Definition
§
Lipid; is any of
various organic compounds that are insoluble in water. Lipids are usually
referred to as fats and oils. Fats are materials that are solid
at ambient temperature and oils are those liquid at ambient temperature, stored
in the adipose tissue of the body. They include fats, waxes, oils, hormones,
and certain components of membranes and function as energy-storage molecules
and chemical messengers.
§
Protein; is a naturally occurring, extremely complex substance that
consists of amino acid residues joined by peptide bonds. Proteins are present
in all living organisms and include many essential biological compounds such as
enzymes, hormones, and antibodies.
§
Amino Acid; are molecules that
combine to form proteins. Amino acids and proteins are the building blocks of
life. When proteins are digested or broken down, amino acids are left. The
human body uses amino acids to make proteins to help the body:
§
Lipoproteins;
are substances made of protein and fat that carry cholesterol through your
bloodstream. Is
a particle consisting of
spherical non-polar (water insoluble) cores of a lipid such as triglycerides or
cholesterol esters surrounded by monolayer phospholipids, cholesterol and a
protein. These lipid-protein complexes are used to transport lipids in the
blood.
§
Apolipoproteins; are proteins
that bind lipids (oil-soluble substances such as fat and cholesterol) to form
lipoproteins. They transport lipids (and fat soluble vitamins) in blood,
cerebrospinal fluid and lymph.
§
Lipid profile; is a blood test
that measures lipids—fats and fatty substances used as a source of energy by
your body. Lipids include cholesterol, triglycerides, high-density lipoprotein
(HDL), and low-density lipoprotein (LDL). This panel measures: Total
cholesterol level.
§
Cholesterol; is a waxy
substance found in your blood. Your body needs cholesterol to build healthy
cells, but high levels of cholesterol can increase your risk of heart disease. Is a key component of lipid metabolism and a
major contributing factor in atherosclerosis.
§
Fatty acid; is any straight chain organic acid compound classified
as either saturated fatty acids, those with no double bonds, monosaturated,
fatty acids those with one double bond, and polysaturated fatty acids, those
with multiple double bonds. An essential fatty acid is not synthesized by the
human body but is required for maintaining health for example, Linoleic,
Linolenic acid.
§
Triglyceride; is an organic compound consisting of three molecules
of fatty acids bound to
glycerol.
§
Glycerol; is an organic
compound made from sugar and alcohol.
§
Phospholipid; is the major form
of lipids in cell membranes OR is any lipid
that contains phosphorus including those with a glycerol backbone
(phosphoglycerides) and sphingosine or substances (sphingomylins) Phospholipids
are the major form of lipid in cell membranes.
§
Atherosclerosis; is the hardening and narrowing of arteries due to
accumulation of fats and fibrin and calcification.
§ Enzyme; a substance produced by a living organism
which acts as a catalyst to bring about a specific biochemical reaction.
§ Co-Factor; is a non-protein chemical compound or metallic ion that is required
for an enzyme's role as a catalyst
§ Absorbance; Absorbance (A), also known as optical density
(OD), is the quantity of light absorbed by a solution.
§ Apolipoprotein B100(apoB100); is a protein that plays a role in moving cholesterol around your body.
It is a form of low density lipoprotein (LDL).
L I P I D S
The
four main groups of lipids include:
o
Fatty acids
(saturated and unsaturated)
o
Glycerides
(glycerol-containing lipids)
o
Nonglyceride
lipids (sphingolipids, steroids, waxes)
o
Complex
lipids (lipoproteins, glycolipids)
Metabolism of lipids
Lipid
metabolism involves the synthesis of the structural and functional lipids (such
as phospholipids, glycolipids, sphingolipids, cholesterol, prostaglandins,
etc.) that are characteristic of individual tissues and the degradation of
lipids to satisfy the metabolic needs of the body (e.g., energy production).
Lipid metabolism is in a constant state of dynamic equilibrium. This means that
some lipids are constantly being oxidized to meet the body's metabolic needs,
whereas others are being synthesized and stored.
·
Cholesterol:
·
Triglyceride metabolism:
Triglycerides and cholesterol combine to form
chylomicrons. Chylomicrons enter the circulation and travel to peripheral
sites. In peripheral tissues, free fatty acids are released from the
chylomicrons to be used as energy, converted to triglyceride or stored in
adipose. Remnants are used in the formation of HDL.
·
Concentration
of plasma TG is a balance between rate of entry into the body from diet and
rate of removal by catabolism.
Triglyceride Catabolism:
·
Breakdown
of triglycerides is by lipase to fatty acids and glycerol and then complete
oxidation to form acetyl CoA and energy in a more efficient manner than
glucose. Excess triglyceride catabolism
to fatty acids results in ketone bodies:
acetone, beta-hydrobutyric acid and acetoacetate.
·
Ketone
body excess is formed in liver when glucose levels are low and fatty acid
concentrations are increased. In liver,
ketone bodies cannot be metabolized any further and are secreted into the blood
pool where they are catabolized in muscle and brain cells alongside glucose.
·
Excess
ketone bodies found in the blood are removed by the kidney in form of
ketonuria, which is an indicator of metabolic acidosis, a disorder resulting
from high levels of ketone bodies in the blood.
