Lipid Metabolism And Disorder

Front 1

Describe the lipoprotein (4)

Back 1

Water miscible assembly:
- nonpolar lipids (TG, CE)
- amphipathic lipids (phospholipid, cholesterol)
- proteins (apoprotein)

- density↓, size ↑, when fat to protein ratio ↑
[most lipid, least protein in chylomicrons]
[least lipid, most protein in HDL]
*protein contributes to enzyme activation+receptor specificity too*

Front 2

- function of lipoprotein (3+1)

Back 2

1. Transports lipid in blood to tissue (oxidation) and adipose (storage)
- exogenous pathway: from intestine (chylomicrons)
- endogenous: from liver (VLDL)
- Free FA frm adipose mobilized: bind to serum albumin

2. also to replenish RBC membrane lipid

Front 3

Classification of lipoproteins (4)
- important apolipoproteins (3)
- where is each lipoprotein from? (3)
- function of each lipop (4)

Back 3

1. Chylomicrons (apo B-48)
- transport dietary TG & chol. from intestines to tissue
- exogenous pathway
- from epithelial cells of villi in duodenum

2. VLDL (apo B-100)
- transport endogenous TG & chol from liver to tissue
(endogenous)
- from LIVER

3. LDL
- transport chol to liver & tissue
- final stage in VLDL catabolism

4. HDL (apo A-1)
- receive chol. from tissue to [lipoprotein & liver]
- repository of apo-II & apoE for chylo maturation
- VLDL origins from hepatocyte/enterocyte
- HDL1, HDL2, HDL3 ↑density (↓lipid content)

Front 4

what is the relationship between HDL and CHD

Back 4

Protects against CHD
- removes chol. from tissue
- compete w. LDL for uptake by tissue
- receive surface component from chylomicron metabolism ↑HDL2

Front 5

apoprotein
- structural component of lipoprotein (4)
- enzyme cofactors/inhibitors (2)
- ligands for receptors (2)

Back 5

Structural component of lipoprotein
- apo B48: chylomicrons
- apo B-100: VLDL
- apo C-I, C-II, C-III (freely transferable between diff. lipoproteins)
- apo E: HDL, VLDL, chylomicrons, chylo remnants

Enzyme cofactor/inhibitor
- apo C-II: stimulate LPL
- apo A-II, C-III: inhibit LDL

Ligands for receptors
- apo B-100, apo E: LDL receptors

Front 6

Key enzymes of plasma lipid transport (4)

Back 6

lipoprotein lipase,
hepatic lipase
lecithin: cholesterol acyltransferase
cholesterylester transfer protein

Front 7

Lipoprotein lipase
- substrate? (3)
- source [3]
- cofactor [1]
- functions

Back 7

- substrate: TG, phospholipids of chymo, large VLDL
- source: adipose, striated ms, BV endothelium
- requires apo C-II as cofactor
- functions: hydrolyze TG in chylomicrons/VLDL to glycerol & FA

Front 8

Hepatic lipase/Hepatic triacylglycerol lipase (HTGL)-
- substrate? (4)
- source [1]
- functions [2]

Back 8

Final catabolism of chylomicron remnant
- substrate: TG, phospholipid of VLDL, IDL, HDL
- source: liver
- functions: convert IDL→LDL, HDL2→HDL3

Front 9

Lecithin : cholesterol acyltransferase
- substrate? (1]
- source [1]
- functions [1]
- what is it found in?

