MCP Flashcards
clinical correlation: rare, inherited, mutations that encode sterolin transporters, increased phytosterols in blood and tissues, tuberous xanthomas, coronary atherosclerosis
sitosterolemia
clinical correlation: low bile salts or high cholesterol, treat with laproscopic cholesystectomy
cholelithiasis
bile (acids/salts) are better detergents because they are more amphipathic
conjugated ionized bile salts are better detergents
bile salts lost in feces daily is (more than/less than/equal to) the bile salts made daily by liver
equal to
how do statins lower cholesterol
they are structural analogs of HMG and competitively inhibit HMG CoA R-ase, inhibiting cholesterol synthesis
RDS in cholesterol synthesis (substrate, product, enzyme)
HMG CoA to mevalonate by HMG CoA Reductase
8 steps from mevalonate to cholesterol. Number the carbons in each intermediate
mevalonate has 6C > 5PPmevalonate has 6C > IPP has 5C >DMPP has 5C > GPP has 10C > FPP has 15C > squalene has 30C > lanosterol has 30C > cholesterol has 27C
in the synthesis of cholesterol, what is the purpose of release of pyrophosphate
makes reactions irreversible
in the synthesis of cholesterol, what is the purpose of phosphorylation
makes intermediates more soluble in water
which intermediates in synthesis of cholesterol need carrier proteins
squalene, lanosterol, cholesterol
(insulin/glucagon) upregulates HMG CoA R-ase activity
insulin (HMG CoA R-ase=synthesis of cholesterol=anabolic)
(phosphorylation/dephosphorylation) INACTIVATES HMG CoA R-ase
phosphorylation
high cholesterol (increases/decreases) HMG CoA R-ase activity
decreases (binds sterol sensing domain on the enzyme which triggers ubiquitination>proteasomal degradation, also binds sterol sensing domain on SCAP so SCAP-SREBP2 can’t migrate to golgi to cleave SREBP to increase txn)
Apo _: Structural protein (HDL); LCAT activator; Involved in RCT; ligand for ABCA1 and SR-B1
A-I
Apo _: structural protein HDL, inhibits LCAT,
A-II
Apo _: structural protein (VLDL, LDL), VLDL assembly, LDLR binding, one copy for each VLDL
B-100
Apo _: structural protein (LDL, VLDL), VLDL assembly, LDLR binding, produced in intestine, chylomicron metab
B-48
Apo _: can be exchanged freely among lipoprotein particles, important for TG metab bc they interfere with recognition of ApoE by LP receptors or displace ApoE from lipoproteins
C’s
Apo C (I/II/III): LCAT activator
I
Apo C (I/II/III): lipoprotein lipase activator
II
Apo C (I/II/III): inhibits lipoprotein lipase
III
Apo E (2/3/4): normal
3 edited
Apo E (2/3/4): risk for type III hyperlipidemia
3
Apo E (2/3/4): Alzheimer’s
4
Apo _: modulates thrombosis/thrombolysis
(a)
(DRI/RDA): defined as the amount sufficient to meet the nutrient requirement of 97-98% of healthy individuals in a given group
RDA = recommended daily allowance, varies for different populations
two water soluble vitamins
B and C
deficiencies arise more rapidly with (water/lipid) soluble vitamins
water solulbe, since they are excreted efficiently
Vit _: functions in visual cycle, antioxidant, retinoic acid acts as a hormone
A
Vit _: deficiency causes night blindness, xeropthalmia, follicular hyperkeratosis, anemia (despite normal iron intake), poor growth in children, increased susceptibility to cancer
A
three groups susceptible to Vit A def
poor, malnourished, premature babies
Vit _: functions in maintaining bone, calcium homeostasis, acts as a hormone
D
Vit _ def: rickets, osteomalacia, increased susceptibility to breast and other cancers, diabetes, and infection
D (toxic levels of Vit D can lead to high levels of calcium and bone loss–rare)
three groups susceptible to Vit D def
poor, elderly, alcoholics
Vit _: functions in localization of enzymes required for blood clotting, helps catalyze add’n of gamma-carboxyglutamate to clotting enzymes
K
Vit _ def: results in easy bruising, bleeding, hemorrhage
K
four groups susceptible to Vit K def
NEWBORN INFANTS, patients on long term antibiotics, elderly, pts with defects in fat absorption
why are newborns so susceptible to Vit K def
lack intestinal bacteria that makes vitamin K, and deficiency can lead to brain bleed. Vitamin K shot now given at delivery (prophylactic measure)
why are people on long term antibiotics susceptible to Vit K def
antibiotics kill intestinal bacteria that make vit K
Vit _: functions as antioxidant, protects membranes from damage, prevents oxidation of LDL
E
Vit _ def: CVD, neurological symptoms
E
Vit _: cofactor for oxidases
involved in collagen
formation, required for synthesis of steroids in stress
response (response to
trauma), aids absorption of iron, has antioxidant
activity
C
