Cholesterol metabolism

Question 1

what are the sources of cholesterol

what apoprotein mediates its interaction with hepactocytes?

Answer 1

1. dietary = chylomicron = chylomicron remnant = APO-E mediated uptake
2. de-novo synthesis
3. from circulating LDL = APO-B

Question 2

where is APO-E found

Answer 2

all lipoproteins - donated by HDL

Question 3

where is APO-B100 found

Answer 3

LDL, IDL, VLDL

Question 4

some names of bile acids/salts and

describe the synthesis of bile and its fates

Answer 4

name: cholic acids/ chenodeoxycholic acid
- they have pka of 6, same as duodenal ph = 50% ionised (amphipathic molecules)

• undergoes conjugation at hepatocyte
  > glycine (glyco-) & taurine (tauro-)
• gut flora can:
  > deconjugate
  > convert to secondary bile acids: DEHYDROXYLATED

Question 5

what are the uses of cholesterol in our body

Answer 5

synthesis: vitamin D precursor, bile acids, steroid hormones
structural: membrane synthesis and lipoprotein component

Question 6

describe the synthetic pathway of chlesterol

what are some regulatory factors

Answer 6

• HMG CoA —> mevalonic acid (HMG coA reductase, rate limited)
• positive regulartion: insulin and thyroxine
• negative regulation: glucagon and glucocorticoid
• ## cholesterol also exert negative feed back

Question 7

describe the fate of bile acids after its been released

Answer 7

• 95% recycled, at the ileum and returned into blood (bound to albumin), to the liver
• 3% made LOSS is FACEAS

NB increase bile acid loss leads to increased CHOLESTEROL demand (so hepatocytes will uptake more LDL from peripheral circulation, by expressing more LDL-receptors)
- beneficial as it reduced circulating LDL levels = reduce atherosclerosis risk

Question 8

what are the roles of HDL

Answer 8

• reverse cholesterol transport
  = take up cholesterol from peripheral tissues
  > ABCA1 and ABGA1 on tissue cells export cholesterol and HDL takes it up (nascent takes up ABCA1)
• donates APO-E and APO-CII to chylomicrons and VLDL for their function
• HDL can also deliver cholesterol to liver to use
  https: //www.google.com/search?q=does+HDL+deliver+cholesterol+to+liver&rlz=1C5CHFA_enGB821GB821&sxsrf=ALeKk03JsCDJSNAQLMg8y5bmQS2RXxG8RA:1587648495907&source=lnms&tbm=isch&sa=X&ved=2ahUKEwiFoIHF0_7oAhVaIqYKHf7zC-UQ_AUoAXoECA0QAw&biw=1232&bih=643#imgrc=2Gimu8F0b_HRVM

Question 9

where is HDL produced

Answer 9

LIVER AND INTESTINE

Question 10

what is tangier disease

Answer 10

deficient ABCA1 = no export of cholesterol to HDL = no need for HDL = DEFICIENT OF HDL PARTICLES