LIPIDS AND LIPO Flashcards
petroleum industry
Lipoproteins
redistributing dietary and hepatic-synthesized
triglycerides to peripheral cells mostly during fasting for energy needs or
storage as fat.
The very-low-density lipoproteins (VLDLs)
rich in cholesterol, which
start out as VLDLs, are like nearly empty tankers that just deliver cholesterol
to peripheral cells and return to the liver after their main cargo, triglycerides,
have been off loaded.
low-density lipoproteins (LDLs)
are the cleanup
crew, gathering up excess cholesterol for transport back to the liver.
Cholesterol is used by the body for such useful functions as facilitating
triglyceride transport by lipoproteins and maintaining the normal structure
and integrity of cell membranes, and as a precursor for steroid hormone
synthesis, but when in excess, it can lead to cardiovascular disease.
high-density lipoproteins (HDLs)
-Commonly referred to as fats.
-composed of mostly carbon-hydrogen ( C-H )
bonds, they are a rich source of energy and an
efficient way for the body to store excess calories.
-Insoluble in blood and water, but soluble in
organic solvents
-Transported by lipoproteins , namely
triglycerides, phospholipids, cholesterol, and fat
soluble vitamins (ADEK)
LIPIDS
Linear chains of C-H bonds that terminate with a carboxyl group
(- COOH).
As to length can be classified as short-chain (4 to 6 carbon atoms),
medium-chain (8 to 12 carbon atoms), long-chain (12 to 18 carbon
atoms), or very-long-chain (>20 carbon atoms) fatty acids.
As to the number of C=C bonds, they can be saturated or unsaturated
Mostly found as constituents of phospholipids or triglycerides
Mainly derived from hydrolysis of triglycerides in adipose tissues
Small amount is present in plasma, most is bound to albumin.
Important source of energy
Provide the substance for conversion of glucose
Reference value: 9-15 mg/dl
FATTY ACIDS
Triacyglycerol (neutral fat)
3 molecule of fatty acid and one molecule of glycerol by ester bond
Hydrophobic and water soluble
Main storage of lipid in man ( adipose tissue) - 95% of stored fat and the predominant form
of glyceryl ester found in plasma
Breakdown of TAG are metabolized, their fatty acids are release to the cells and converted
into energy
Breakdown of TAG are facilitated by:
> lipoprotein
> lipase
> epinephrine
> cortisol
TRIGLYCERIDES
Fasting requirement for triglycerides
12-14 hours
Reference value for lipids
9-15 mg/dl
Reference value for triglycerides in Normal state
<150 mg/dl
Reference value for triglycerides in Borderline High
150-199 mg/dl
Reference value for triglycerides in High TAG
200-499 mg/dl
Reference value for triglycerides in Very High TAG
200-499 mg/dl
Chemical Methods
I. Colorimetric Method (Van Handel and Zilversmith)
II. Flourometric Method (Hantzsch Condensation)
Enzymatic Methods
major interference; normally present in plasma
concentration below 0.163 mmol/L, equivalent to 14 mg/dL TAG
concentration
Glycerol
Hydrolysis of TAG to free fatty acids and glycerol,
followed by the phosphorylation of glycerol to glycerophosphate
Glycerol Kinase Method
Involves alkaline
hydrolysis (saponification) using alcoholic KOH, solvent extraction with chloroform
and the extract is treated with silicic acid (chromatography) to isolate TAG and a
color reaction with chromotopic acid, giving rise to a pink end color
CDC reference method (Modified Van Handel and Zilversmith)
Increased Triglycerides BECAUSE OF
Hyperlipoproteinemia Types I,
IIb, III, IV, and V
Nephrotic syndrome
Alcoholism
Hypothyroidism
Pacreatitis
Decrease Triglycerides BECAUSE OF
Malabsorption
Hyperthyroidism
Malnutrition
Brain Infarction
Most abundant lipids derived from phosphatidic acid
* Originates in the liver and intestine
