LIPIDS & LIPOPROTEINS Flashcards
Primary source of fule, provide stability to cell membrane and allow for transmembrane transport
Lipids
Lipids are insoluble in blood and water, but soluble in ___
organic solvents like chloroform and ether
Most abundant lipids derived from phosphatidic acid
Phospholipid (Conjugated Lipid)
Phospholipid is produced from the conjugation of
two fatty acids & phosphorylated glycerol
Reference Value of Phospholipid
150-380 mg/dL
Serum
Only phospholipid in membranes that is not derived from glycerol but from an amino alcohol called sphingosine
Sphingomyelin
Sphingomyelinase accumulates in the liver and spleen of patients suffering from what disease
Niemann-Pick disease
Lipid storage disorder
Mature lung function correlates strongly with a Lecithin/Sphingomyelinase ratio of
less than or equal to 2
Unsaturated steroid alcohol containing four rings, has a single C-H side chain tail similar to fatty acid
Cholesterol
Where is Cholesterol synthesized
Liver
Reference value of Cholesterol
< 200 mg/dL
Borderline Cholesterol
200-239 mg/dL
High Cholesterol
> or = 240 mg/dL
Cholesterol is the precursor of five major classes of steroids
- Progestins
- Glucocorticoids
- Mineralocorticoids
- Androgens
- Estrogens
Cholesterol bound to fatty acid
Found in plasma and serum
Cholesterol Ester
70% of cholesterol
Cholesterol bound to fatty acid
Found in plasma and serum
Cholesterol Ester
70% of cholesterol
Cholesterol ester undergoes esterification by what enzyme
LCAT
Lecithin-Cholesterol Acyltransferase
LCAT promotes the transfer of fatty acid from lecithin & cholesterol and forms
Lysolecithin
Cholesterol Ester
Activator of LCAT:
Apo-1
A polar nonesterified alcohol
Found in Plasma, serum and RBCs
Free Cholesterol
30% of Cholesterol
A polar nonesterified alcohol
Found in Plasma, serum and RBCs
Free Cholesterol
30% of Cholesterol
Patient preparation for Cholesterol testing
Patient should be in their usual diet
Neither gaining nor losing weight
End product:
Choestadienyl Monosulfonic Acid
Green color
Chemical Method
Liebermann Burchardt Reaction
End product:
Cholestadienyl Disulfonic Acid
Red color
Chemical Method
Salkowski Reaction
Color Developer Mixture
Liebermann Burchardt Reagent
- Glacial Acetic Acid
- Acetic Anhydride
- Concentrated H2SO4
One-Step
Colorimetry
Example of One-step method
Pearson, Stern and Mac Gavack
Two-Step Method
Extraction + Colorimetry
Example of Two-Step
Bloors
Three-Step Method
Saponification + Extraction + Colorimetry
Example of Three-step method
Abell-Kendal
Four-Step Method
Saponification + Extraction + Colorimetry + Precipitation
Example of Four-Step method
Schoenheimer, Sperry, Parekh & Jung
Most common method of quantifying cholesterol oxidase reaction is to measure amount of ___ produced
Hydrogen Peroxide
Enzymes used in Cholesterol Oxidase Reaction
Cholesterol Esterase
Cholesterol Oxidase
Peroxidase
CDC Reference Method for Cholesterol
Abell, Levy and Brodie Method
Uses hexane extraction after hydrolysis with alcoholic KOH followed by reaction with Liebermann-Burchardt color reagent
Abell, Levy and Brodie Method
- Hyperlipoproteinemia types II, III, V
- Biliary cirrhosis
- Nephrotic Syndrome
- Poorly controlled diabetes mellitus
- Alcoholism
- Primary hypothyroidism
Increased Cholesterol
- Severe hepatocellular disease
- Malnutrition
- Severe burns
- Hyperthyroidism
- Malabsorption syndrome
Decreased Cholesterol
Contains 3 molecules of fatty acid and one molecule of glycerol by ester bonds
Triglyceride
Main storage of lipid in man & constitutes 95% of stored fat and the predominant form of glyceryl ester found in plasma
Triglyceride or
Triacylglyceride
Breakdown of TAG is facilitated by what
Lipoprotein lipase (LPL)
Epinephrine
Cortisol
Fasting requirement for TAG
10-12 hours
Reference Value
1. Normal
2. Borderline high
3. High TAG
4. Very High TAG
- < 150 mg/dL
- 150-199 mg/dL
- 200-249 mg/dL
- > 500 mg/dL
Most important lipids in the management of coronary artery disease (CAD)
TAG
Cholesterol
Strategy for determining TAG concentration is to hydrolyze all fatty acid esters to produce what?
