-
LCAT
- - only in plasma
- -esterifies free dietary cholesterol
-
ACAT 1
- - steroid producing tissues and phagocytes
- - esterifies dietary colesterol
-
ACAT 2
- - liver
- - esterifies dietary cholesterol
-
rate limiters in cholesterol synthesis
- - HMG CoA reductase (inhibited by statins)
- - Mevalonate- rate limiting substrate
-
SREBP
- "sterol regulatory element binding protein"
- -initiates HMG CoA reductase synthesis
- - controlled on gene expression level
- - activated what cholesterol levels are low inside cell
-
apo A-1
- -major protein of HDL
- - activates LCAT
- -HDL and chylomicrons
-
apo B-48
- - chylomicrons only
- - lack LDLr binding domain
-
apo B-100
- - only protein of LDL
- - ligand for LDLr
- - VLDL, IDL and LDL
-
apo C-2
- -activates lipoprotein lipase
- - not on LDL
-
apo C-3
- - lipoprotein lipase inhibitor- not on LDL
-
CETP
- - HDL only
- - cholesterol ester transfer (say to VLDL in LDL syn)
-
apo E
- - binds to B/E receptors on hepatocytes
- - 3 alleles, E3 most common
- - E2/E2 is seen in HLP 3
- - (E4/E4) associated with alzheimers (amyloid deposits)
-
apo (a)
- - extremely atherogenic
- - forms complex with LDL
- - resembles plasminogen and slows blood clot b/d
-
chylomicron synthesis
- - intestinal mucosa
- - acquires apo C-2 and apo E from HDL
-
VLDL synthesis
- - liver
- - trigs are transferred from VLDL to HDL in exchange for cholesterol esters (via CETP) resulting in the formation of LDL
-
Type 1 HLP
- - LPL or apo C-2 defeciency
- - strawberry milkshake blood
- -
increased chylomicrons, huge increased trigs - - turbid retinal vessels,red eruptive xanthomas
- -Tx- low fat, high CHO diet
-
familial hypercholesteremia
- - Type 2a HLP, autosomal dominant
- - LDLr defect
- - reduced LDL clearance=> increased LDL
- -CAD and plaques, xanthalasmas(eye), increased chol synthesis
- - achilles tendon xanthalomas, arcus senilis (grey ring eye)
- - homozygous Tx- liver transplant
- hetero Tx- statin therapy
-
Type 2b HLP
- - increased LDL, delayed VLDL clearance
- - strongly associated with CAD
-
Type 3 HLP
- - apo E2 homozygous
- - xanthomas (increased trigs via increased chylomicrons)
- - CAD/ plaques
-
Type 4 HLP
- - elevated VLDL production
- - associated with metabolic syndrome(insulin resistance), EtOH consumption
-
Wolmans disease
- - defect in lysosomal cholesterol esther hydrolase
- - reduced LDL clearance
-
fibrates
increase lipoprotein lipase activity
-
resins
bind bile acids in the intestine
-
niacin
inhibits FA release from adipose tissue
-
statins
HMG CoA reductase inhibitor
-
lipoprotein lipase
hydrolyzes FA from the chylomicrons into adipocytes
-
isocitrate DH
- - commited step of TCA (most important ez)
- - isocitrate--> alpha KG
- -first CO2 released, NADH produced
- - downregulated by NADH and ATP
-
PDH
- - pyruvate--> AcCoA
- - E1- inactivated by phosphorylation (T)
- - E2- inactivated by Ar (L,C)
- - E3- makes NADH (F,N)
-
aconitase
- - cis-aconitase--> isocitrate
- - inhibited by fluorocitrate
-
alpha KG DH
- -alpha KG--> succinyl CoA
- -TLCFN
- -succinyl CoA feedback inhibits
- - # ez complex, NOT controlled by phosphorylation
- - NADH inhibits
-
succinyl CoA sythetase
- succinyl CoA---> succinate
- - substrate level phosphorylation
-
citrate synthase
- - AcCoA+ozaloacetate-->citrate
- -irreversible
- - citrate can then down regulate PFK-1 except in the liver
- - ATP and NADH inhibit
-
glycerol phosphate shuttle
- - high activity in brain
- - NADH shuttles into Mt matrix via FADH2
-
malate aspartate shuttle
- high activity in liver and heart
-
complex 1 inhibitors
- -block e- flow from NADH to CoQ
- - rotenone
- - barbituates (amytal)
- - demerol
-
complex 3 inhibitors
Antimycin A
-
complex 4 inhibitors
- Cn, CO, H2S and azide
- - keeps Fe in 3+ state (prevents reduction, thus stopping e- flow)
-
uncoupling agents
- - 2,4 DNP, pentacholrophenol, high dose ASA, thermogenin
- -stimulate ETC, but bypass ATP synthetase
- - cause hyperthermia because all E is given off as heat instead of 50% used for ATP prod. and 50% to heat
-
oligomycin
ATP sythase inhibitor
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