Vit _ def: mild causes bruising and immunocompromise, severe causes scurvy
C
name disease: decreased wound healing, osteoporosis, hemorrhage, anemia, fatigue
scurvy
two groups susceptible to Vit C def
smokers, ppl w/ poor diet
severe stress or trauma rapidly reduces serum Vit _
C
In addition to smoking, long-term treatment with aspirin,
oral contraceptives, and corticosteroids can decrease
serum vitamin _
C
corkscrew hairs and pinpoint hemorrhages are characteristic of ____ (dz)
scurvy, also severe periodontal dz
name B1
thiamine
name B2
riboflavin
name B3
niacin
name B5
pantothenic acid
name B6
pyridoxine
name B9
folate
name B12
cobalamin
name the hematopoietic B vitamins (two)
B9 and B12
name the energy releasing B vitamins (six)
B1, B2, B3, biotin, B5, B6
symptoms of def in energy releasing B vitamins show up first where
in rapidly dividing tissues–Nervous system also affected because of high
energy demand:
Peripheral neuropathy—tingling of extremities
Depression, confusion
Lack of coordination
Malaise
Vit _: required cofactor for several enzymes in energy metabolism, critical in nervous system
B1 (TPP)
name disease: • Moderate/severe thiamine deficiency, most commonly seen in chronic alcoholics • Characterized by mental disturbance, unsteady gate, and uncoordinated eye movements • Occasionally congestive heart failure
Wernicke-Korsakoff syndrome
name disease: Very Severe thiamine deficiency: 19th century
Japan- switch to polished rice induced disease
Beri Beri
Vit _: Precursor of FAD and FMN, key coenzymes for redox reactions involved in energy metabolism
B2
Vit _ def: —rash around nose, inflammation of mouth and tongue, burning and itchy eyes, light sensitivity
ariboflavinosis B2
Vit _: Precursor of NAD and NADP coenzymes important in redox reactions of energy metabolism • Given to patients with hyper-cholesterolemia or hypertriglyceridemia (high doses)
B3
Vit _ def: pellagra
B3 niacin
name disease: dermatitis,diarrhea,
and mental symptoms
(confusion, memory
loss, mania)
Pellagra
group susceptible to B3 def
People with corn or
millet based diets
Vit _: coenzyme for several carboxylases. Def is rare but can be caused by eating a lot of raw eggs
biotin
Vit _: Required for the synthesis of CoA CoA is a coenzyme for up to 70 different enzymes Required for TCA cycle and metabolism of all fats and proteins
B5
Vit _: Required for glycogen
breakdown,and
synthesis of GABA
and heme
B6. Also precursor of pyridoxal phosphate PLP enzyme cofactor
group susceptible to B6 def
patients treated with TB drugs
Vit _ def: Mild—irritability, nervousness, depression Severe—peripheral neuropathy, convulsions, decreased glucose tolerance, hyperhomocysteinemia (cardiovascular risk), anemia
B6
Vit _: functions as precursor of THF, co enzyme involved in generating precursors for DNA and protein synthesis
B9 folate
Vit _ def: neural tube defects in newborns of deficient mothers
–macrocytic anemia, hyperhomocysteinemia (cardiovascular risk)
B9 folate
five groups susceptible to folate B9 def
pregnant women, elderly, alcoholics, patients with long-term drug treatments, genetic polymorphisms in folate metab
folate supplementation during pregnancy can prevent
neural tube defects
Vit _: functions as coenzyme in methionine synthesis and in conversion of methylmalonyl CoA to succinyl Coa, needed in folate metab
B12 cobalamin
Vit _ def: pernicious megaloblastic anemia with demyelination
B12 cobalamin (need intrinsic factor)
three groups susceptible to B12 cobalamin def
elderly, patients with malabsorption dz, long-term vegetarians
mineral _: functions as a major component of bone, signaling, coagulation, muscle contraction, neurotransmission
calcium
mineral _ def: muscle cramps, osteoporosis. severe: rickets
calcium
three groups susceptible to calcium def
children, adult women, elderly
mineral _: essential for enzymes using ATP as substrate, present at high levels in bone
magnesium
mineral _ def: weakness, tremors, cardiac arrhythmia
magnesium
two groups susceptible to magnesium def
alcoholics, patients taking diuretics/severe vomiting and diarrhea
mineral _: major component of bone, constituent of nucleic acids and membrane lipids, required in all energy producing reactions
phosphorus
mineral _ def: rare, can result in rickets, muscle breakdown, weakness, seizure
phosphorus–abundant in food supply
mineral _: functions in O2/CO2 transport, oxidative phosphorylation, cofactor in cytochromes, redox
iron
mineral _ def: microcytic hypochromic anemia, decreased immunity
iron
four groups susceptible to iron def
children, menstruating women, pregnant women, elderly
Reduction of Fe3+ to Fe2+ is promoted by vitamin _ in
diet. (Vitamin _ deficiency causes mild anemia.)
