In this article we will discuss about the Metabolism of the Plasma Lipoproteins:- 1. Role of Lipoproteins 2. Apo lipoproteins 3. Electrophoretic Separation and their Normal Concentration in Human Plasma 4. Formation of Chylomicrons and VLDL 5. Metabolism of LDL 6. Metabolism of HDL 7. Abnormalities 8. Role of Liver 9. Role of Fatty Liver 10. Lipotropic Factor.
Contents:
- Role of Lipoproteins
- Apo lipoproteins
- Electrophoretic Separation of Lipoprotein and their Normal Concentration in Human Plasma
- Formation of Chylomicrons and VLDL
- Metabolism of LDL
- Metabolism of HDL
- Plasma Lipoprotein Abnormalities
- Role of Liver in Lipid Metabolism
- Role of Fatty Liver in Lipid Metabolism
- Lipotropic Factor
1. Role of Lipoproteins:
Five groups of lipoproteins present in plasma exhibit important role in the transport and metabolism of lipids.
These are:
a. Chylomicrons:
Derived from intestinal absorption of triacylglycerol.
b. Very Low Density Lipoproteins (VLDL or Pre-β-lipoproteins):
Mainly derived from the liver for the export of triacylglycerol and also formed from dietary lipids.
c. Low Density Lipoproteins (LDL or β-lipoproteins):
These represent a final stage in the catabolism of VLDL and chylomicrons.
d. High Density Lipoproteins (HDL or α-lipoproteins):
These are involved in VLDL, chylomicrons and cholesterol metabolism.
e. Free Fatty Acids:
These are not classified with the other plasma lipoproteins as their structure is different. These consist of long chain fatty acids attached to serum albumin.
2. Apo lipoproteins:
The lipoproteins contain one or more proteins or polypeptides known as apoprotein.
The Apo proteins in the lipoproteins are present as:
Some lipoproteins are also glycoproteins.
3. Electrophoretic Separation of Lipoprotein and their Normal Concentration in Human Plasma:
a. α-Lipoproteins:
These occupy the α- globulin region after electrophoresis. These contain 45% proteins, 8% triacylglycerol, 20% cholesterol, 27% phospholipids.
Normal concentration: 300 mg%.
b. β-Lipoproteins:
These occupy the β- globulin region after electrophoresis. They contain 46% cholesterol, 23% phospholipids, 10% triacylglycerol. Their concentration increases in atherosclerosis and coronary thrombosis.
Normal concentration: 300 mg%.
c. Pre-β-lipoproteins:
These occupy the region in between a- and P-lipoproteins. These contain low protein, but contain 50% triacylglycerol, fair amount of cholesterol and phospholipids. Their concentration is also increased in atherosclerosis and coronary thrombosis etc.
Normal concentration: 150 mg%.
4. Formation of Chylomicrons and VLDL:
a. Both chylomicrons and VLDL are found in chyle formed by the lymphatic system draining the intestine. VLDL is the vehicle of transport of triacylglycerol from the liver to the extra hepatic tissues.
b. Apoprotein B which is essential for their formation is synthesized by ribosomes in the rough endoplasmic reticulum and is incorporated into lipoproteins in the smooth endoplasmic reticulum which is the main site of synthesis of triacylglycerol, phospholipids and cholesterol. Carbohydrate is added to the lipoproteins found in the Golgi apparatus.
c. Both are released from the intestine or hepatic cell by reverse pinocytosis.
d. Chylomicrons pass into the spaces between the intestinal cells making their way into the lacteals draining the intestine. VLDL are secreted by hepatic parenchymal cells into the space of Disc and then into the hepatic sinusoids.
Catabolism of Chylomicrons and VLDL:
A. Role of lipoprotein lipase clearing factor lipase:
a. It is present in the walls of blood capillaries and also found in the extracts of heart, lung, spleen, lactating mammary gland.
b. Its concentration in the normal blood is less. It is released from the tissues into the circulation following injection of heparin.
c. Phospholipids and apoprotein C-1 1 are required as cofactors for its activity.
d. It hydrolyzes triacylglycerol to mono-acylglycerol through diacylglycerol. The mono-acylglycerol is finally hydrolyzed by mono-acylglycerol hydrolase.
B. Role of liver:
Chylomicron remnants (about half the diameter of parent chylomicrons) are taken by the liver in vivo and by the perfused liver, in which the cholesteryl esters are hydrolyzed and the triacylglycerol, fatty acids are metabolized.
5. Metabolism of LDL:
a. It is formed from VLDL and chylomicrons.
b. It is removed from the circulation by the liver. The half-time of disappearance of apoprotein B in LDL from the circulation is about 2½ — days.
c. Fibroblasts and lymphocytes may degrade LDL in extra hepatic tissues.
6. Metabolism of HDL:
a. It is synthesized and secreted from liver and intestine.
b. Nascent HDL from intestine does not contain apoprotein C but only apoprotein A. Nascent HDL formed by the liver contains apoprotein and free cholesterol. These lipoproteins are similar to the particles found in the plasma of patients with a deficiency of the plasma enzyme lecithin: Cholesterol acyl transferase (LCAT) and in the plasma of patients with obstructive jaundice.
c. The liver and the intestine are the final sites of degradation of HDL Apo proteins.
