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FoundSci Unit 4 > Cholesterol & Phospholipids > Flashcards

Cholesterol & Phospholipids Flashcards

1
Q

Hypercholesterolemia

A

High LDL (“bad cholesterol”) raises Cardiovascular disease risk

Primary hypercholesterolemia - genetic defect and presents in infancy

Secondary hypercholesterolemia - presents in adulthood because of sedentary lifestyle, cholesterol rich diet, and smoking

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2
Q

How much cholesterol in the body is synthesized in the liver?

A

Half

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3
Q

What drugs can lower LDL cholesterol by inhibiting endogenous cholesterol synthesis. How?

A

Statins. They inhibit HMG-CoA reductase that produces cholesterol

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4
Q

What is good about cholesterol?

A

Modulates membrane fluidity and membrane protein activity

Substrate for steroid hormone synthesis in skin and endocrine tissues

Substrate for synthesis of emulsifier for dietary fat in the liver –> bile

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5
Q

Why is too much cholesterol bad?

A

Excess LDL is taken up by macrophages and seeds plaques in blood vessels which predisposes someone to cardiovascular disease

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6
Q

When and where is cholesterol made?

A

Made in liver during the fed state

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7
Q

What is cholesterol?

A

Isoprenoid - not a fatty acid or a carb

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8
Q

How is cholesterol synthesized?

A

Isoprenoid synthesis begins with acetyl-CoA

Begins with condensation reaction of 3 acetyl-CoA molecules to hydroxymethyglutaryl-CoA

HMG-CoA is then converted to mevalonic acid by HMG-CoA reductase

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9
Q

What is the committed step of cholesterol synthesis?

A

HMG-CoA reductase

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10
Q

What does HMG-CoA reductase yield?

A

Isoprenoids (cholesterol)

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11
Q

What does HMG-CoA lyase yield?

A

Ketone bodies

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12
Q

What regulates HMG-CoA reductase?

A
  1. Phosphorylation - AMPK activates in response to low energy
  2. Protein expression (insulin/glucagon) - insulin increases protein amounts and glucagon decreases
  3. Inhibited by statin drugs and cholesterol

Inactive in fasting or low energy state

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13
Q

What happens after HMG-CoA reductase produces mevalonic acid?

A

Mevalonic acid converted into dimethylallyl PP and isopentenyl PP (5 carbons each)

Two dimethyallyl PP and one isopentenyl PP make farnesyl pyrophosphate (15 carbons)

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14
Q

What is farnesyl PP an important precursor for?

A

Coenzyme Q for e- transport

Dolichol phosphate for protein glycosylation

Lipid anchor for peripheral membrane proteins

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15
Q

What occurs with insufficient cholesterol synthesis?

A

Affects electron transport and post-translational protein modification

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16
Q

How is farnesyl PP converted to cholesterol?

A

2 farnesyl PP are condensed to form squalene and then intramolecular rearrangements produce lanosterol (30 carbons)

Cholesterol (27 carbons) results from enzymatic modifications of lanosterol

17
Q

Explain the process of storing cholesterol

A

Cells acquire cholesteryl esters (CE) from LDL by receptor mediated endocytosis

LDL digested in lysosome and cholesterol released into cytosol

LDL receptor recycled to the surface

Acyl-CoA cholesteryl acyltransferase produces cholesteryl ester for storage in droplets

Lipid droplets contain cholesteryl esterase for eventual cholesterol release

18
Q

What does it mean for a cell if they have more LDL receptors?

A

Higher uptake of cholesterol esters from LDL

19
Q

What do drugs for lower cholesterol also target in relation to LDL?

A

LDL receptor cycling so that more cholesterol is not stored

20
Q

What types of cells have lots of acyl-CoA cholesteryl acyltransferase?

A

Steroid hormone producing cells

21
Q

Explain the process of excreting cholesterol

A

Two step reaction - increases amphipathic properties

  1. Cholesterol converted to 7alpha-Hydroxycholesterol by 7alpha-hydroxylase
  2. Addition of taurine or glycine that forms primary bile acids in gall bladder
22
Q

What are bile acids?

A

Bile acids are produced by the liver to emulsify dietary fat and they break up big drop to give access to lipases

23
Q

After 7apha-hydroxycholesterol is converted to chenodeoxycholic acid or cholic acid. Taurine or glycine is added. What are the products when taurine or glycine is added? What happens to them?

A

Addition of taurine - Taurochenodeoxycholic acid or taurocholic acid

Addition of glycine - glycochenodeoxycholic acid or glycocholic acid

These are the primary bile acids in gallbladder and they are secreted in bile together with cholesterol, phospholipids, fatty acids, and salt

They are then modified and taken up to form the secondary bile acids in the gut, which re-enter through enterohepatic circulation

24
Q

Secondary Bile Acids

A

Bile acids that are taken up through enterohepatic circulation and can act as steroid hormones

In the liver and intestinal cells, bile acids bind to farnesoid X receptor (FXR) and inhibit fatty acid synthesis via steroid response element binding protein (SREBP1)

25
Q

What does FXR signaling inhibit?

A

Bile acid production

26
Q

What does the microbiome have to do with bile acids?

A

Microbiome can produce secondary bile acids with different hormonal activities. Gut microbes affect host gene expression

27
Q

What is going on with a patient who present with sharp pain in upper right quadrant and nausea? Pt also has jaundice elevated serum bilirubin, and elevated alkaline phosphatase.

A

Indicate cholestasis (gall stones) and bilirubin and alkaline phosphatase not secreted into gut

28
Q

What causes gall stones?

A

Gall fluid contains cholesterol, bile acids, phospholipids, and bilirubin

Cholesterol in bile is close to precipitation point so small changes in bile secretion or bile metabolism can produce cholesterol stones in bile. Not as common is precipitation of bilirubin

Can be treated with ursodeoxycholic acid to dissolve stones

29
Q

What do the bulk of biomembranes consist of?

A

Phospholipids - two fatty acids and a phosphate containing polar head on a glycerol backbone

30
Q

What are the lipids common in different membranes?

A

Phospholipids - Phosphatidylcholine (PC), Phosphatidylethanolamine (PE), Phosphatidylinositol (PI), Phosphatidylserine (PS), and cardiolipin (CL)

Cholesterol - CHOL

Sphingolipids - SM

31
Q

What is the lipid composition of the plasma membrane and mitochondrial membrane?

A

Plasma membrane is rich in sphingolipids, cholesterol and plasmologens. Has lipids with signaling function

Mitochondrial membranes are rich in cardiolipin

32
Q

How are phospholipids synthesized?

A

Begin with phosphatidic acid

Activation of one of the components by binding to a CTP nucelotide

PI and Cardiolipin syntehsized from activated Diacyl Glycerol

PC, PE, and PS are synthesized from activated choline/ethanoalamine

33
Q

What is the role of CTP in phospholipid synthesis?

A

PI and cardiolipin - CDP binding used to activate the lipid DAH

PC and PE - CDP binding used to activate the head group

34
Q

Explain synthesis of cardiolipin and phosphatidylserine

A

Inner mitochondrial membrane is rich in cardiolipin - two phosphatidic acids connected with glycerol

PS made from PC or PE via head group exchange or carboxylation. PE +serine -> PS + ethanolamine. PC + serine -> PS + choline

FoundSci Unit 4 (11 decks)

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