Glycerol
Colorimetric Method
Uses Chromotropic Acid and produces Blue color compound
Van Handel & Zilversmith
Fluorometric Method
Uses Diacetyl Acetone & Ammonia to produce Diacetyl Lutidine compound
Hantzsch Condensation
Involves hydrolysis of triglycerides to free fatty acids and glycerol, followed by the phosphorylation of glycerol to glycerophosphate
Glycerol Kinase Method
Uses Lipase, Glycerol Kinase, Pyruvate Kinase and LDH
What is the endpoint
Lactate
Glycerol kinase reaction a
Uses Lipase, Glycerol Kinase, Pyruvate Kinase and LDH
What is the endpoint
Lactate
Glycerol kinase reaction a
Uses Lipase, Glycerol kinase, Glycerol PO4 dehydrogenase, and Diaphorase
What is the end point
Formasan
glycerol kinase reaction b
CDC Reference Method for TAG
Modified Van Handel & Zilversmith
Involves alkaline hydrolysis using alcoholic KOH, solvent extraction with chloroform and the extract is treated with silicic acid to isolate TAG
End color: PINK
Modified Van Handel & Zilversmith
Linear chains of Carbon-Hydrogen bonds that terminate with a carboxyl group
Mostly found as constituents of phospholipids or triglycerides
Fatty Acids
Most of Fatty acids are bound to ___
Albumin
Reference Value of Fatty Acid
9-15 mg/dL
Fatty acids without double bonds:
Saturated fatty acids
Fatty acids with double bonds
Unsaturated Fatty Acids
Enzyme that hydrolyzes TAG & cholesterol esters in lipoprotein
Releases fatty acids and glycerol
Present on the surface of capillary endothelial cells in adipose tissues, cardiac and skeletal muscles
Lipoprotein Lipase
LPL
Enzyme that hydrolyzes TAG & cholesterol esters in lipoprotein
Releases fatty acids and glycerol
Present on the surface of capillary endothelial cells in adipose tissues, cardiac and skeletal muscles
Lipoprotein Lipase
LPL
Hydrolyzes TAG & Phospholipids from HDL
Hydrolyzes lipids on VLDL & IDL
Hepatic Lipase
Catalyzes esterification of cholesterol from HDL
Enables HDL to accumulate cholesterol as cholesterol esters
Lecithin Cholesterol Acyl Transferase
LCAT
Hydrolyzes phospholipids and TAG in HDL
Endothelial lipase
Used for effluz of cholesterol from peripheral cells into HDL
ATP-binding cassette protein A1
ABCA1
Used for effluz of cholesterol from peripheral cells into HDL
ATP-binding cassette protein A1
ABCA1
Large macromolecular complexes of lipids with specialized proteins known as apolipoproteins
Lipoproteins
Main purpose of Lipoproteins
Transport TAG & Cholesterol to sites of energy storage and utilization
Helps keep the lipids in solution during circulation through the bloodstream
Aids in the solubilization of lipids and their transfer from GI tract to LIVER
Apolipoprotein
Lasrgest and Least dense of the lipoprotein particles
Transports EXOGENOUS or dietary fat
Chylomicrons
Secreted in the liver
Transports ENDOGENOUS TAG from liver to muscle, fat deposits and peripheral tissues
Very Low Density Lipoprotein (VLDL)
Pre-Beta
Smalles lipoproteins but the most dense
Produced in liver and intestine
Transports excess cholesterol from tissues and return it to the liver
High Density Lipoprotein
Alpha Lipoprotein
CDC Reference Method for HDL
- Ultracentrifugation
- Precipitation with Heparin-MnCl2
- Abell-Kendall Assay (3-step method)
Reference Value of HDL
40 mg/dL
Major endproduct from catabolism of VLDL
Transports cholesterol to the peripheral tissues, carries most of the circulating cholesterol and transports it to hepatic and extrahepatic tissues
Low Density Lipoprotein
Beta Lipoprotein
Most Cholesterol-rich of the lipoproteins and
Most atherogenic
Primary marker for CHD risk
LDL
Reference Value of LDL
1. Optimal
2. Near Optimal
3. Borderline
4. High
5. Very high
- < 100 mg/dL
