Biochemistry Exam Ii - Lipids

Front 1

- Energy (oxidation of fatty acids in liver and muscle)
- Membranes (separation of cellular components)
- Regulation (steroids, prostaglandins, many other bioactive molecules)
- Detergents (solubilize nonpolar substances in body fluids)

Back 1

Functions of fatty acids

Front 2

Most common unsaturated fat is ______

Back 2

Oleic acid 18:1 delta 9

Double bond between 9 and 10

Nine carbons away from omega carbon

Front 3

- Increases with chain length
- Decreases with double bonds

Back 3

Melting point

Double bonds trump chain length

Front 4

Alpha-linoleic acid (omega-3) 18:3 d9,12,15

Linoleic Acid (omega-6). 18:2 d9,12

Arachidonic Acid (omega-6) 20:4 d5,8,11,14

Back 4

Essential fatty acids.

Cannot make de novo

Front 5

Fatty acid molecule in thioester linkage with CoA molecule

Back 5

Fatty Acyl CoA

Front 6

No charge on this molecule

We store them in the body

Digested by lipases

Back 6

Triacylglycerols

Lipase cleavage = DAG + FFA

Front 7

- Phosphatidylcholine
- Phosphatidylethanolamine
- Phosphatidylserine
- Phosphaditylinositol
- Cardiolipin

Back 7

Major phospholipids

Components of cellular membranes.

Front 8

Composes 30% of inner mitochondrial matrix.

Polar head group is in the middle of this molecule

Back 8

Cardiolipin

Front 9

When a molecule has polar and nonpolar parts.

One part soluble in water, one part solule in lipid

Back 9

Amphipathic molecule

Front 10

Phospholipases are mostly under hormonal control.

Arachadonic acid is precursor for _______________ production

Back 10

prostaglandin

Front 11

-Derived from serine and palmitic acid
- Different, nonglycerol backbone
- Attach things to OH

Back 11

Ceramide

Front 12

- Sugar acid
- Negatively charged
- Ceramide based

Back 12

NANA

Front 13

- Has OH at C3

- Allows for interaction with aqueous environment

- If lost, becomes very hydrophobic

Back 13

Cholesterol

Front 14

- Adipose tissue
- Liver
- Mammary tissue

Back 14

Major sites of lipid synthesis

Don't store fat in liver or mammary gland

Fatty acid synthesis begins with glucose entering the cell.

Front 15

- Cytosol
- Acetyl CoA
- ATP and Mg2+
- HCO3-
- Citrate
- NADPH

Back 15

Requirements for fatty acid synthesis

Front 16

Of the following, which enzyme belongs in the committed step of Fatty Acid Synthesis:

- Malonyl CoA carboxylase
- Pyruvate carboxylase
- Acetyl-CoA carboxylase
- Fatty acid synthetase

Back 16

- Acetyl-CoA carboxylase

Cofactors:
- Citrate
- Mg2+
- ATP
- HCO3-
- Biotin

Turns Acetyl-CoA into Malonyl-CoA

Front 17

1 palmitate + 7 CO2 + 14 NADP+ + 8 CoA + 6 H20

Back 17

Products of Fatty Acid Synthase

Front 18

Regulation:

Acetyl-CoA Carboxylase (CBX)

Back 18

Stimulated by:
- Insulin
- Dephosphorylation (by insulin)
- Decreased ratio of AMP/ATP
- Citrate
Inhibited by:
- Long chain fatty acyl-CoA's
- Fats from diet
- Increased ratio of AMP/ATP
- Phosphorylation (by AMP activated protein kinase (AMPK)
- Epinephrine and glucagon
- Malonyl CoA

Front 19

What affects the citrate transporter?

Back 19

Stimulates:
- High levels of ATP (slows down the TCA cycle - citrate pumped out of mitochondria)

Inhibits:
- Fatty Acyl CoA

Front 20

What neurotransmitter is a potent stimulator of appetite?

Back 20

Neuropeptide-Y

NPY

Front 21

Inhibition of what enzyme on the Fatty Acid Synthase protein has been shown to control feeding regulation?

Back 21

Condensing enzyme

Build up of malonyl CoA is though to be the signal which inhibits NPY secretion

Front 22

A molecule that inhibits pancreatic lipase should also be expected to inhibit what enzyme?

