain of function?
|
1. Cholera
2. FPP |
|
|
what are cholera?
|
gram negative bacteria
|
|
|
cholera bacteria colonize
|
the intestine and produce a toxin that stays there
|
|
|
effect of cholera =
(3) |
1. severe diarrhea
2. water loss 3. electrolyte imbalance |
|
|
cholera toxin = protein with:
(2) |
1. five B subunits (~ host cell recognition)
2. one A subunit |
|
|
what does the A subunit of cholera toxin do?
|
***adds AD-ribose to
G-alpha-s*** |
|
|
adding AD-r to GaS =>
|
***inhibiting GTPase activity***
=> active GaS => inc. cAMP => inc. PKA => ***increased secretion of fluid from interstinal epithilial cells*** |
|
|
what's the overall effect of adding AD-ribose to GaS?
|
***decrease kcat-GTP***
|
|
|
FPP =
|
Familial Precocious Puberty
|
|
|
FPP =>
|
higher basal activity of LH receptor => higher release of testosterone
|
|
|
facets of FPP:
(2) |
1. males only
2. puberty by age 4 |
|
|
flagship characteristic of FPP: testeoterone secretions are:
|
INDEPENDENT of normal regulation by other proteins (LH, GRH)
|
|
|
in FPP, LH and GRH are at normal levels, but testosterone is being released at
|
**higher-than-normal levels**
|
|
|
FPP is cause by mutation to
|
***LH receptor***
Asp -> Gly |
|
|
mutation in LH receptor gene =>
|
****traps receptor in partially-activated conformation****
|
|
|
even mutated receptor is still able to bind regulating hormones, which =>
|
even more activity
|
|
|
what do pertussis bacteria colonize?
|
the cilia of the airways
|
|
|
2 stages of pertussis infection:
|
1. colonization stage => upper respiratory, nonspecific symptoms
2. toxemic stage => prolonged coughing ending in whooping cough |
|
|
pertussis toxin protein structure:
|
5 Beta subunits,
1 alpha subunit |
|
|
the A subunit of the pertussis toxin is responsible for:
|
**catalyzing ADP ribosylation**
|
|
|
what does the A subunit of pertussis toxin add AD-r to?
|
to the Cys residue near C-terminus of ***G-alpha-i***
|
|
|
***effect of Ad-r attached to G-a-i =
|
***TRAPS G-a-i in GDP-bound state => ad. cyc. no longer inhibited => inc. cAMP => PKA => ***Inc. secretion by cilia of lungs*** => coughing
|
|
|
***overall effect of pertussis toxin ADP ribosylation of G-a-i =
|
***DECREASED Kd*** => more-active G-alpha***
|
|
|
AHO =
|
Albright Hereditary Osteodystrophy
|
|
|
clinical features of AHO:
(4) |
1. short stature
2. bone deformities 3. obesity 4. MR |
|
|
AHO is a ____ __ ______ disease
which G-protein subunit is either not expressed enough OR not active enough? |
loss of function;
GaS |
|
|
AHO patients present in one of 2 way:
|
1. PHP 1a
2. PPHP |
|
|
PHP 1a =
|
pseudo-hypo-parathyroidism Type 1a
|
|
|
2 effects of having PHP1a =
|
1. PTH resistance
2. resistance to multiple hormones that normally increase cAMP levels (Glucagon, Gonadotropin, etc.) |
|
|
PPHP =
|
pseudo-pseudo- parahypothyroidism
|
|
|
effect of PPHP:
(1) |
**resistance to PTH**
|
|
|
BOTH
PHP1a and PPHP ~ |
PTH resistance,
but PHP1a also ~ resistance to hormones that normally inc. cAMP |
|
|
2 destinations of PTH:
|
1. bones
2. kidneys |
|
|
effect of PTH on bones:
|
***increases Ca2+ release INTO blood***
|
|
|
effect of PTH on kidneys:
(3) |
1. increased P excretion
2. decreased Ca2+ excretion 3. increased production of Vit. D |
|
|
***resistance to PTH =>***
(3) |
1. hypocalcemia
2. hyperphosphatemia 3. dec. Vit D production |
|
|
***there's only ONE gene for
|
GaS
(two alleles though) |
|
|
loss of one allele (from mother's side or father's) =>
|
50% reduction in GaS activity
|
|
|
***GaS activity can decrease via:
(2) |
1. decreased expression
OR 2. decreased activation |
|
|
not all plasma is
|
filtered
|
|
|
"loading dose" =
|
** Q **
|
|
|
"plasma threshold concentration" =
|
Css
|
|
|
b.i.d. =
|
every 12 hours
|