- 100-129 mg/dL
- 130-159 mg/dL
- 160-189 mg/dL
- > =190 mg/dL
Product of VLDL catabolism/ VLDL remnant
Converted to LDL
Migrates either in the pre B or B region
Intermediate Density Lipoprotein (IDL)
Similar to LDL
Also known as Sinking pre-B lipoprotein
Lipoprotein (a)
Abnormal lipoprotein found in Obstructive Jaundice & LCAT deficiency
Specific and sensitive indicator of Cholestasis
Lipoprotein X
Also known as “Abnormally migrating B-VLDL”
Found in Type 3 Hyperlipoproteinemia
VLDL rick in cholesterol due to defective catabolism of VLDL
Also known as Floating B lipoprotein
Beta-VLDL
Fasting Preparation:
10-12 hours
Reference method for quantification of lipoproteins
Based on the protein and TAG contents of lipoproteins
Ultracentrifugation
Expressed in Svedberg (s) units
Reference method for quantification of lipoproteins
Based on the protein and TAG contents of lipoproteins
Ultracentrifugation
Expressed in Svedberg (s) units
Electrophoretic pattern
HDL, VLDL, LDL, Chylomicrons
Preferred Supporting Medium
Agarose Gel
Lipid-Staining Dyes:
Oil Red O
Fat Red 7B
Sudan Black B
If this is present, it remains at the origin
Chylomicrons
Uses polyanions and divalent cations such as Mg, Ca, Mn
Chemical Precipitation
Currently considered the most important value in assessing cardiac risk and directing therapy
LDL-C
Friedewald Method
VLDL mmol/L
Plasma TAG/2.175
VLDL mg/dL
Plasma TAG/5
De Long Method
VLDL mmol/L
Plasma TAG/2.825
De Long Method
VLDL mg/dL
Plasma TAG/6.5
Autosomal dominant caused by defective or deficient LDL receptor
Cannot bind or clear LDL
(+) Xanthelasma & Planar Xanthomas
Familial Hypercholesterolemia
Accumulation of plasma VLDL rich in cholesterol and chylomicron remnants
Associated with presence of apo E2/2 (rare form of Apo E)
Familial Dysbetalipoproteinemia
Type 3 Hyperlipoproteinemia
Defective apo B synthesis
VLDL, LDL, Chylomicrons are not found in plasma
Chole & TAG are both decreased
Defects in absorption of fat-soluble Vitamins (A, E, K)
Abetalipoproteinemia
Bassen-Kornzweig syndrome
Apo-B deficiency resulting from point mutations in apo-B
Decreased: LDL-C, & TC
Hypobetalipoproteinemia
Inherited disorder, accumulations of sphingomyelin in bone marrow, spleen & lymph nodes
Niemann-Pick disease
Lipid Storage disease
Complete absence of HDL due to a mutation in the ABCA1 gene on chrom 3
Orange or Yellow discoloration of the tonsils and pharynx
Tangier Disease
Presents in childhood with abdominal pain & pancreatitis
Inability to clear chylomicron particles, creating the classic “type 1” chylomicronemia syndrome
Lipoprotein Lipase deficiency
Due to mutation in the LCST gene
HDL-C:<10mg/dL
Lecithin Cholesterol Acyltransferase Deficiency
Deficiency of the enzyme Hexosaminidase A, results in the accumulation of sphingolipids in the brain
Tay-Sachs Disease
Only ApoB-48 is affected
Chylomicron Retention Disease
Anderson’s disease
Plant sterols are absorbed and accumulate in plasma and peripheral tissues
Due to mutation in ABCG8 or ABCG5 gene
Sitosterolemia
Type 1 Hyperchylomicronemia
Familial LPL Deficiency
Increased:
TAG
CM
Low Cardiac Risk
Eruptive Xanthoma
Type 2a
Familial Hypercholesterolemia
Increased
Cholesterol
LDL
Xanthelasma & Tendon xanthoma
High Cardiac risk
Tendon Xanthoma & Xanthelasma
Type 2b
Mixed Defect
Familial Combined Hyperlipidemia
Increased:
TAG
CHOL
LDL
VLDL
High Cardiac Risk
Type 3
Familial Dysbetalipoproteinemia
Increased:
TAG
CHOLE
VLDL
Eruptive & Palmar Xanthoma
Type 4
Familial Hypertriglycedemia
Increased:
TAG
VLDL
Low Cardiac Risk
Type 5 Hyperlipoproteinemia
LPL Deficiency
Increased:
TAG
CHOLE
VLDL
CM
Most common primary hyperlipidemia
Familial combined hyperlipidemia
Type 2b