C
Low pH in stomach helps release Fe_+ from ligands and makes it bioavailable.
3+
iron is (free/escorted) in circulation and cells
escorted bc of potential for redox damage
___ (mineral) deficient anemia: microcytic, small, pale RBCs, less Hb is produced
iron deficient
name disease: long term iron toxicity
hemochromatosis
name dz: –iron overload leads to iron deposits in multiple
tissues. Leads to compromised liver, pancreatic, and cardiac function.
–ultimately can compromise mitochondrial
function leading to lactic acidosis
hemochromatosis
most common cause of death due to toxicity in
children under 6, comes from consumption of adult supplements
acute iron overdose in children
mineral _: assists iron absorption thru ceruloplasmin, cofactor for enzymes required in collagen synthesis, fatty acid metab, elimination of ROS
copper
mineral _ def: rare. anemia, hypercholesterolemia, fragility of large arteries, bone demineralization and demyelination
copper
two groups susceptible to copper def
Menkes’ genetic syndrome, pts consuming excessive zinc
____ disease comes from mutations in
Cu transporter ATP7A
Menkes
Need to transport \_\_ into Golgi to supply \_\_ To enzymes like Lysyl oxidase. These enzymes are secreted without \_\_ if ATP7A is missing
copper
____disease comes from mutations in ATP7B, a
relative of ATP7A, but results in copper overload.
Wilson’s
____ disease: Copper is not sequestered properly, and accumulates in
liver with severe liver and nervous system symptoms.
Results in liver failure and liver cancer.
Wilson’s
mineral _: cofactor for over 300 metalloenzymes, plays a structural role in many proteins
Zn
mineral _ def: Poor wound healing, dermatitis, reduced taste acuity, poor growth and impaired sexual development in children
Zinc
four groups susceptible to Zn def
alcoholics, elderly, people with malabsorption or kidney disease
earliest symptom of Zn def
dermatitis
mineral _: component of chromodulin which facilitates insulin binding to its receptor
chromium
mineral _ def: impaired glucose tolerance from reduced insulin effectiveness
chromium
one population susceptible to chromium def
those with impaired glucose tolerance
mineral _def: goiter, hyper/hypo thyroidism
iodine
mineral _: incorporated into T3 and T4, regulates BMR
iodine
Low [I] stimulates increased thyroid stimulating
hormone, results in enlarged thyroid characteristic
of ____
goiter
mineral _: component of antioxidant enzymes (glutathione peroxidase), component of deiodinase enzymes involved in T3/T4 metab
selenium
mineral _ def: Keshan disease (in areas with little \_\_in soil)— cardiomyopathy and cretinism
selenium
mineral _ is a cofactor in arginase, pyruvate carboxylase,
superoxide dismutase
manganese
mineral _ is a cofactor in xanthene oxidase
molybdenum
mineral _ is incorporated into bones and teeth, strengthening them
fluoride
boron is involved in ___formation
bone
mineral _ is a component of amino acids and used in certain post-translational modifications
sulfur
children are most susceptible to what two mineral deficiencies
iron and calcium
teenagers are most susceptible to what kind of vitamin and mineral def
calcium, magnesium, Vitamin A, C, B6
women are most susceptible to what five vitamin and mineral def
iron, calcium, magnesium, B6, folate
elderly are most susceptible to what five vitamin and mineral def
B6, B12, D, Zn, chromium
alcoholics are most susceptible to what three vitamin/mineral deficiencies especially
folate, B6, thiamine. but multiple deficiencies
which apoprotein is only made in the intestine
B48
density of chylomicron is (proportional/inversely proportional) to size
inversely proportional to size. more proteins:lipids = more dense
nascent (VLDL/chylomicron): B100 on surface
VLDL
nascent (VLDL/chylomicron): B48 on surface
chylomicron
HDL supplies __ and __ apoproteins to chylomicrons and VLDL
C II and Apo E
When VLDL loses its CII and Apo E to HDL, it becomes ___ and is endocytosed by liver
LDL
before entering the capillaries, VLDL and chylomicrons have (more/less) TAG and (less/more) cholesterol esters
more TAG, less cholesterol esters. After the capillary, more cholesterol esters than TAG.
