cholesterol (fri lecture) 3/3

Yeast

synthesize PC from PE via phosphatidylethanolamine acted on by SAM

Salvage pathway

synthesis of PS and PC in mammals constitutes a … where PS is made backwards from PE or PC via head group exchange reactions

Isoprene

important molecule for cholesterol synth, 5C unit

3

how many acetates condense in the formation of cholesterol

Acetate

3 of these condense to for cholesterol

Mevalonate

formed from the condensation of 3 acetates in the formation of cholesterol

5 c isoprene

mevalonate is converted to … when phosphorylated

6

how many isoprene’s (5C each) are polymerized to form the 30C linear sequence

Squalene

cyclized form of the 30C linear sequence of isoprene’s to form 4 rings that are modified to produce cholesterol

18 ATP

total cost of making cholesterol is …

HMG Coa

3 acetyl coa are condensed to form…

Reduced

HMG Coa is ___ to form mevalonate

NADPH

donates the electron used to reduce HMG coa to mevalonate

HMG coa synthase

enzymes that forms HMG coa from 3 acetyl coa

HMG coa reductase

enzyme that uses 2 NADPH to release a coaSh and form mevalonate

3

how many atp are used to transfer phosphates stepwise to ONE molecule of mevalonate

1 cholesterol

18 ATP and 6 isoprene units are used to make …

Double bond

an activated isoprene has a …

Decarboxylation and hydrolysis

reaction type which creates dephosphorylated activated isoprenes

Geranyl pyrophosphotase

joins another isoprene onto the chain of 2 isoprenes HEAD TO TAIL to make 15 C farnesyl pyrophosphate

Squalene synthase

use 2 units of farnesyl pyrophosphate, join them head to head to form squalene (30C)

Cyclase

in animals this enzyme converts squalene to cholesterol through a multistep sequence, divergent from pathway in plants and fungi

Liver

in vertebrates most cholesterol is synthesized in the…

Bile acid, biliary cholesterol or cholesteryl esters

cholesterol is exported from the liver as… in most vertebrates

Gallbladder

bile is stored in the … before being secreted to the small intestine following a fatty meal

Cylomicrons

the biggest lipoprotein particles (mostly TAGs), least dense, contain apoB 48, apoE, apoC II, take dietary fat to body

Very low density lipoprotein

contains TAG and cholesteryl esters in high concentrations, contain apoB 100, apoCI and apoC II, apoE

Low density lipoprotein

made by removal of TAG from VLDL, enriched in cholesterol/cholesteryl esters, apoB 100 major apolipoprotein

High density lipoprotein

smallest diameter, made from enzymatic conversion of LDL and VLDL cholesterol to cholesteryl esters, high in protein esp apoA I

apoC II

activates lipoprotein lipase to allow FFA release for fuel in adipose tissue, heart and skeletal muscle, when fats are depleted remnants go to liver in chylomicrons and VLDL

apoB100

muscle and adipose tissue receptors for LDL’s

receptor mediated endocytosis

cellular level cholesterol uptake by…

lecithin cholesterol acyl transferase (LCAT)

enzyme for the conversion of phosphatidylcholine (lecithin) to cholesteryl ester and lysolecithin inside of apolipoproteins

HMG Coa reductase

highly regulated step in cholesterol metabolism (enzyme)

Insulin

upregulates HMG coa Reductase which makes cholesterol

Glucagon and low ATP

down regulates HMG coa Reductase to stop making cholesterol

Dephosphorylated

HMG coa reductase is most active when _____

AMPK

will phosphorylate HMG coa reductase and reduce activity and therefore cholesterol synthesis, during times of AMP levels that are HIGH

Covalent

type of mechanism that is phosphorylation regulation of HMG coa reductase

Short term

covalent phosphorylation regulation of HMG coa reductase is ….

Insulin

leads to dephosphorylation of HMG coa reductase (hormone)

Glucagon, epinephrine

leads to phosphorylation of HMG coa reductase (hormone)

Gene control

long term regulation of HMG coa reductase via …

SREBP

activates transcription of HMG coa reductase when sterol levels drops this transports to the nucleus to act as a transcription factor

Insig

bound to oxysterol during high cholesterol levels, prevents transport of SREBP to nucleus, in low levels, upiquition binds and releases SREBP to the nucleus to transcribe HMG coa reductase

LXR

transcription factor activated by cholesterol that forms a herterodimer with RXR

LXR RXR

activates the transcription of cholesterol synth genes

High HDL, low LDL

a healthy persons cholesterol types/levels would be…

Monocyte, macrophage, foam cell

formation of plaques in blood vessels pathway

Statin

drug that inhibits hmg coa reductase to lower cholesterol synthesis as it resemble mevalonate and acts as a competitive inhibitors, 1st found in fungi DON’T USE WHILE PREGO

HDL

can reverse pick up cholesterol from non liver tissue including foam cells at growing plaques, and bring cholesterol back to the liver… which explains why it is cardioprotective

Mineralocorticoids and glucocorticoids

adrenal gland synthesized steroids derived from cholesterol

Progesterone, androgens, estrogens

gonad synthesized steroids derived from cholesterol

NADPH

the conversion from cholesterol to pregnenolone requires…