BioChem Lec Quiz 9

Hydrocarbons have what water property?

Hydrophobic

Four fused rings form what?

Steroid nucleus

What is the cholesterol structure?

8 carbon branched hydrocarbon chain at C17 of D ring

Ring A- hydroxyl group at C3

Ring B- double bond between C5, C6

What is ring A?

Hydroxyl group at C3

What is ring B?

Double bond between C5, C6

What is the role of cholesterol?

Component of cell membranes

Modulates fluidity

What is cholesterol a precursor for?

Bile acids

Steroid horomones

Vitamin D

What are the two forms of cholesterol?

Free cholesterol

Cholesterol ester

What are the charactistics of free cholesterol?

30% exist in this form

Poorly soluble in water

Plasma membrane

What are the characteristics of cholesterol ester?

70% exists in this form

Less soluble in water than other form

Serum cholesterol

What are the different ways of esterfication of cholesterol?

Acyl-Coa: Cholesterol acyltransferase (ACAT)

Lecithin: Cholesterol acyltransferase (LCAT)

Phosphatidylcholine: Cholesterol acyltransferase (PCAT)

What ways do you increase cholesterol?

Dietary intake

De novo synthesis

What was do you decrease cholesterol?

Conversion to bile salts in liver

Excertion in bile

How much cholesterol in consumed in the western diet?

Around 0.5g cholesterol/day

What are sources of cholesterol in diet?

Meat, eggs, dairy

How much cholesterol is absorbed in the gut?

30-60%

How much cholesterol is made through De novo synthesis?

1g cholesterol/day

Where is cholesterol absorbed and secreted?

Intestines by specific transporters

What are the specific transporters for cholesterol?

Nieman-Pick C1-like protein (NPC1L1)

Chylomicrons

What is the role of chylomicrons?

Absorb dietary lipids at the enterocyte into the lymph vessels to be circulated through the body

What are chylomicrons?

Big ball of dietary lipids

Cholesterol, phospholipids, TAGs

What is the rate limiting enzyme/ step in cholesterol synthesis?

HMG-CoA Reductase

What decreases De Novo?

Statins

Red yeast rice

What do the statin drugs inhibit?

HMG-CoA Reductase

How does statin drugs inhibit HMG-CoA Reductase?

Lower cholesterol by binding to site of HMG-CoA on enzyme

What is the result of statin drugs inhibiting HMG-CoA Reductase?

Decreased intracellular cholesterol concentrations

Decrease in free cholesterol stimulates expression of LDL receptors

LDL clearance increases and plasma LDL-cholesterol decreases

Which part of the cholesterol is not broken down in humans?

Cholesterol ring

Which part of the cholesterol is eliminated from the body?

Sterioid nucleus

How is the steroid nucleus eliminated from the body?

Conversion of cholesterol to bile acid and bile salts

Secretion of free cholesterol into bile

What percentage of bile salts are excreted in feces?

Less than 5%

Where are bile salts reabsorbed?

Majority at ileum and return to liver via portal vein (enterohepatic circulation)

What are the primary bile acids synthesized by the liver?

7a-hydroxylase

Conjugated bile acids

Conjugation

What is 7a-hydroxylase?

Rate limiting step

What inhibits 7a-hydroxylase?

Bile acids (negative feedback)

What are the unconjugated bile acids?

Chenodeoxycholic acid

Cholic acid

During conjugation, what are bile acids conjugated with?

Taurine and glycine

Which bile acid is more is more ionized in GI lumen?

Conjugation over unconjugated (More effective detergents so they can bust up lipids)

What are the secondary bile salts?

Deoxycholic acid

Lithocholic acid

Where are bile salts produced?

Liver

Where are bile salts secreted?

Into bile

Where are bile salts stored?

Gallbladder

Where are bile salts released into during meal?

Intestines

What is the role of bile salts as a detergent?

Emulsify dietary lipids

What deconjugates and dehydroxylate the bile salts?

Intestinal bacteria

How does intestinal bacteria deconjugate and dehydroxylate the bile salts?

Remove glycine and taurine residues

Remove hydroxyl group at position 5

Which bile salts are less soluble and less readily absorbed?