Back 22

Condensing enzyme on Fatty Acid Synthase

Front 23

Inhibition of the condensing enzyme of Fatty Acid Synthase did not tend to make people lose weight. What effect did it have?

Back 23

Improved lung cancer survival

Front 24

1) Generate a glycerol phosphate backbone

2) Generate phosphatidic acid by esterification of fatty acids to position 1 and 2

3) Generate a DAG by removal of the phosphate from position 3

4) Generate a TAG by esterification of a fatty acid to position 3

Back 24

Synthesis of TAGs

Glycerol kinase phosphorylates glycerol to glycerol-3-phosphate (absent in adipose tissue)

Front 25

The first step of TAG synthesis occurs in all tissues.

These intermediates are from what pathway?
- DHAP
- NADH
- G3P

Back 25

Glycolysis

Phosphatidic acid and DAG are used in intermediates in other pathways too

Front 26

In this tissue, most TAGs are from diet or synthesized by the liver

Back 26

adipose

Mammary tissue and liver produce fat de novo

Front 27

This type of fat has the following characteristics:

- Lots of mitochondria
- Expression of uncoupling protein
- Uncouples ETC, generates non-shivering heat

Back 27

Brown adipose

Found in infants in the infrascapular region.

Adults: cervical, supraclavicular and paravertebral depots

Other sites listed: Retro-orbical, Periarticular regions, bone marrow, intramuscular, pericardial

Front 28

Name the fat depot

- Higher basal and stimulated adenylate cyclas activity
- Higher LPL activity
- Lipolysis not suprressed by insulin
- Greater lipid flux
- Drain into the portal venous system, Non-esterified fatty acids (NEFA's) are transported to the liver = stimulates hepatic GNG

Back 28

Intra-abdominal fat

Common sites:

Omental
Retroperitoneal
Visceral

Front 29

Name the fat depot

- Enhanced lipid storage
- Lipolysis suppressed by insulin
- Insulin receptor, GLUT4, leptin and PPARy all expressed at higher levels than omental
- Depots drain into the systemic venous system and NEFAs are distributed around the body.
- Preadipocytes differentiate more readily

Back 29

Subcutaneous

Common sites:
- Crainal
- Facial
- Abdominal
- Gluteal

Front 30

a protein hormone produced by adipose tissue.

Its concentration in the body provides the brain with a rough indication of adipose mass for the purposes of regulating appatite and metabolism.

Back 30

Leptin

Front 31

Secretion by adipocytes is directly proportional to adiposity.

Stimulates recruitment of additional macrophages to adipose tissue.

Back 31

Macrophage Chemo-attractant Protein1 (MCP1)

Front 32

Secreted by adipocytes as well as macrophages in the tissue in proportion to adiposity.

TNFα is a cytokine involved in the inflammatory response.

Back 32

Tumor necrosis factor α (TNFα)

Regulates immune system

Front 33

Synthesized & secreted by adipose tissue.

Promotes/controls insulin sensitivity.

Back 33

Adiponectin

Front 34

Synthesized & secreted by adipose tissue.

Promotes/controls insulin resistance.

Back 34

Resistin

Front 35

This molecule is orexigenic (promotes increased energy intake).

Levels are decreased with increased levels of leptin

Back 35

Neuropeptide Y

Most potent appatite stimulator

Front 36

Leptin binds to the arcuate nucleus in the hypothalmus...what affect on NPY stimulation does it have?

Back 36

Decreases NPY stimulation

Stimulates POMC neuron (leads to secretion of a-MSH), which bind to receptors that signal satiety

Front 37

Preopiomelanocortin (POMC) is the precursor to the _____________ which bind to receptors and signal satiety

Back 37

melanocortins

Specifically, alpha-melanocyte stimulating hormone (a-MSH)

Front 38

This deficiency does the following:

- Drives hunger
- Suppresses energy expenditure
- Inhibits reproductive competance

Back 38

Leptin deficiency

Front 39

A deficiency in this receptor will not allow for fat synthesis

Back 39

Proxisomal proliferator activated receptor y (PPARy)

Target of thiazolidinedione drugs/glitazones

Front 40

What type of drugs are these?

