Biochem Lec 3 - Lipid Metabolism - Cholesterol and steroid metabolism Flashcards
cholesterol is a what alcohol
steroid alcohol
function of cholesterol
-structrual component of membranes, modulating fluidity
-precursor of bile acids, steroid hormones and vitamin D
what organ plays a central role in cholesterol regluation
liver
choelsterol enters the liver from
-diet
-cholesterol synthesized de novo by the liver
-extrahepatic tissues
cholesterol is eliminated from the liver as
-unmodified cholesterol in the bile
-converted to bile salts that are secreted into intestinal lumen
-secreted as VLDL
structure of cholesterol
-4 fused hydrocarbon rings w a 8 acrbon, branched hydrocarbon chain attached to carbon 17 of the D ring
cholesteryl esters structure
esterified form (w a FA attached at carbon 3)
sterols structure
steroids w a 8-10 carbon, branched hydrocarbon chain attached to carbon 17 of the D ring and OH group at carbon 3 on ring A
cholesterol is synthesized by virtuall all tissues in humans, but what are the largest contributors
-liver
-intestine
-adrenal cortex
-reproductive tissues, including ovaries, testes, and placenta
synthesis of cholesterol phases
conversion of acetyl CoA to HMG-CoA
conversion of HMG-CoA to squalene
conversion of squalene to cholesterol
what is the rate limiting product in the second step of cholesterol synthesis
mevalonate - the rate limiting product
what is the enzyme for the second step of cholesterol synthesis (conversion of HMG-CoA to squalene)
HMG-CoA reductase is the key enzyme for cholesterol synthesis
what is statins
most common cholesterol lowering drugs (inhibits HMG-CoA reductase
what does cholesterol do
inhibits the reductase and catalyzes its breakdown
what cannot be metabolized to CO2 and H2O in humans
ring structure of cholesterol
how are intact sterol nucleus eliminated from the body
eliminated from the body by conversion to bile acids and bile salts in the liver
how are bile/salts synthesized
by cholesterol
where is bile produced and stored
bile produced in the liver, stored in the gallbladder
bile is water soluble so it can be excreted
bile can pass directly from the liver to where
to the intestine or stored in the gall bladder
what does bile help w
helps emulsify fats and fat soluble vitamins thereby aiding absorption
what enzyme is the rate-limiting step in bile acid synthesis (cholesterol degradation)
cholesterol 7-alpha hydroxylase catalyzes the rate liminating step in bile acid synthesis (modifies structure)
before bile acids leave the liver
they are conjugated to a molecule of either glycine or tuarine
cholesterol and other steroids are derivatized to
improve solubility and are excreted in solution
cholesterol is converted to bile acids and then what and where
and then bile salts in the liver
bile contains
bile salts, cholesterol, phospholipids, and bile pigments (bilirubin [yellow] and biliverdin [green])
the yellow-green bile is produced by what and stored where
produced by hepatocytes
stored in the gall bladder
bile helps do what
emulsify fats and fat soluable vitamins, thereby aiding in absorption
almost all (>95%) the bile salts secreted into the intestine are reabsorbed where and reused
small intestine
smaller percent is lost in feces
what are lipoproteins
spherical macromolecular complexes of lipids and specific proteins (apolipoprotein or apoproteins)
lipoprotein particules include
chylomicrons (CM)
very low density lipoproteins (VLDL)
low density lipoproteins (LDL)
high density lipoproteins (HDL)
how do lipoproteins differ
differ in lipid and protein composition
density is a ratio of protein: lipid composition
function of lipoproteins
function in lipid transport
chylomicron function
transport lipids from intestine to peripheral tissues
where are chylomicrons assembled
assmebled in the intestine
VLDL (very low density lipoprotein) production site
produced in liver
VLDL function
transports lipids from liver to peripheral tissues
what happens when VLDL gets depleted?
they become LDLs
LDL function
transport cholesterol to issues
“bad cholesterol”
LDL
“good cholestero”
HDL
HDL function
transports cholesterol from peripheral tissues to the liver
cholesterol plaques lead to
artherosclerosis
why is LDL bad
consist of core cholesterol esterified to fatty acids and a protein/cholesterol coat
LDLs deposit cholesterol in the arteries
why is HDL good
transports cholesterol to the liver for the conversion to bile acids and for disposal
cholesterol is a precursor of all classes of what
steroid hormones (glucocorticords (cortisol), mineralocorticoids (aldosterone), and sex hormones (androgens, estrogens, progestins)
synthesis and secretion of steroid hormones occur in
adrenal cortex (cortisol, aldosterone, and androgens)
ovaraies and placenta (estrogens and progestins)
testes (testosterone)
how are steroid hormones transported
by blood from site of synthesis to target organs
why must steroid hormones be complexed with a plasma protein
bc of their hydrophobicity
steroid hormone sequence
cholesterol -> pregnenolone -> progesterone
