KBP Chemistry of Lipids (lanjutan)

3-Gangliosides:

• •They are more complex glycolipids that occur in the gray matter of the brain, ganglion cells, and RBCs.  They transfer biogenic amines across the cell membrane and act as a cell membrane receptor.
• • Gangliosides contain sialic acid (N-acetylneuraminic acid), ceramide (sphingosine + fatty acid of 18-24 carbon atom length), 3 molecules of hexoses (1 glucose + 2 galactose) and hexosamine. The most simple type of it the monosialoganglioside,.  It works as a receptor for cholera toxin in the human intestine.

C-Lipoproteins

• Definition: Lipoproteins are lipids combined with proteins in the tissues.  The lipid component is phospholipid, cholesterol or triglycerides.  The holding bonds are secondary bonds.
• They include:

1.Structural lipoproteins: These are widely distributed in tissues being present in cellular and subcellular membranes. In lung tissues acting as a surfactant in a complex of a protein and lecithin.  In the eye, rhodopsin of rods is a lipoprotein complex.

• Transport lipoproteins:
• These are the forms present in blood plasma. They are composed of a protein called apolipoprotein and different types of lipids. (Cholesterol, cholesterol esters, phospholipids and triglycerides). As the lipid content increases, the density of plasma lipoproteins decreases. 
• Plasma lipoproteins can be separated by two methods: 

1. Ultra-centrifugation: Using the rate of floatation in sodium chloride solution leading to their sequential separation into chylomicrons, very low density lipoproteins (VLDL or pre-b-lipoproteins), low density lipoproteins (LDL or b-lipoproteins), high density lipoproteins (HDL or a-lipoproteins) and albumin-free fatty acids complex. 
2. Electrophoresis: is the migration of charged particles in an electric field either to the anode or to the cathode. It sequentially separates the lipoproteins into chylomicrons, pre-b-, b-, and a-lipoprotein and albumin-free fatty acids complex.

 Structure of a plasma lipoprotein complex

ket: 

1. Polar lipids (phospholipids)
2. Polar apolipoproteins
3. Nonpolar lipids (cholesterol and its esters and triacylglycerols)

a) Chylomicrons: They have the largest diameter and the least density. They contain 1-2% protein only and 98-99% fat. The main lipid fraction is triglycerides absorbed from the intestine and they contain small amounts of the absorbed cholesterol and phospholipids.

b) Very low-density lipoproteins (VLDL) or pre-b-lipoproteins: Their diameter is smaller than chylomicrons. They contain about 7-10% protein and 90-93% lipid. The lipid content is mainly triglycerides formed in the liver. They contain phospholipid and cholesterol more than chylomicrons.

c) Low-density lipoproteins (LDL) or b-lipoproteins: They contain 10-20% proteins in the form of apolipoprotein B.   Their lipid content varies from 80-90%. They contain about 60% of total blood cholesterol and 40% of total blood phospholipids. As their percentage increases, the liability to atherosclerosis increases.

d) High-density lipoproteins (HDL) or a-Lipoproteins: They contain 35-55% proteins in the form of apolipoprotein A. They contain 45-65% lipids formed of cholesterol (40% of total blood content) and phospholipids (60% of total blood content). They act as cholesterol scavengers, as their percentage increases, the liability to atherosclerosis decreases. They are higher in females than in males. Due to their high protein content they possess the highest density.

e) Albumin-free fatty acids complex: It is a proteolipid complex with 99% protein content associated with long-chain free fatty acids for transporting them.

Cholesterol:

•Importance: -

• It is the most important sterol in animal tissues as free alcohol or in an esterified form (with linoleic, oleic, palmitic acids or other fatty acids).
• Steroid hormones, bile salts and vitamin D are derivatives from it.
• Tissues contain different amounts of it that serve a structural and metabolic role, e.g., adrenal cortex content is 10%, whereas, brain is 2%, others 0.2-0.3%.

•Source: 

• It is synthesized in the body from acetyl-CoA (1gm/day, cholesterol does not exist in plants) and is also taken in the diet (0.3 gm/day as in, butter, milk, egg yolk, brain, meat and animal fat).

Physical propeties 

It has a hydroxyl group on C3, a double bond between C5 and C6, 8 asymmetric carbon atoms and a side chain of 8 carbon atoms. 

•It is found in all animal cells, corpus luteum and adrenal cortex, human brain (17% of the solids). 

•In the blood (the total cholesterol amounts about 200 mg/dL of which 2/3 is esterified, chiefly to unsaturated fatty acids while the remainder occurs as the free cholesterol.   

Chemical properties Intestinal bacteria reduce cholesterol into coprosterol and 

 dihydrocholesterol.

•      It is also oxidized into 7-Dehydrocholesterol and further unsaturated cholesterol with a second double bond between C7 and C8.  When the skin is irradiated with ultraviolet light 7-dehydrocholesterol is converted to vitamin D3.  This explains the value of sun light in preventing rickets.

•         Ergosterol differs from 7-dehydrocholesterol in the side chain. Ergosterol is converted to vitamin D2 by irradiation with UV Ergosterol and 7- dehydrocholesterol are called Pro-vitamins D or precursors of vitamin D. 
•         It was first isolated from ergot, a fungus then from yeast.  Ergosterol is less stable than cholesterol (because of having 3 double bonds).

 

 

Steroids

•Steroids constitute an important class of biological compounds.

• Steroids are usually found in association with fat. They can be separated from fats after saponification since they occur in the unsaponifiable residue.

• They are derivatives of cholesterol that is formed of steroid ring or nucleus.

•Biologically important groups of substances, which contain this ring, are:

1.Sterols. 

2.Adrenal cortical hormones.

3.Male and female sex hormones. 

4.Vitamin D group.

5.Bile acids. 

6.Cardiac glycosides.

                 •General consideration about naturally occurring steroids:

A typical member of this group is cholesterol. Certain facts have to be considered when drawing steroid formula:

1) There is always oxygen in the form of hydroxyl or ketone on C3.

2) Rings C and D are saturated (stable).

3) Methyl groups at C18 C19.   In case of vitamin D, the CH3 group at C19 becomes a  

methylene group (=CH2) and the ring B is opened, whereas, this methyl group is absent in 

female sex hormones (estrogens).

4) In estrogens (female sex hormones) ring A is aromatic and there is no methyl group on 

C10.

•Bile acids:

•They are produced from oxidation of cholesterol in the liver producing cholic and chenodeoxycholic acids that are conjugated with glycine or taurine to produce glycocholic, glycochenodeoxycholic, taurocholic and taurochenodeoxycholic acids.  They react with sodium or potassium to produce sodium or potassium bile salts.

•Their function is as follows:

1.Emulsification of lipids during digestion.

2.Help in digestion of the other foodstuffs.

3.Activation of pancreatic lipase.

4.Help digestion and absorption of fat-soluble vitamins.

5.Solubilizing cholesterol in bile and prevent gall stone formation.

6.Choleretic action (stimulate their own secretion).

7.Intestinal antiseptic that prevent putrefaction

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