- Actos (pioglitazone)
- Avandia (rosiglitazone)

They target the PPARy receptor.

Back 40

Thiazolidinedione drugs - glitazones

Move glucose out of the blood supply and into the adipocytes.

Concern is for toxic levels of glucose, not obesity

Front 41

- Fasting
- Prolonged exercise
- Diabetes (Type I predominantly)
- Sudden drop in environmental temperature
- Trauma/Stress

Back 41

Conditions promoting lipolysis

Front 42

Hydrolysis by HSL is the rate limited step for what reaction

Back 42

Lipolysis

Front 43

Albumin binds how many free fatty acids?

Back 43

one

Front 44

Oxidation of TAG's is dependeon on serum levels of what carrier molecule?

Back 44

Albumin

1 albumin molecule carries 1 FFA

Front 45

Malonyl CoA's role in TAG breakdown

Is malonyl CoA a product of lipolysis or FA synthesis?

Back 45

Inhibits CPT-1

Malonyl-CoA is a product of fatty-acid synthesis.

Result: Do not want to make fat while breaking it down (futile cycle)

Front 46

Fatty acids can by pass the carnithine system. It has to be less than how many carbons long?

Back 46

Less than 12 carbons long

Useful therapy for various disease states where CPT-1 or CPT-2 are deficient

Front 47

- Oxidation (FADH2 produced)
- Hydration
- Oxidation (NADH produced)
- Thiolase

Back 47

Steps of even chain Fatty Acid Oxidation in the matrix of mitochondria

Front 48

- Fatty Acyl CoA (FADH2 produced)
- Trans d2 enoyl-CoA
- B-Hydroxy acyl CoA (NADH produced)
- B-Keto acyl CoA
= Products (FA CoA + acetyl CoA)

Back 48

Products of even chain Fatty acid oxidation in matrix of mitochondria

Front 49

- Rate of fatty acid delivery to the tissue (albumin levels)

- rate of fatty acyl translocation across the inner mitochondria matrix (carnithine levels)

Back 49

Rate of B-oxidation is determined

Front 50

- Isomerase
- Hydration
- Oxidation (NADH produced)
- Thiolase

Back 50

Steps of odd-chain fatty acid oxidation in matrix of mitochondria.

Note: FADH2 not produced, thus, yields less energy

Front 51

- cis d2 enoyl CoA
- trans d2 enoyl CoA
- B-hydroxy acyl-CoA
- B-keto acyl-CoA
Products (FA CoA + acetyl-CoA)

Back 51

Products of odd-chain fatty acid oxidation

Front 52

Final process of odd-chain fatty acid oxidation.

Priopionyl CoA -> Methyl Malonyl CoA

Methyl Malonyl CoA -> Succinyl CoA

Succinyl CoA -> TCA

Back 52

First reaction is a carboxylation reaction (needs biotin, ATP, HCO3-)

Second reaction is a mutase that requires vitamin B12

Front 53

8 Acetyl CoA + AMP + PPi + 7 NADH + 7 H+ + 7 FADH2

Total: 106 ATP produced

How many are lost due to activation?

Back 53

1 is lost for ATP activation
1 is lost for PPi activation

Net = 108 ATP

Front 54

Acetyl-CoA levels when carbohydrate and fat breakdown is balanced:

1 mL/dL in circulation

Back 54

When fat breakdown preddominates, AcCoA is in excess and carbohydrates are unavailable or not properly utilized.

Decreased concentration of OAA

Ketogenesis predominates

Front 55

- Elevated gluconeogenesis
- Increased delivery of fatty acids to liver
- Increased ketogenesis
- Ketone spillage to urine

Back 55

Metabolic consequences of ketogenesis

Hormones: decreased insulin, increased glucagon

Front 56

50 um after a meal
200-400 um after an overnight fast
1-2 mM after a three day fast
6-8 plateau upon prolonged starvation

Back 56

Serum concentrations of beta-Hydroxy Butryate

Front 57

Ketone body synthesis occurs in what organnelle in what organ?

Back 57

Liver only: mitochondrial matrix

Front 58

This molecule is the only water soluble lipid derived energy carrying product

Back 58

B-hydroxybutyrate

Cannot be utilized by the liver, must enter circulation

Front 59

B-hydroxybutryate is converted back into acetoacetate.

