Cholesterol, Lipid Digest/absorb,lipoprotein Metab

Front 1

HMG CoA Reductase

Back 1

Catalyzes the rate-limiting step in cholesterol biosynthesis.

The target for statins.

Front 2

Isoprene (Isoprenoids)

Back 2

Isoprene is a precursor molecule to many things, including dolichol, CoenzymeQ, Vitamin A, and Vitamin E

Its synthesis is also blocked by statins..

Front 3

What are some uses for cholesterol?

Back 3

Membrane constituent, precursor to bile acids, steroid hormones, and Vitamin D.

Front 4

Cholesteryl Ester

Back 4

an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Cholesteryl Esters have a lower solubility in water than Cholesterol and, in other words, are more hydrophobic. <b>They are associated with atherosclerosis.</b>

Front 5

What is the ultimate precursor to cholesterol?

Back 5

Acetic acid

Front 6

First step in cholesterol synthesis?

Back 6

Acetyl CoA to acetoacetyl CoA via thiolase.

Front 7

Thiolase

Back 7

Converts acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. (1st step in cholesterol synth)

Front 8

HMG CoA Synthase

Back 8

Converts acetoacetyl CoA into 3OH3CH3glutarylCoA (similar to ketogenesis)

2nd step in cholesterol synth

Front 9

1st committed step in cholesterol synthesis

Back 9

HMG CoA Reductase converts intermediate to mevalonic acid.

Rate-limiting step.

takes carboxylic ester (the intermediate) and converts it to an alcohol (mevalonic acid/mevalonate) using NADPH

Front 10

What happens after mevalonic acid is created?

Back 10

The molecule gets phosphorylated 3 times. This molecule is unstable and doesn't stick around very long.

Front 11

Overall general idea of cholesterol biosynthesis

Back 11

A) Acetyl CoA --> HMG CoA
(HMG CoA synthase)

B) HMG-CoA --> mevalonate
RATE LIMITING STEP!!!
HGM-CoA Reductase

C) Basic 5 carbon building block: mevalonate --> isopentenyl PP

D) Polymerization (5C->10C->15C->30C)

E) Cyclization (squalene to lanosterol)

F) Sterol modification (lanosterol --> cholesterol)

Front 12

What is the first steroid in the pathway?

Back 12

Linosterol

It's even more atherosclerotic than cholesterol!

Front 13

How is HMG CoA Reductase regulated?

Back 13

1) Feedback regulation of its turnover: oxysterol-INSIG binding to HMGCoA-R activates proteolytic cleavage of HMG-CoA Reductase.

2) Transcriptional Regulation: The level of membrane cholesterol is regulated by SREBP2.
SREBP2 migration induces transcription.

Cholesterol presence and oxysterol-INSIG binding prevent SREBP2 migration.

Insulin promotes migration by binding to INSIG and promoting dissociation

5) Phosphorylation inactivates HMG Co-A

Front 14

How statins work

Back 14

They don't JUST inhibit production of cholesterol.

When there is less cholesterol released from liver, the LDL receptors are upregulated, resulting in MORE LDL being taken up by cells and out of blood.

Front 15

Pancreatic lipase (and colipase)

Back 15

Hydrolyzes ester bonds of triglyceride to produce free fatty acid and 2 monoglycerol (leaves one fatty acid on)

Requires colipase

Front 16

Bile

Back 16

1) Made in the liver and stored/concentrat
ed in gallbladder.


2) Is a mix of bile salts, phospholipids, and cholesterol stabilized in micelles and other aggregate structures.

3) Has a polar face and a hydrophobic ring system. Because of this it's detergent by nature.

Front 17

Gallstones

Back 17

Form when supersaturated biliary cholesterol precipitates.

Can occlude the bile duct and prevent emptying of the gallbladder and passage of bile from liver.

Front 18

Common bile duct

Back 18

Is a transport duct for bile from liver (from gallbladder) and pancreatic juice from pancreas.

Front 19

What is the main purpose of micelles?

Back 19

Coats fat coming in from stomach, increases surface area.

Coat surface – stabilize fat droplets, disperse the lipids somewhat

Front 20

What do bile salts do?

Back 20

Coat surface of the fat droplets. They activate lipase. The promote product removal.

Front 21

Cholesteryl ester hydrolase

Back 21

Breaks cholesteryl ester into cholesterol and oleic acid/oleate

Front 22

Enterocytes

Back 22

Cells lining the small intestine, they absorb things (fats by active transport)

Lipids are broken down by pancreatic lipase and bile, and then diffuse into the enterocytes. Smaller lipids are transported into intestinal capillaries, while larger lipids are processed by the Golgi and smooth endoplasmic reticulum into lipoprotein chylomicra and exocytozed into lacteals.

Front 23

Lacteal

Back 23

lymphatic capillary that absorbs dietary fats in the villi of the small intestine.

These merge to form the thoracic duct, which drops its contents into the subclavian vein.

Front 24

chylomicrons

Back 24

One of the 5 major lipoproteins.

Formed after fat is transported into enterocytes.

Contains Apo A, B, C, and E proteins in addition to triglycerides, cholesterol, and phospholipid.

<b> Their purpose is to transport fats to other parts of body through blood. </b>

Front 25

Trace the path of chylomicrons

Back 25

Formed in the enterocytes --> released into lacteals --> bloodstream

Front 26

Does most cholesterol in the body come from dietary cholesterol?

Back 26

NO. Most of it is made bythe body. Dietary cholesterol is only fractionally absorbed.

Front 27

What is the difference in transport by short, medium, and long chain fatty acids?

Back 27

Short and medium chain (C<12) diffuse into the portal system and are transported via albumin.

Long chain are broken down by bile/lipase, resynthesized into triglycerides, and incorporated into chylomicrons which is the way they're transported by the body.

Front 28

Niemann-Pick C1 Like 1 (NPC1L1)

Back 28

protein localized in jejunal enterocytes that is critical for intestinal cholesterol absorption.

drug Ezetimibe inhibits.

Front 29

Enterohepatic Circulation of Cholesterol

Back 29

refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver.

Front 30

Why are medium chain fatty acids good to use in people with impaired digestive function?

Back 30

1) More easily broken down by pancreatic lipase. (better substrates)

2) Can be infused parenterally (totally bypassing digestive system)

3) Do not go through the carnitine shuttle, so they're more easily B-oxidized.

Front 31

Cholestyramine

Back 31

bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption in the ileum.

(>95% of bile salts are normally resorbed via portal system)