function of ___: provide cholesterol to peripheral tissues and return it to liver
LDL
CURL=
compartment for uncoupling receptor and ligand (LDL receptor and LDL in clathrin coated pit)
the LDL binding region on LDL receptor is rich in ____ (aa) residues
cysteine
which domain of the LDL receptor associates with clathrin pit and initiates endocytosis
6, the cytosolic domain
which domain of the LDL receptor is the alpha helix through the bilayer
5
which domain of the LDL receptor makes the binding domain more accessible to LDL by moving it away from the membrane
3 and 4
which domain of the LDL receptor undergoes a conformational change in low pH, causing release of LDL from the receptor
2
__: formed by addition of lipids to Apo A I
HDL
__: serves as a circulating supplier of Apo C II and Apo E
HDL
shape of nascent HDL
discoid–contains phospholipids and Apo A, C, E. Takes up cholesterol from peripheral tissues and returns it to liver
enzyme in reverse cholesterol transport
LCAT
when macrophages consume excess oxidized lipoproteins, they become:
foam cells
foam cells release ____ and ____ which cause the migration of myofibroblasts to the intima where they proliferate and take up lipid
growth factors and cytokines
not produced in ob/ob mice (leptin/leptin receptors)
leptin–from fat tissue
not produced in db/db mice (leptin/leptin receptors)
leptin receptors–hyth
lysyl oxidase is involved in the cross-linking step in Type _ collagen
I
appetite hormone released by empty stomach (leptin/ghrelin/CCK)
ghrelin
(visceral/peripheral) obesity is characteristic of metabolic syndrome
visceral (android)
where is the leptin receptor synthesized
hyth
niacin (has/does not have) significant stores in tissues
has
prolyl and lysyl hydroxylase utilize vitamin _ as a cofactor
C (ascorbate)
which of the following are required for collagen biosynthesis: (lysyl/prolyl/hydroxylase)
all three
leptin release normally (increases/decreases) with body mass
increases
UCP1 promotes adaptive thermogenesis in the presence of _____ (substrate for symporter)
free fatty acids
Appetite-inhibiting signal released from endocrine cells associated with the colon and distal small intestine that acts on cells in the hypothalamus: (CCK/PYY3-36)
PYY3-36
required for collagen biosynthesis: (Vit C/copper/iron/biotin)
Vit C, copper, iron
Vit B_ is required for biosynthesis of B_ from tryptophan
Vit B2 required for synthesis of B3
Vit B_ is required for transformation of inactive B6 to active B6
B2
formation of CoA requires _____ acid, a B-complex vitamin
pantothenic
in metabolic syndrome, which are elevated: (insulin in blood/triglyceride in blood/HDL in blood/blood pressure)
insulin, triglyceride, blood pressure. HDL is low
name the B vitamin that: reverses pellagra, co-factor of redox, no significant stores in tissues, used in conjunction with statins for tx of hypercholesterolemia
niacin B3
def in which can correlate to anemia: (B12/B2/folic acid/iron/copper)
all except B2 (so: folic acid, B12, iron, copper)
lysyl (oxidase/hydroxylase) contributes to cross linking in Type I collagen
oxidase
MOI G6PD deficiency
X linked
is electrophoretic mobility of G6PD related to activity of enzyme
no
what is the evolutionary benefit of G6PD def
protects against malaria
what are Heinz bodies in G6PD def
insoluble precipitates that become attached to cell cytoskeleton > RBC gets destroyed in spleen
(superoxide/NADP+) is produced in the phagosome as a result of NADPH oxidase
superoxide
(superoxide/NADP+) is produced in the cytosolas a result of NADPH oxidase
NADP+
why do normal phagocytes reduce the dye NBT only after they have been activated
superoxide reduces NBT
what molecular moiety donates an electron directly to O2 in the respiratory burst oxidase reaction
cyt b558
in what cells is myeloperoxidase found
neutrophils
what rxn is catalyzed by myeloperoxidase
H2O2 to HOCl
what is the effect of opening the Permeability Transition pore on the IMM
dissipates membrane potential > can’t make ATP > necrotic cell death
how do chelators that bind iron or copper tightly prevent reperfusion injury
prevent the Fenton reaction, can’t make OH radical
allopurinol inhibits xanthine oxidase, which inhibits formation of which free radical
superoxide
hydroxyl radicals (are/aren’t) effectively scavenged by SOD and catalase
aren’t
enzyme that converts hydrogen peroxide to hypochlorous acid in the phagosome.