It is then catalyzed by a reaction using succinyl-CoA as a cofactor

Back 59

Products:

2 AcCoA's, which combine with OAA to form 2 citrates

Front 60

These pathways occur in what organelle?

1. Activate the polar head group (choline or ethanolamine) and condense with a DAG

2. Activate the glycerol backbone and condense with a polar head group

Back 60

Occur in the endoplasmic reticulum

Difference is what is activated to build phospholipid

Front 61

Lung surfactant.

Coats alveolar sacs
Reduces surface tension
10x less pressure for inflation
Absense = respiratory distress syndrome

Back 61

Lecithin

Occurs in infants who do not have enzyme to make phosphatidylcholine

Front 62

Pick one:

Between phosphatidylethanolamine or phosphatidylcholine, which one can be catalyzed to form phosphatidylserine?

Back 62

Phosphatidylethanolamine

Front 63

- Major player in signaling
- Binds to ER or SR
- Signals calcium to be dumped into cytoplasm

Back 63

Phosphatidylinositol

(remember, IP3 from physiology)

Front 64

Two phosphatidic acids linked by glycerol moiety

- Critical membrane lipid: 30-35% of inner mitochondrial membrane

Back 64

Cardiolipin

Front 65

An ester linkage rather than an ester at C1

Synthesized in peroxisomes (where some FA metabolism and plant FA digestion occurs)

Back 65

Plasmalogens (ether lipids)

Front 66

A plasmologen with choline in the R group will be found where?

Back 66

In the heart

Front 67

A plasmologen with ethanolamine in the R group will be found where?

Back 67

Myelin

Front 68

- Aggregates platlets at 10^-11 M
- Potent anti-hypertensive
- Involved in allergic response

Back 68

Platelet Activating Factor

Front 69

This fat is derived from serine and two fatty acids, one of which is bound to a nitrogen

Back 69

Ceramide

Serine with a fatty acid linked to Nitrogen - only place you'll see it

Front 70

This sphingolipid is critical in neural tissue

Back 70

sphingomyelin

Front 71

Could be converted into a glucocerebroside

Back 71

Galactocerebroside

Front 72

- Addition of NANA to a glucocerebroside forms a _________

Back 72

Ganglioside

Front 73

- Sugar acid
- Negatively charged
- CMP sugar

Back 73

NANA (N-acetylneuraminic acid)

Front 74

1. UDP-Glc
2. UDP-Gal
3. UDP-GalNac
4. CMP-NANA
5. UDP-Gal

Back 74

Ordered sequential steps in formation of ganglioside GM1

Front 75

The lysomsome uses specific glycosyl hydrolases for sqequential removal of each sugar residue

Back 75

Degradation of gangliosides

Lack of hydrolase to cleave the bond between Gal-GalNAC = GM2 accumulates.

This is called Tay-Sach's disease

Front 76

Carbohydrate moieties of glycolipids on the surface of cells.

When present on the surface of cells, the ABO carbs are linked to ____________ and are therefore the glycosphingolipid class

Back 76

sphingolipid

ABO markers confer antigenic determinants on the cell, especially RBCs

Front 77

H-antigen
A-antigen
B-antigen

Back 77

H antigen gives O blood type

Front 78

Molecule when carbon six is a methyl group instead of a carboxyl group

Back 78

Fucose

Front 79

The only sphingolipid that has a phosphate group

Back 79

Sphingomyelin

Front 80

Acety-CoA -> Mevalonate

Back 80

First step of cholesterol synthesis

Front 81

Mevalonate -> Isopentynyl-PP

Back 81

Second step of cholesterol synthesis

Front 82

Isopentynyl PP -> Geranyl-PP -> Farnesyl-PP -> Squalene

Back 82

Third step of cholesterol synthesis

Front 83

Cyclization of squalene and formation of cholesterol

Back 83

Fourth step of cholesterol synthesis

Front 84

- Incorporation into lipoproteins
- Bile salts


- Steroid hormones

Back 84

Liver

Steroid hormones produced in adrenal and gonads

Front 85

- Liver
- Intestine
- Adrenal cortex
- Gonads

Back 85

Major sites of cholesterogenesis

Front 86

All cell types can synthesize cholesterol, but they derive it from plasma lipproteins secreted by the _______ and ______.