Deconjugated and dehydroxylated bile salts

What bile-acid binding resin used to lower plasma cholesterol?

Cholestyramine (drug)

What is the function of cholestyramine?

Interrupts enterohepatic circulation of the bile acids

What is the physiology of taking cholestyramine?

Increase in 7a-hydroxylase activity —> increased bile acids synthesis —> Increased cholesterol excretion

What is cholesterol a precursor to?

All steroid hormones

What are the 3 groups of steroid hormones?

Corticosteroids

Androgens

Estrogens

Where are corticosteroids produced?

Adrenal cortex

Where are androgens produced?

Testes

Where are estrogens produced?

Ovaries

What is the rate limiting enzyme in steroidogenesis?

Desmolase

How are TAGs and cholesterol molecules transported in blood?

Lipoproteins

What makes up the core of lipoproteins?

TG and cholesterol esters

What makes up the surface of lipoproteins?

Phospholipids and free cholesterol

What are the Apoproteins of lipoproteins?

A, B, C, E

What is the big hylomicron?

B48

What cells assemble chylomicrons from dietary lipids?

Intestinal mucosal

What does intestinal mucosal cells contain for assembly of chylomicrons?

TG rich with some free cholesterol, cholesterol esters

Have apoB-48

What is obtained coming back from circulation to hepatocytes during assembly of chylomicrons?

apoC-II

apoE from HDL

During chylomicron degradation in peripheral tissue, what does apoC-II activate?

Lipoprotein lipase

What does LPL degreade?

Chylomicron triglycerides —> FA (released in peripheral tissue)

What happens to the chylomicron during degredation?

Becomes more dense (chylomicron remnant)

What are the contents of the chylomicron remnant?

Cholesterol ester rich, with some from cholesterol, and little TG

What are the chylomicron remnant taken up by?

Hepatocytes (liver) via apoE (key to liver)

What is VLDL most comprised of?

Triglycerides, with some cholesterol

Where is VLDL synthesized?

Liver, contain apo-B100

What does VLDL release obtain from HDL?

apoc-II and apoE

What occurs during VLDL degredation?

apoc-II activates lipoprotein lipase (LPL) in peripheral tissue

What is the physiology of VLDL degredation?

LPL degrades VLDL triglycerides —> FA (released in peripheral tissue)

What happens to VLDL during degredation?

Becomes more dense (IDL)

What happens to the IDL?

Can return to liver via apoE and metabolized by hepatic lipase

What is the IDL pathway?

IDL gains CE from HDL via cholesterol ester transfer protein (CETP) —> LDL

What does LDL contain?

High concentrations of cholesterol and CE

What is the function of the LDL pathway?

Deliever cholesterol to peripheral tissue via apoB-100

Where hepatic lipase found?

Found in liver

No LPL in liver

Where is HDL synthesized?

Liver and intestines

How is HDL released?

Protein rich particle

What does the HDL synthesis contain?

apoA-1 used to recover cholesterol from fatty streaks in vessels

What does HDL synthesis carry?

apoE and apoC-II to donate to chylomicrons

What is the pathway for HDL action on LCAT?

apoA-1 activates LCAT, PCAT —> produces cholesterol esters

What occurs during HDL action on LCAT?

HDl transports CE from peripheral vessels to liver

(Mopping up cholesterol)

What is the function of HDL cholesterol esters.

Donate CE to IDL via CETP

Or

Deliver CE to hepatocytes and steriogenic tissues via SR-B1

What different pathways can the liver acquire cholesterol?

De novo synthesis

Endocytosis of chylomicron remnants with residual dietary cholesterol

Transfer from HDL via SR-B1 receptor

Endocytosis of LDL

What is the function of hepatocytes endocytes LDL?

Hepatocytes contain LDL recpetors receptors (apoB-100) at cell membrane containing clathrin

LDL binds to receptor and is endocytosed (receptor mediated endocytosis)

What does the increased cholesterol levels intracellulary inhibit?

HMG-CoA Reductase

LDL- receptor gene expression

SR-B1 receptor gene expression

What does increased cholesterol levels intracellulary stimulate?

Acyl cholesterol acyl transferase

What is the function cholesterol esters produced?

CE stored in cells or converted to bile acids