Back 9

- chol & phosphatidylcholine of species of HDL
- Liver
- convert cholesterol → CE core of lipoprotein
- present mostly in HDL, lesser in LDL

Front 10

Cholesterylester transfer protein
- function [2]

Back 10

- facilitate exchange of CE & TG between HDL & non-HDL lipoprotein
- TG: VLDL/LDL → HDL, CE: HDL → VLDL/LDL

→ ← ↑ ↓

Front 11

classes of lipid metabolism disorder (3)

Back 11

1. Transport disease
- genetic defects→faulty apoproteins/receptors
- abnormal high (or low) lipoprotein levels: risk of DM and IHD

2. Lipid storage disease
- inability to break down lipid→accumulation in tissue

3. Disease of complex multifactorial etiology
- changes in lipid metabolism;
direct/common indirect role in DM & obesity

Front 12

causes of lipid metabolism disorder (2)

Back 12

1. primary/familial
- inherited, inborn errors of metabolism
- gene defect for specific/receptor
- failure of regulatory gene

2. secondary/acquired
- result of another disease [reversible]
- nutrition/diet can control/modify/reverse dx
e.g. DM, hypothyroidism, renal failure, alcohol, diuretic use, BB, estrogens

Front 13

Types (2) and Causes (5) of hyperlipidemia

Back 13

Types:
- 1° hyperlipoproteinemia (hypercholesterolemia, hypertriglyceridemia)
- 2° hypolipoproteinemia (hypocholsterolemia, hypotriglyceridemia)

Causes
- Absence of specific enzyme in lipid metabolism
- Absence of specific apolipoprotien
- Absence/reduction/impairment of function of specific cell surface receptors
- OVERPRODUCTION of specific apolipoprotein
- OVERPRODUCTION of lipids in liver

Front 14

Fredrickson classification of primary hyperlipidemia?

Back 14

I: exogenous hyperlipidemia, ↑chylomicrons
IIa: hypercholesterolemia, ↑LDL
IIb: combined hyperlipidemia, ↑LDL+VLDL
III: remnant hyperlipidemia, ↑remnant (beta-VLDL)
IV: endogenous hyperlipidemia, ↑VLDL
V: mixed hyperlipidemia, ↑chylomicrons+VLDL

Front 15

familial hypercholesterolemia (FH)
- genetics (2)
- clinical signs (2)

Back 15

- Type IIa, ↑LDL (most common)

- autosomol dominant
- frequency of heterozygots: 1 in 500. plasma chol 2X

- xanthomas, atherosclerosis, CHD, angina
(occlude brain a. (stroke), peripheral artery occlusion disease, gangrene)
- 5% MI patients <60 y/o
- heterozygotes: (75%♂, 50%MI, 45%♀, 15%MI)
- homozygotes: MI <20 y/o (die at 30 if untreated)

Front 16

Hypertriglyceridemia
- biochemical levels
- types (2)
- treatment (3)

Back 16

- TG > 250 mg/dl

1. Familial hypertriglyceridemia (type IV)
- overproduction of VLDL-TG
- defective VLDL lipolysis (esp. obese, diabetics)

2. Familial combined hyperlipidemia (type IIb)
- overproduction of apoB so ↑VLDL (premature CHD)

Tx:
- weight reduction (diet control, exercise)
- nicotinic acid
- gemfibrozil

Front 17

Abetalipoproteinemia/Bassen-Kornzweig syndrome
- defect in?
- symptoms (5)
- tx (1)

Back 17

- defect in apo B (48, 100) production: so very low level of total lipid, chol, TG, phospholipid

Symptoms
- psychomotor retardation
- multiple nutrional deficiencies (A,D,E,K) although most effects due to vit E
- multiple neuromuscular consequences
- abnormal RBC acanthocyte (spiked cell membrane)
- retinitis pigmentosa (no vit A). loss of vision

Tx: massive dose of vit E

Front 18

hyperchylomicronemia (Type I)
- biochemical findings (2)
- defects (4)
- clinical symptoms (4)
- therapy (1)

Back 18

- proportionate ↑in cholesterol & TG
- ↑plasma chylomicrons

- LPL deficiency in capillary endothelium
- absence of HDL carrying apoC-II & apoE
- abnormal apoproteins (C-II)
- CETP deficiency

- tissue deposition of lipids
- recent memory loss
- abdominal pain
- lipemia retinalis (severe)

- ↓dietary fat intake