If they do not provide an adequate supply, de novo synthesis of cholesterol is activated

Back 86

Liver and intestine

Front 87

Cholesterol feedback mechanism targets what enzyme?

Back 87

HMG-CoA reductase

Front 88

1. Cholesterol will block transcription of the HMG-CoA reductase gene (means there will be no HMG CoA reductase mRNA. No mRNA = no protein)

2. An AMP activated protein kinase phosphoyrlates and inactivates HMG CoA Reductase

3. HMG-CoA Reductase is the target of the statin family of drugs. These drugs function as competitive inhibitors of the enzyme

Back 88

Regulation of cholesterol synthesis.

Protein kinase A phosphorylates and inactivates HMG CoA reductase.

Rationale: Low ATP = do not want to make cholesterol

Front 89

These drugs reduce:

- Total cholesterol levels
- LDL
- apo B
- TAGs

Increase HDL

Back 89

Statins

Front 90

Getting rid of bile salts is important in lowering ones cholesterol. What substance helps?

Back 90

Fiber

Front 91

- Coronary artery disease
- Multiple sclerosis
- Bone Fractures
- Alzehimers disease
- Aortic valve disease
- Cancer

Back 91

Statins are used to treat these diseases

Front 92

___% of total cholesterol produces goes to bile salt production

Back 92

80%

Bile salts act as a detergent, has both hydrophobic and hydrophilic molecules

Front 93

1) Hdryxylate the steroid nucleus

2) Cleave the side chain to generate a bile acid

3) Conjugate the acid to a glycine or taurine

Back 93

Set of reactions that take place in the liver for bile salt production

Front 94

Primary bile salts

Gives cholesterol an acid function.

Removes three carbons from cholesterol (C27) to C24 Cholic acid or Chenocholic acid.

Pka of acid = 6.0.
Pka of intestine = 6.0

What's the problem?

Back 94

Problem: Only 50% of the compund is ionized.

Want all of the groups ionized.

Note: Cholic acid has three hydroxyls while Chenocholic acid only has two.

Front 95

Rate limiting step of primary bile salt production:

Cholesterol reduction to 7-a-hydroxycholesterol

Back 95

7-a-hydroxylase requires:

- O2
- P450 cytochrome containing iron
- NADPH

Front 96

3a, 7a-hydroxycholesterol gives rise to what two products?

Back 96

1) Chenocholic acid or
2) 3,7,12 hydroxycholesterol ---> Cholic acid

Front 97

Secondary bile salt

Conjugation lowers the pKa.

Activate the carboxyl group of the side chain by making the CoA derivative.

Back 97

Once Acetyl-CoA has been added, can add glycine or taurine to complete conjugation.

Glycocholate = pka 4
Taurocholate = pka 2

Front 98

Built from dietary lipid in the epithelial cells of small intestine.

Dietary TAG delivery system

Back 98

Chylomicrons

Front 99

Remains after TAG removed from chylomicron

Back 99

Chylomicron remnant

Front 100

Synthesized and secreted by the liver. TAG rich

End product of fatty acid synthesis in liver

Back 100

VLDL

Front 101

Higher density particle after TAG removal in the periphery by lipoprotein lipase.

Back 101

IDL

Front 102

Further degradation of TAG of IDL geenrates a particle rich in cholesterol and cholester esters, and of a higher density.

Cholesterol delivery particle

Back 102

LDL

Front 103

Synthesized and secreted in an immature form by liver and gut.

Matures by interacting with chylomicrons and VLDL in circulation where it exchanges lipids and proteins

Back 103

HDL

Front 104

1. Transfers apolipoproteins to other lipoproteins (directs metabolism of chylomicrons and VLDL)

2. Picks up lipids from other lipproteins

3. Picks up cholesterol from cell membranes

4. Converts cholesterol to cholesterol esters (LCAT)

5. Transfers cholesterol esters to other LP's, which transport them to liver

Back 104

Mechanisms in which HDL works

Front 105

Receptor:

B48, C, E

Back 105

Chylomicron

Front 106

Receptor:

B48, E

Back 106

Chylomicron remnant

B48 + E are recognized by liver

Front 107

Receptor:

B100, C, E

Back 107

VLDL

Front 108

Receptor:

B100, E, (some C)

Back 108

IDL

E recognized by liver

Front 109

Receptor:

B100

Back 109

LDL

B100 recognized by liver and peripheral cells and tissues

Front 110

Receptor:

A, C, E

Back 110

HDL

Recognized by liver and steroidogenic tissues

Front 111

Same gene in both intestine and liver, but RNA editing stops transcription early.

