LIPOPROTIENS

Lipoproteins Consist of a Nonpolar Core & a Single Surface Layer of Amphipathic Lipids

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules .These are oriented so that their polar groups face outward to the aqueous medium. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein,constituting nearly 70% of some HDL and as little as 1% of Chylomicons. Some apolipoproteins are integral and cannot be removed, whereas others can be freely transferred to other lipoproteins.

There  re five types of lipoproteins, namely chylomicrons, very low density lipoproteins(VLDL)  low density lipoproteins (LDL), high density Lipoproteins (HDL) and free fatty acid-albumin complexes.

ESSENTIAL FATTY ACIDS (EFAs) Polyunsaturated FAs,such as Linoleic acid and g(gamma)- Linolenic acid, are ESSENTIAL FATTY ACIDS — we cannot make them, and we need them, so we must get them in our diets mostly from plant sources.

General structure of amino acids

• All organisms use same 20 amino acids.
• Variation in order of amino acids in polypeptides allow limitless variation.
• All amino acids made up of a chiral carbon attached to 4 different groups      

 - hydrogen
 - amino group
 - carboxyl
 - R group: varies between different amino acids

• Two stereoisomers (mirror images of one another) can exist for each amino acid. Such stereoisomers are called enantiomers. All amino acids found in proteins are in the L configuration.
• Amino acids are zwitterions at physiological pH 7.4. ( i.e. dipolar ions). Some side chains can also be ionized

Structures of the 20 common amino acids

• Side chains of the 20 amino acids vary. Properties of side chains greatly influence overall conformation of protein. E.g. hydrophobic side chains in water-soluble proteins fold into interior of protein
• Some side chains are nonpolar (hydrophobic), others are polar or ionizable at physiological pH (hydrophilic).
• Side chains fall into several chemical classes: aliphatic, aromatic, sulfur-containing, alcohols, bases, acids, and amides. Also catagorized as to hydrophobic vs hydrophilic.
• Must know 3-letter code for each amino acid.

Aliphatic R Groups

• Glycine: least complex structure. Not chiral. Side chain small enough to fit into niches too small for other amino acids.
• Alanine, Valine, Leucine, Isoleucine
  • no reactive functional groups      
  • highly hydrophobic: play important role in maintaining 3-D structures of proteins because of their tendency to cluster away from water
• Proline has cyclic side chain called a pyrolidine ring. Restricts geometry of polypeptides, sometimes introducing abrupt changes in direction of polypeptide chain.

Aromatic R Groups

• Phenylalanine, Tyrosine, Tryptophan
  • Phe has benzene ring therefore hydrophobic.  
  • Tyr and Trp have side chains with polar groups, therefore less hydrophobic than Phe.
  • Absorb UV  280 nm. Therefore used to estimate concentration of proteins.

Sulfur-containing R Groups

• Methionine and Cysteine)
  • Met is hydrophobic. Sulfur atom is nucleophilic.
  • Cys somewhat hydrophobic. Highly reactive. Form disulfide bridges and may stabilize 3-D structure of proteins by cross-linking Cys residues in peptide chains.

Side Chains with Alcohol Groups

• Serine and Threonine
  • have uncharged polar side chains. Alcohol groups give hydrophilic character.
  • weakly ionizable.

Basic R Groups

• Histidine, Lysine, and Arginine.
  • have hydrophilic side chains that are nitrogenous bases and positively charged at physiological pH.
  • Arg is most basic a.a., and contribute positive charges to proteins.

Acidic R Groups and their Amide derivatives

• Aspartate, Glutamate
  • are dicarboxylic acids, ionizable at physiological pH. Confer a negative charge on proteins.
• Asparagine, Glutamine
  • amides of Asp and Glu rspectively
  • highly polar and often found on surface of proteins
  • polar amide groups can form H-bonds with atoms in other amino acids with polar side chains.

CLASSIFICATION OF LIPIDS

Lipids are classified as follows:

1. Simple lipids: Esters of fatty acids with various alcohols.

(a) Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state. A long-chain carboxylic acid; those in animal fats and vegetable oils often have 12–22 carbon atoms.

(b) Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols. Waxes are carboxylic acid esters, RCOOR’ ,with long, straight hydrocarbon chains in both R groups

2. Complex lipids: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid.

(a) Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue. They frequently have nitrogen containing bases and other substituents,

Eg  glycerophospholipids the alcohol is glycerol

     sphingophospholipids the alcohol is sphingosine.

(b) Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and carbohydrate. These lipids contain a fatty acid, carbohydrate and nitrogenous base. The alcohol  is sphingosine, hence they are also called as glycosphingolipids. Clycerol  and phosphate  are absent  

e.g., cerebrosides, gangliosides.

(c) Other complex lipids: Lipids such as sulfolipids and aminolipids. Lipoproteins may also be placed in this category.