myeloperoxidase
Produced in the oxidation of hemoglobin by molecular oxygen: (superoxide/H2O2/OH radical/HOCl)
superoxide
substrate for catalase: (superoxide/H2O2/OH radical/HOCl)
H2O2
produced by myeloperoxidase (superoxide/H2O2/OH radical/HOCl)
HOCl
(superoxide/H2O2/OH radical/HOCl): generated in the nonenzymatic reduction of H2O2 by Fe2+
hydroxyl radical
(superoxide/H2O2/OH radical/HOCl): generated by the decomposition of peroxynitrite (ONOO + H+ –> ONOOH –> OH + NO2
hydroxyl radical
which are least dense (chylomicrons/VLDL)
Chylomicron
During biosynthesis of VLDL in the liver, a large fraction of the total cholesterol in the particle is in the free form because: (ACAT levels are low/lysosomal cholesterol esterase activity is elevated)
ACAT levels are low
When cholesterol levels in the cell are (low/high), S1P protease will be inactive and cleavage of SREBP will not proceed
high
When cells previously growing in a cholesterol-free environment are exposed to excess LDL cholesterol, SCAP will (remain in/exit) the ER
remain in
Which lipoprotein has the following approximate composition (by weight), 50% cholesterol/cholesterol esters : 10% triacylglyerols : 20% protein? (HDL/LDL)
LDL
reverse cholesterol transport would be reduced under (high LDL levels/Apo AI deficiency)
Apo AI def
Apo __ is a risk factor for atherosclerosis because it accumulates to higher levels in VLDL than other alleles do
E2
(VLDL/LDL) has a half life in serum of 3 days
LDL
Both pancreatic and lipoprotein lipases (require CII for efficient binding of enzyme to substrate/hydrolyze ester bonds)
hydrolyze ester bonds
Compared to newly assembled chylomicrons, chylomicron remnants have a (lower/higher) ratio of TAGs to cholesteryl esters
lower
Compared to newly assembled chylomicrons, chylomicron remnants have a (lower/higher) density
higher
(Long-chain fatty acids/TAGs) used by the heart as fuel may be:
long chain fatty acids
When cholesterol levels in the cell are (low/high), S1P protease will be inactive and cleavage of SREBP will not proceed
high
obesity is a (minor/major) risk factor for atherosclerosis
minor
synthesis of cholesterol requires _ HMG-CoA’s
6
A decrease of cholesterol-7a-hydroxylase (CYP7A1) activity would (increase/decrease) bile acid production
decrease
A decrease in cholesterol-7-hydroxylase (CYP7A1) activity would (increase/decrease) risk for atherosclerosis
increase
(VLDL/LDL/HDL): approx 50% protein by weight
HDL
(hepatic/lipoprotein) lipase hydrolyzes triglycerides in VLDL remnants
heptaic lipase
(LCAT/lipoprotein lipase) involves hydrolysis of TG
lipoprotein lipase
Apo _ is the ligand for LDL uptake through the LDL receptor
Apo B-100
HMG-CoA reductase: (phosphorylated/unphosphorylated) enzyme is more active
unphos
Type III hyperlipoproteinemia is: associated with presence of Apo _
E2
Type III hyperlipoproteinemia is associated with (reduced/elevated) TG
elevated
Type III hyperlipoproteinemia is associated with abnormal migration of (LDL/HDL)
LDL
Type (III/II) hyperlipoproteinemia is associated with a mutation in the LDL receptor
II
heavy drinking: insulin levels go (up/down)
down
As large amounts of ethanol are metabolized, serum (glucose/lactate) concentration goes down
glucose
alcohol dehydrogenase is found in the (ER/cytoplasm/mit) of liver cells
cytoplasm
Result of acat def (increase/decrease) in amount of cellular cholesterol esters
Decrease