Back 111

B-apoliprotein gene

Stops the transcription of Apo B in intestine

Front 112

Recognizes B100 and E

Binds with preferance for LDL, but will bind VLDL, IDL, and chylomicron remnants.

Expression is high in liver and adrenal. Expressed in most other tissues

Back 112

LDL receptor

Front 113

Recognizes apo E

Binds chylomicron remnants and VLDL

Expression is high in liver, brain and lung. Modest elsewhere

Back 113

LDL receptor related protein (LRP)

Front 114

Binds various types of molecules including LDL that has been subjected to oxidative damage.

Involved in foam cell formation and atherosclerosis

Back 114

Macrophage Scavenger Receptor

Front 115

Synthesized by adipose and muscle tissue.

Transported to the surface of the vascular endothelium where it binds to heparan sulfate proteoglycans.

Back 115

Lipoprotein lipase (LPL)

Responsible for the hydrolysis of TAGs present in chylomicrons, VLDL and IDL to free fatty acids and glycerol.

FFA's are taken into adipose tissue for resynthesis of TAG or to muscle for oxidation

Front 116

- Can be displaced by giving a bolus of heparin

- Useful in detecting deficiency in lipase

Back 116

Heparine Secretatogue

Front 117

Synthesized in the liver and associated with the liver plasma membranes.

Digests TAG associated with partially degraded lipoproteins

Back 117

Hepatic Triglyceride lipase (HTGL)

Front 118

Mediates the exchange of lipid components between lipoproteins.

Transfers cholesterol esters from HDL to VLDL, IDL or LDL in exchange for TAGs

Back 118

Cholesterol Ester Transfer Protein (CETP)

Front 119

Associated with HDL particle

Esterifies cholesterol remaining on the surface of HDL.

This changes the polarity of the compound and the cholesterol ester moves to the inside of the particle.

Changes the shape of HDL from a disc to a sphere

Back 119

Lecithin cholesterol acyl transferase (LCAT)

Phosphatidylcholine + cholesterol -> cholesterol ester + lyso-phosphatidylcholine

Front 120

Located in the lysosome

Responsible for hydrolysis of LDL derived cholesterol esters to free cholesterol and a fatty acid

Back 120

Lysosomal acid lipase

Front 121

Intracellular enzyme mediates the esterification of cholesterol for storage

Acey CoA + cholesterol -> cholesterol oleate (18:1)

Back 121

Acyl CoA Cholesterol Acyl Transferase (ACAT)

Another enzyme that makes cholesterol esters.

Front 122

Pancreatic lipase needs colipase.

TAGs are broken down into 2 FFA's and a B-monoacylglycerol in the intestine.

Back 122

Colipase protects lipase from bile salt inhibition

Front 123

Unique to epithelial cell: Beta-acylmonoglycerol pathway.

1. TAG is pcaked with Apo A/B48/phospholipid/cholesterol

2. Forms a chylomicron

3. Goes to lymph

Back 123

Chylomicrons are too big for blood supply.

Front 124

This apoprotein is critical.

Interacts with LDL to activate lipase on adipose and muscle cells

Back 124

Apo C2

Front 125

Name the molecule:

Liver recognizes apo E

Apo E gives receptor recognition

Binds to LRP (LDL Receptor Like Protein)

Back 125

Chylomicron remnant

Front 126

From epithelial cell

-> Thoracic duct

-> Systemic circulation

-> HDL donates apo C2 and E to chylomicron

-> LPL on capillary endothelium of adipose and muscle tissues activated by apo C2

-> Digest TAG's to 3 FFA and a glycerol. Fatty acids taken up by adipose (storage) or muscle (oxidation). Glycerol to tissue where it can be reutilized.

