Ch 18

Cholesterol synthesis and steroid metabolism

cholesterol makes up a large part of/most of what part of cells?

the membrane

cholesterol is a precursor of what molecules in the body?

vitamin D,

bile + bile salts,

steroid hormones

what organs of the body have high levels of cholesterol synthesis?

LIVER,

reproductive system,

intestines,

adrenal cortex

3 major sources of cholesterol in the liver

de novo/cholesterol synthesized in liver,

through diet from chylomicrons,

extra hepatic tissue (as LDL, HDL)

how is cholesterol eliminated from the liver?

excreted unmodified in bile,

eliminated as VLDL,

converted to bile salts

is cholesterol influx← → efflux tightly regulated in humans?

what can this cause?

no;

can cause atherosclerosis

if there is too much cholesterol in the body, where does it deposit (when not eliminated)?

in blood vessels

what is the overall structure of cholesterol?

where are the substituent groups located?

4 fused carbon rings with:

• OH group on C3

• double bond from C5 to C6

• hydrocarbon tail attached to C17

how long is the hydrocarbon tail on cholesterol?

8 carbons long

what type of rxns happen on the substituents of cholesterol?

esterification,

redox

all C atoms in cholesterol come from what molecule?

acetate

what supplies reducing equivalents for cholesterol synthesis?

NADPH

is cholesterol synthesis endergonic or exergonic?

endergonic

what supplies energy for synthesis of cholesterol?

hydrolysis of ATP and acetyl CoA

where does cholesterol synthesis occur?

in cytoplasm,

in endoplasmic reticulum

what are the first two steps in cholesterol synthesis?

1. 2 acetyl CoA → HMG-CoA by reduction

2. HMG-CoA → mevalonic acid through reduction by NADPH

where does reduction of HMG-CoA by NADPH occur?

in the endoplasmic reticulum

what forms after mevalonate/mevalonic acid (until cholesterol is formed)?

IPP,

squalene,

lanesterol,

cholesterol

3 ways cholesterol synthesis is regulated?

product inhibition,

short-term hormonally,

long-term

what is inhibited in allosteric regulation of cholesterol synthesis? how?

HMG-CoA reductase by:

• cholesterol allosterically

• drugs (like statins) reversibly

HMG-CoA reductase phosphorylation is ___-term regulation that is reversible or irreversible?

short-term hormonal regulation;

reversible

is HMG-CoA reductase active or inactive when phosphorylated?

inactive

what molecule is the fundamental building block of the sterol ring?

mevalonic acid