7. Plasma Lipoprotein Abnormalities:
a. In cases of abnormal hyperlipemia, the concentration of serum VLDL is increased and the concentration of serum HDL may be decreased, increased or normal.
b. In cases of hyperlipemia with marked hypercholesterolemia, serum LDL is increased.
c. Serum LDL has been found to be increased in diabetes mellitus, hypothyroidism, obstructive jaundice, the nephrotic syndrome and in glycogen storage diseases.
d. The concentration of serum LDL and of total serum cholesterol is significantly increased in atherosclerosis.
e. Studies of serum lipoproteins are still of limited clinical value in myocardial infarction, cerebral thrombosis etc.
f. LDL and also VLDL are possible risk factors in studies related to increased susceptibility to ischemic heart disease.
8. Role of Liver in Lipid Metabolism:
a. The liver has active enzyme systems for synthesizing triacylglycerol’s, phospholipids, cholesterol, plasma lipoproteins and for converting fatty acids to ketone bodies.
b. The fatty acids used in the synthesis of liver triacylglycerol are derived from two sources:
(a) From acetyl-CoA derived from carbohydrate,
(b) Uptake of free fatty acids from the circulation.
c. It is the site for the synthesis of bile acids from cholesterol.
d. It is the major site for the oxidation of fatty acids.
e. Feeding of diets high in carbohydrate containing sucrose or fructose, high levels of circulating free fatty acids, ingestion of ethanol and the presence of high level of insulin enhance the synthesis of triacylglycerol and the secretion of VLDL by the liver.
f. It has the enzyme systems for lengthening and shortening of fatty acids and for saturating and de-saturating fatty acids.
g. This organ is chiefly concerned in removal of phospholipids, cholesterol and lipoproteins from the plasma.
h. Hepatic glucokinase increases with the availability of carbohydrate in the diet. This increases glucose incorporation into the liver and hence glycolysis and fatty acid synthesis. The fatty acids are carried to the adipose tissue as triacylglycerol in VLDL.
Starvation diminishes glucokinase and leads to diminished fatty acid synthesis in the liver. The hypoglycemia stimulates growth hormone production which, in turn, stimulates lipolysis. The free fatty acids so liberated from adipose tissue can influence carbohydrate metabolism in the liver where they are broken down with the formation of acetyl-CoA.
The lipolytic effect of growth hormone is also necessary for its protein anabolic action.
9. Role of Fatty Liver in Lipid Metabolism:
Lipid (mainly as triacylglycerol) can accumulate in the liver for the following reasons causing fatty liver:
a. The increased levels of plasma free fatty acids resulting from mobilization of fat from adipose tissue.
b. The hydrolysis of lipoprotein or chylomicron triacylglycerol by lipoprotein lipase in extra hepatic tissues.
c. Increasing amounts of free fatty acids are taken up by the liver and esterified.
d. The production of plasma lipoprotein does not keep pace with the influx of free fatty acids allowing triacylglycerol to accumulate.
e. During starvation and the feeding of high-fat diets, the quantity of triacylglycerol present in the liver is significantly increased.
f. Uncontrolled diabetes mellitus and toxaemia of pregnancy cause fatty appearance and enlargement of the liver.
g. The metabolic block in the synthesis of lipoproteins from lipid and apoprotein.
h. The deficiency of lipotropic factor causes triacylglycerol to accumulate even though only a normal rate of fatty acid synthesis and uptake of free fatty acids take place.
i. Carbon tetrachloride, chloroform, phosphorus, lead, arsenic and ethionine (α- amino-γ-ethyl-mercaptobutyric acid) cause fatty liver. These substances inhibit hepatic protein synthesis. Orotic acid blocks apo-B synthesis.
j. Alcoholism also leads to fat accumulation in the liver, hyperlipidemia and ultimately cirrhosis.
k. Protein deficiency, essential fatty acid and vitamin deficiencies (e.g., vitamin E, pyridoxine, pantothenic acid) cause fatty liver. The deficiency of essential fatty acids depresses the synthesis of phospholipids and, therefore, cholesterol is involved in esterification causing fatty livers.
10. Lipotropic Factor:
The substances that prevent the accumulation of fat in the liver are known as lipotropic factor. The phenomenon is said to be lipotropism.
Choline, methionine and betaine and β- propiothetin act as lipotropic agents in curing fatty livers due to choline deficiency. Diets poor in protein (containing methionine) or lecithin (containing choline) tend to favour the production of fatty liver. Choline is synthesized using labile methyl groups donated by methionine in the process of trans-methylation.
Vitamin B12 and folic acid which are important in hematopoiesis are also able to produce lipotropic effect. Vitamin B12 is concerned in the biosynthesis of labile methyl groups and folic acid in trans-methylation reactions. Inositol exerts a limited lipotropic effect in fat free diets. Casein and certain other proteins possess lipotropic activity.