-> Remnant (particle without TAGs) gives up apo C2 back to HDL, then off to liver

-> Receptor on liver recognizes apo E on remnant

-> LIVER! Remnant internalized, components digested

Back 126

The steps of chylomicron degradation

Front 127

Short and medium chain (C4-C12) fatty acids generated by the action of pancreatic lipase are able to by-pass the re-synthesis of TAG in the epithelial cells of the small intestine.

These FA's can move directly into systemic circulation where they are picked up by albumin and delivered to tissues where they can be converted to fatty acyl CoA's and used to re-synthesize TAGs or be oxidized.

Back 127

Useful if an individual has a problem with chylomicron formation.

Front 128

Sucrose with fatty acids esterified where there is an OH

Cannot be hydrolized and is excreted unchanged

Back 128

Olestra

Front 129

- Made in the liver de novo

- Stuffed with TAG and delivers fatty acids to adipose and muscle

- Then turns into LDL

Back 129

VLDL molecule

Front 130

HDL picks up cholesterol from LDL

HDL donates C2 and E to LDL


This makes HDL more/less hydrophobic?

Back 130

Less

LCAT esterifies the cholesterol to a cholesterol ester to keep it hydrophobic

Front 131

These two apo's aid in receptor recognition

This one apo activates LPL

Back 131

Apo B100 and E

Apo C2

Front 132

Esterification is unimportant/critical for transport of cholesterol in the body?

Back 132

critical

Front 133

- Cell overloaded with cholesterol

- Only cell that doesn't downregulate is the liver

- Regulation occurs at the level of the gene

Back 133

Regulation of cholesterol - turn off synthesis of LDL receptor and HMG-CoA reductase

Front 134

- Excess cholesterol is stored as cholesterol oleat (ACAT)

This makes another cholesterol ester inside of the cell and stores it

Back 134

ACAT

Front 135

Lysosomal acid lipase hydrolyzes the cholesterol ester.

This regenerates the B100 receptor and allows cholesterol to exit the lysosome for the cytoplasm

Back 135

Action of Lysosomal acid lipase

Front 136

1. Secreted into circulation by liver and gut. Contains (apo A, C and E)

2. Small and discoid in nature. Nearly devoid of cholesterol esters and TAGs

3. Donates apos C2 and E to VLDL and chylomicrons

4. Picks up cholesterol from other lipoproteins and the membranes of extrahepatic cells.

5. Cholesterol converted to cholester esters by LCAT, which is stilated by apo A1

6. As particl fills with cholester esters, it becomes spherical. Known as HDL3

Back 136

The Role of HDL.

Notes: A1 stimulates LCAT

HDL3 = spherical shape (aka, not the usual shape which is discoid)

Front 137

CETP can mediate the transfer of cholesterol esters from HDL3 to VLDL

OR HDL3 can bind to the surface of cells and transfer its cholesterol esters to the cell, the dissociate and re-enter circulation

AND

Mediate the transfer of TAGs from VLDL to HDL3.

Back 137

Reverse Cholesterol Transport

Results in the movement of cholesterol from areas of excess to areas of need.

CETP is a free enzyme.

HDL2 = smaller particle

Front 138

Apos C2 and E donated back to HDL

HTGL removes TAG at the liver

HDL particles become smaller and are designated HDL2

Back 138

Mechanism of CETP action

Front 139

Plaques form in walls of major arteries - impedes blood flow.

Composed of smooth muscle cells, connective tissues, lipids and debris

Back 139

Atherosclerosis

Front 140

1. Damage to endothelial cells of the arterial wall.

2. Macrophages arrive at site to deal with the damage.

3. Macrophages have "scavenger receptor" that will bind and internalize "oxidized LDL"

4. Macrophages become engorged with LDL derived lipid material. Turn into Foam Cells, the earliest physical sign of atherosclerosis.

6. Macrophages in the lesion release growth factors and stimulate growth of endothelial cells.

7. Cells in the lesion secrete collagen and other molecules that leads to the build up of a fibrous cap. Cells trapped and die (this is a plaque)

8. Rupture and hemorrhage of encapsulated plaque may cause the acute formation of a clot, which further occludes the vessel -> myocardial infarction

Back 140

Mechanism of Atherosclerosis

Front 141

Synthetic HDL - based on gold nanoparticle.

Binds cholesterol and can potential eat away at cholesterol containing plaques

Back 141

The future of treatment for atherosclerosis