Classification of Lipoproteins
Classification of Lipoprotein By Density:
·
There
are 5 types of lipoproteins as classified by density:
1.
High density
lipoprotein (HDL)
2.
Low density
lipoprotein (LDL)
3.
Intermediate
density lipoprotein (IDL)
4.
Very low density
lipoprotein (VLDL)
5.
Chylomicrons
(the least dense)
These can also
be classified based on their chemical makeup:
·
High density
lipoprotein:
contains a large amount of protein (apolipoprotein AI and AII), phospholipids
and small amounts of cholesterol ester.
·
Low density lipoprotein: contains less protein and different type
(apolipoprotein B-100), largest amounts of cholesterol and cholesterol ester
and some phospholipids and triglycerides.
·
Very low density lipoprotein: contains less protein, (apolipoprotein B-100,
apolipoprotein C) large amounts of triglycerides and small amounts of
cholesterol
·
Chylomicrons: contains the least amount of proteins
(apolipoprotein B-48, apolipoprotein C) but most amount of triglycerides
Source of Lipoproteins
·
Chylomicrons
are produced in the intestines as packages of dietary fat and absorbed into the
lymphatic system and blood stream to carry dietary fats to the liver.
·
The
liver produces high density lipoprotein and very low density lipoprotein which
circulate.
·
Very
low density lipoproteins are acted upon by peripheral tissues and converted to
intermediate density lipoprotein and low density lipoprotein as triglycerides
are removed and stored in adipose tissue.
·
LDL
is transported back to the liver by high density lipoprotein in reverse
cholesterol transport.
·
The
liver and some endocrine tissues use the cholesterol to make steroid hormones
and vitamins such as vitamin D.
Function
of Lipoproteins
·
General
functions of Lipids:
o
Energy
depot (reserve) especially for triglycerides and fatty acids
o
Structural
component of cell membrane especially for cholesterol and phospholipids
o
Source
of fat soluble factors especially for cholesterol which is an important
building block for bile salts, steroid hormones and vitamin D
·
The
functions of lipoproteins are variable.
lipoproteins
function together to move lipids to the tissues from either the intestine or
the liver, or to move lipids from tissues back to the liver.
·
The
protein portion of the lipoproteins, the apolipoproteins also have variable
functions. For example
o
Apolipoprotein
AI is a cofactor to an important lipid enzyme called LCAT(Lecithin-Cholesterol Acyltransferase)(a Protein Coding gene), while apolipoprotein AIV activated
LCAT.
o
Apolipoprotein
B-100, as associated with LDL and is involved in the LDL receptor binding in
the liver.
Clinical significance of
Lipoprotein in health and diseases (using reference ranges)
Lipoproteins are the
proteins, which mainly transport fats in the blood stream. They can be grouped
into chylomicrons, very low density lipoproteins (VLDL), low density
lipoproteins (LDL) and high density lipoproteins (HDL). Chylomicrons and VLDL
transport mainly triglycerides, though VLDLs also transport some amount of
cholesterol. LDL carries cholesterol to the peripheral tissues where it can be
deposited and increase the risk of arteriosclerotic heart and peripheral
vascular disease. Hence high levels of LDL are atherogenic.
(HDL); transports cholesterol from the peripheral
tissues to the liver for excreation, hence HDL has a protective effect. The
measurement of total and HDL cholesterol and triglycerides provide valuable
information for the risk assessment of coronary heart diseases.
(LDL); The LDL particles are lipoproteins that
transport cholesterol to the cells. Often called “bad cholesterol” because high levels are risk factor for coronary
heart disease and are associated with obesity, diabetes and nephrosis. Clinical
diagnosis should not be made on a single test result; it should integrate
clinical and other laboratory data.
(TRIGLYCERIDE); Increase in serum Triglycerides levels are
seen in cases of liver destruction due to hepatitis, extra hepatic biliary
obstructions as well as cirrhosis. An increase synthesis of VLDL resulting from
diabetes mellitus also plays roll in increase of serum Triglycerides level.
During pregnancy the normal levels of Triglycerides rises up to 40% where as
non specific elevation are seen in the cases of acute pancreatitis, Myocardial
infarction, renal failure and Gout. Serum Triglycerides levels may reduce
during starvation, malnutrition or malabsorption.
o
HDL:
the so-called “good cholesterol”
because it functions to remove low density lipoprotein from circulation and
takes the cholesterol back to the liver to prevent excess accumulation in the
blood vessels.
o
HDL:
is protective for coronary artery
disease and atherosclerosis.
o
There
is a high risk for atherosclerosis and coronary artery disease for HDL levels
below the reference range.
o LDL: the so-called “bad cholesterol” because it carries large amount of cholesterol in circulation but if not removed by the liver due to excess amounts, will cause a high risk for atherosclerosis and coronary artery disease.