3. Precursor and derived lipids: These include fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, and ketone bodies, hydrocarbons, lipid soluble vitamins, and hormones. Because they are uncharged, acylglycerols (glycerides), cholesterol, and cholesteryl esters are termed neutral lipids

4. Miscellaneous lipids: These include a large number of compounds possessing the characteristics of lipids e.g., carotenoids, squalene, hydrocarbons such as pentacosane (in bees wax), terpenes etc.

NEUTRAL LIPIDS: The lipids which are uncharged are referred to as neutral lipids. These are mono-, di-, and triacylglycerols, cholesterol and cholesteryl esters.

Sugar derivatives

Sugar alcohol - lacks an aldehyde or ketone. An example is ribitol.

Sugar acid - the aldehyde at C1, or the hydroxyl on the terminal carbon, is oxidized to a carboxylic acid. Examples are gluconic acid and glucuronic acid

Amino sugar - an amino group substitutes for one of the hydroxyls. An example is glucosamine. The amino group may be acetylated.

N-acetylneuraminate, (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH.

Glycosidic bonds: The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compound can join together, splitting out water to form a glycosidic bond.

R-OH + HO-R'   → R-O-R' + H₂O

Disaccharides: Maltose, a cleavage product of starch, is a disaccharide with an α (1→4) glycosidic linkage between the C1 hydroxyl of one glucose and the C4 hydroxyl of a second glucose. Maltose is the α anomer, because the O at C1  points down from the ring.

Cellobiose, a product of cellulose breakdown, is the otherwise equivalent β anomer.  The configuration at the anomeric C1 is β (O points up from the ring). The β(1→4) glycosidic linkage is represented as a "zig-zag" line, but one glucose residue is actually flipped over relative to the other.

Other disaccharides

• Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose and fructose. Because the configuration at the anomeric carbon of glucose is α (O points down from the ring), the linkage is designated α (1→2). The full name is α -D-glucopyranosyl-(1→2) β -D- fructopyranose.
• Lactose, milk sugar, is composed of glucose and galactose with β (→4) linkage → the anomeric hydroxyl of galactose. Its full name is β -D-galactopyranosyl-(1→)- α -D-glucopyranose

Polysaccharides:

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects

Amylose is a glucose polymer with α (1→4) glycosidic linkages, as represented above. The end of the polysaccharide with an anomeric carbon (C1) that is not involved in a glycosidic bond is called the reducing end

Amylopectin is a glucose polymer with mainly α (1→4) linkages, but it also has branches formed by α (1→6) linkages. The branches are generally longer than shown above. The branches produce a compact structure, and provide multiple chain ends at which enzymatic cleavage of the polymer can occur. 

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more α (1→6) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle cells during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose, with β (1→4) linkages. Every other glucose in cellulose is flipped over, due to the β linkages. This promotes intrachain and interchain hydrogen bonds, as well as van der Waals interactions, that cause cellulose chains to be straight and rigid, and pack with a crystalline arrangement in thick bundles called microfibrils.

Glycosaminoglycans (mucopolysaccharides) are polymers of repeating disaccharides. Within the disaccharides, the sugars tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.

Hyaluronate is a glycosaminoglycan with a repeating disaccharide consisting of two glucose derivatives, glucuronate (glucuronic acid) and N-acetylglucosamine. The glycosidic linkages are β(1→3) and β(1→4).

When covalently linked to specific core proteins, glycosaminoglycans form complexes called proteoglycans. Some proteoglycans of the extracellular matrix in turn link non-covalently to hyaluronate via protein domains called link modules. For example, in cartilage multiple copies of the aggrecan proteoglycan bind to an extended hyaluronate backbone to form a large complex Versican, another proteoglycan that binds to hyaluronate, is in the extracellular matrix of loose connective tissues.

Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating glucuronate and N-acetylglucosamine residues. Later, in segments of the polymer, glucuronate residues may be converted to a sulfated sugar called iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated

Heparin, a glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is relatively highly sulfated.

Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane. Proteins involved in signaling and adhesion at the cell surface have been identified that recognize and bind segments of heparan sulfate chains having particular patterns of sulfation

Lectins are glycoproteins that recognize and bind to specific oligosaccharides.

• Concanavalin A and wheat germ agglutinin are plant lectins that have been useful research tools
• Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It associates with cell surface carbohydrates of disease-causing microorganisms, promoting phagocytosis of these organisms as part of the immune response.
• Selectins are integral proteins of the plasma membrane with lectin-like domains that protrude on the outer surface of mammalian cells. Selectins participate in cell-cell recognition and binding.

Polyprotic Acids

• Some acids are polyprotic acids; they can lose more than one proton.

• In this case, the conjugate base is also a weak acid.

• For example: Carbonic acid (H2CO3 ) can lose two protons sequentially.

• Each dissociation has a unique Ka and pKa value.

Ka₁ = [H+ ][HCO₃ ^- ] / [H₂CO₃]

Ka₂ = [H+ ][CO₃ ^-2 ] / [HCO₃^- ] 

Note: (The difference between a weak acid and its conjugate base differ is one hydrogen)