* Produced from the conjugation of two fatty acids and phosphorylated
glycerol
* Amphipathic lipid, contains polar hydrophilic head groups and non polar
hydrophobic fatty acid side chains
* Similar structure to triglycerides, except they contain two fatty acids
* Alter fluid surface tension
* Participate in cellular metabolism and blood coagulation
PHOSPHOLIPIDS
Reference value of PHOSPHOLIPIDS
150-380 mg/dL
what are the forms of Phospholipids
Lecithin/Phosphatidyl choline — 70%
* Spingomyelin — 20%
* Cephalin — 10%
- Phosphatidyl ethanolamine
- Phosphatidyl serine
- Lysolecithin + Inositol Phosphatide
Only phospholipid in membranes that is not derived from glycerol but from an amino
alcohol called sphingosine
* Essential component of cell membrane
* Accumulates in liver and spleen of patients suffering Niemann-Pick disease
* Serve as reference material during 3rd trimester of pregnancy because its
concentration is constant as oppose to lecithin
SPHINGOMYELIN
- Unsaturated steroid alcohol containing 4 rings, and it has a single C-H
side chain tail similar to fatty acid - Amphipathic hydroxyl group in the A-ring is the hydrophilic part of
cholesterol - Found on the surface of lipid layers; synthesized in the liver
- Almost exclusively synthesized by animals; not catabolized by most
cells-does not serve as source of fuel - Transport and excretion is promoted by estro
CHOLESTEROL/ 3-HYDROXYL-5,6-CHOLESTENE
CHOLESTEROL/ 3-HYDROXYL-5,6-CHOLESTENE (FUNCTION)
- Progestins
- Glucocorticoids
- Mineralocorticoids
- Androgen
- Estrogen
WHAT ARE THE Forms of Cholesterol
Cholesterol Ester 70%
Free cholesterol 30%
Chemical Methods for CHOLESTEROL/ 3-HYDROXYL-5,6-CHOLESTENE
- Liebermann Burchardt Reaction End product: Cholestadienyl Monosulfonic Acid
(Green) - Salkowski Reaction End product: Cholestadienyl Disulfonic Acid (Red)
General Methods for CHOLESTEROL/ 3-HYDROXYL-5,6-CHOLESTENE
- One-step Method = colorimetry
- Two-step Method = extraction + colorimetry
- Three-step Method = saponification + extraction + colorimetry
- Four-step Method = saponification + extraction + colorimetry + precipitation
Increased Cholesterol
Hyperlipoproteinemia
types II, III, V
Biliary cirrhosis
Nephrotic syndrome
DM
Alcoholism
Primary hypothyroidism
Decreased Cholesterol
Severe hepatocellular
Hyperthyroidism
Malnutrition
Malabsorption syndrome
General Lipoprotein Structure
Apolipoprotein
Cholestereyl-ester
Triglycerides
Cholesterol
Phospholipids
Apolipoproteins are located on the surface of lipoprotein particles.
They help maintain the structural integrity of lipoproteins.
They serve as ligands for cell receptors.
They act as activators and inhibitors of enzymes that modify lipoprotein particles.
Apolipoproteins contain an amphipathic α helix structural motif.
This motif allows the proteins to bind to lipids.
Amphipathic helices have hydrophobic and hydrophilic regions.
Keep the lipids in solution during circulation through the blood stream
Aid in solubilization of the lipids and also in their transfer from the gastrointestinal tract to
the liver
Interact with specific receptors and direct the lipids to the correct target organs and
tissues in the body
Apolipoprotein
major lipoproteins
Chylomicrons (CM)
Very Low Density Liproprotein/Pre-Beta Lipoprotein (VLDL)
High Density Lipoprotein/Alpha Lipoprotein (HDL)
Low Density Lipoprotein/ Beta Lipoprotein (LDL)
Largest and less dense of lipoprotein particles
* Produced in the intestine from dietary fat; completely cleared within 6-9 hours post prandial
* Transport exogenous/dietary TAG to liver, muscle and fat depot
* Major composition: 90% TAG + 1-2% protein
* Apolipoprotein: Apo B-48, Apo A-1, Apo C and Apo E
* Density: <0.95 kg/L
Chylomicrons (CM)
Secreted in the liver
* Transport endogenous TAG to liver, muscle, fat depot and peripheral tissues