Triglyceride:
Reference ranges for adult: 60-170mg/dl
Hyperlipoproteinemia and hypolipoproteinemia
o
Hyperlipidemia is the state of increased
lipids in the blood. Specific types are hypercholesterolemia(increased blood
cholesterol levels) and hypertriglyceridemia(increased
triglyceride levels).
o
Hyperlipoproteinemia is the more correct term
since lipids are transported as lipoproteins in the circulation.
o
Hypercholesterolemia is a genetic disorder of high
blood cholesterol in which the individual develops atherosclerosis in childhood. It is a hyperlipoproteinemia due to a
defective LDL receptor so receptor mediated uptake of cholesterol by LDL does
not occur and Cholesterol is not cleared from blood. This causes accumulated cholesterol forming
atherosclerotic plaques.
o
Endogenous
cholesterol synthesis continues despite excessive cholesterol in blood because
extracellular cholesterol cannot enter cell to regulate intracellular
synthesis.
o
Hyperlipoproteinemia LDL can also occur due to
multiple factors including dietary excess of fats.
o
Hypolipoproteinemia of HDL is decreased HDL in
circulation which also is associated with hypercholesterolemia and
atherosclerosis. It may be due to
genetic disorders of apolipoprotein A (Tangier
disease< is an inherited disorder characterized by significantly reduced
levels of high-density lipoprotein (HDL) in the blood>) or due to secondary
disorders.
Principle of analytical methods
for serum HDL, LDL and triglycerides
Ø Principle of HDL measurement by cholesterol content:
The direct HDL cholesterol assay is a homogenous method for directly measuring serum HDL-C levels without the need for any pretreatment and centrifugation steps. First step, substances with high affinity to LDL, VLDL and chylomicrons block them involving in enzyme reaction. Second step, special surfactant that selectively accelerates reaction of enzyme reagent with HDL cholesterol and determining them.
§ Specimen requirement:
o
Serum
is preferred and should be refrigerated if not analysed within 3 hours.
o
Refrigerated
serum is stable for up to 3 days. Serum not separated from whole blood is
stable in refrigerator for 3 hours.
o
Patient
should be fasting 8 hours.
o
NORMALVALUE
:
Male : 35
- 80 mg/dl
Female : 42 - 88 mg/dl
Ø Principle of LDL measurement
§ Total
cholesterol, triglycerides and HDL-c are measured. LDL-C is calculated by this
formula:
§ LDL-C = Total Cholesterol
– HDL Cholesterol – (TG/2.22) = LDL-C expressed in mmol/L
§ Triglyceride/2.22 is an estimation of VLDL-C, which is based on average ratio of TG: cholesterol in VLDL. This method is inaccurate if triglycerides exceed 4.52 mmol/L
·
LDL
may be measured by a direct method.
o
Precipitate
LDL with polyvinyl sulfate or heparin at low pH
o
LDL-C
= Total cholesterol – supernatant cholesterol measured by cholesterol esterase/
cholesterol oxidase forming quinoneimine dye product with Absorbance measured
at 500 nm.
o
Alternatively,
LDL-C measured in precipitate using the cholesterol esterase/ cholesterol
oxidase method.
·
Specimen
requirement:
o
Serum
is preferred and should be refrigerated if not analysed within 3 hours.
o
Refrigerated
serum is stable for up to 3 days.
o
Serum
not separated from whole blood is stable in refrigerator for 3 hours.
o
Patient
should be fasting 8 hours.
Ø Principle of VLDL measurement by Friedewald
Calculation:
Triglyceride/2.22
is an estimation of VLDL-C which is based on average ratio of TG: cholesterol
in VLDL. This method is inaccurate if
triglycerides exceed 4.52 mmol/L
o
NORMAL VALUE :
< 130 mg/dl Desirable
130 - 159 mg/dL Border line high risk for CHD
> 160 mg/dL High risk for CHD.
Ø Principle of Triglyceride method:
Glycerol released from hydrolysis of
triglycerides by lipoprotein lipase is converted by glycerol kinase into
glycerol-3-phosphate which is oxidized by glycerol phosphate oxidase to
dihydroxyacetone phosphate and hydrogen peroxide. In presence of peroxidase,
hydrogen peroxide oxidizes phenolic chromogenic to a red coloured compound.
·
Beer-Lambert law; states
that there is a linear relationship between the concentration and the
absorbance of the solution, which enables the concentration of a solution to be
calculated by measuring its absorbance.
·
Wavelenght; the distance between successive crests of a
wave, especially points in a sound wave or electromagnetic wave.
Summary
·
There
are 5 main types of lipoproteins: High-density lipoprotein, Low density
lipoprotein, Intermediate density lipoprotein, Very low density lipoprotein and
Chylomicrons.
·
In
addition to total Cholesterol and Triglycerides, HDL and LDL are commonly measured
in a Lipid
Profile to assess risk for coronary heart disease and atherosclerosis.
·
Decreased
HDL and increased total cholesterol and LDL levels in serum compared to their
reference ranges are associated with high risk for atherosclerosis.
Cholesterol
is important because
o
build
the structure of cell membranes.
o
make
hormones like oestrogen, testosterone and adrenal hormones.
o
help
your metabolism work efficiently, for example, cholesterol is essential for
your body to produce vitamin D.
o
produce
bile acids, which help the body digest fat and absorb important nutrients.
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