* Major composition: 65% TAG + 6-10% protein + 16% CE
* Apolipoprotein: Apo B-100, Apo C and Apo E
* Density: 0.95-1.006 kg/L
Very Low Density Liproprotein/Pre-Beta Lipoprotein (VLDL)
- Smallest lipoprotein (5-12nm) but the most dense
- Produced in the liver and intestine
*Transports excess cholesterol from the tissues and return it to the liver
(reverse cholesterol transport) - HDL maintains the equilibrium of cholesterol in peripheral
cells by the reverse cholesterol transport pathway. - CDC reference method: ultracentrifugation, precipitation with heparin-MnCl, and AbellKendall Assay
- Major composition: 30% phospholipid + 45-50% protein + 20% CE
- Apolipoproteins: Apo A-I, Apo A-ll and Apo C
- Reference value: 40 mg/dl * Density: 1.063-1.21 kg/L
High Density Lipoprotein/Alpha Lipoprotein (HDL)
Synthesized in liver
* Major end product from the catabolism of VLDL
*Transport cholesterol to the peripheral tissues-it carries most of the circulating
cholesterol and transports cholesterol to hepatic and extrahepatic tissues, where it is
taken up by the LDL-receptor-mediated endocytosis
* Most cholesterol rich of lipoproteins and most atherogenic
* Major composition: 50% CE +18% protein and phospholipid
* Apolipoproteins: Apo B-100 and Apo E
* Research method: Beta quantification
* Reference value: <100 mg/dL
* Density: 1.019-1.063 kg/
Low Density Lipoprotein/ Beta Lipoprotein (LDL)
- An aliquot of plasma (2 mL) is placed into a 10 x 75-mm test tube and allowed to stand in the
refrigerator at 4° C undisturbed overnight. - Chylomicrons accumulate as a floating “cream” layer and can be detected visually.
- A plasma sample that remains turbid after standing overnight contains excessive amounts of
VLDL
STANDING PLASMA TEST
MINOR lipoproteins
Intermediate Density Lipoprotein (IDL)
Lipoprotein (a) / Lp(a)
- Product of VLDL catabolism- “VLDL remnant”
- Converted to LDL- “subclass of LDL”
- Defective clearance of IDL in type 3 hyperlipoproteinemia is probably due to deficiency
of Apo E-III - Major lipoprotein: Apo B-100
- Density: 1.006-1.019 kg/L
Intermediate Density Lipoprotein (IDL)
Intermediate Density Lipoprotein (IDL)
Lipoprotein (a) / Lp(a)
ABNORMAL LIPOPROTEINS
Lipoprotein X
B-VLDL (floating ẞ lipoprotein)
The four major pathways involved in lipoprotein metabolism:
- Lipid Absorption Pathway
- Exogenous Pathway
- Endogenous Pathway
- Reverse Cholesterol Transport Pathway
- Found in obstructive jaundice and LCAT deficiency
- Specific and sensitive indicator of cholestasis
- Lipid content is mostly phospholipid and free cholesterol
- Contains Apo A and Albumin
Lipoprotein X
*“abnormally migrating B-VLDL”
* Found in type 3 hyperlipoproteinemia or dysbetalipoproteinemia
* “VLDL rich in cholesterol”
* There is an accumulation of IDL because of failure to fully convert VLDL to LDL
* Density: <1.006 kg/L
B-VLDL (floating ẞ lipoprotein)
DISORDERS ASSOCIATED WITH LIPIDS AND
LIPOPROTEINS
Arteriosclerosis
Hyperlipoproteinemia
Hypercholesterolemia
PCSK9
HYPERTRIGLYCERIDEMIA
Combined Hyperlipidemia
Lp(a) Elevation
Non-HDL Cholesterol
Hypoalphalipoproteinemia
Familial Hypercholesterolemia (Type 2a)
Hypobetalipoproteinemia
Abetalipoproteinemia (Bassen-Kornzweig Syndrome)
Niemann-Pick disease (lipid storage disease)
Familial Dysbetalipoproteinemia (Type 3 Hyperlipoproteinemia)
Tangier’s Disease
Lipoprotein Lipase (LPL) Deficiency
Lecithin Cholesterol Acyl Transferase (LCAT) deficiency
Tay-Sachs disease
Chylomicron Retention Disease (Andersen’s Disease)
Sitosterolemia
FREDRICKSON CLASSIFICATION
Type 1- Hyperchylomicronemia/Familial LPL Deficiency
Type 2- Hyperlipoproteinemia
Type 3 Dysbetalipoproteinemia
Type 4 Hyperlipoproteinemia/ Hypertriglyceridemia
Type 5 Hyperlipoproteinemia
