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.

Nomenclature for stereoisomers: D and L designations are based on the configuration about the single asymmetric carbon in glyceraldehydes

For sugars with more than one chiral center, the D or L designation refers to the asymmetric carbon farthest from the aldehyde or keto group.

Most naturally occurring sugars are D isomers.

D & L sugars are mirror images of one another. They have the same name. For example, D-glucose and L-glucose

Other stereoisomers have unique names, e.g., glucose, mannose, galactose, etc. The number of stereoisomers is 2 ⁿ, where n is the number of asymmetric centers. The six-carbon aldoses have 4 asymmetric centers, and thus 16 stereoisomers (8 D-sugars and 8 L-sugars

An aldehyde can react with an alcohol to form a hemiacetal

Similarly a ketone can react with an alcohol to form a hemiketal

Pentoses and hexoses can cyclize, as the aldehyde or keto group reacts with a hydroxyl on one of the distal carbons

E.g., glucose forms an intra-molecular hemiacetal by reaction of the aldehyde on C1 with the hydroxyl on C5, forming a six-member pyranose ring, named after the compound pyran

The representations of the cyclic sugars below are called Haworth projections.

Fructose can form either: 

• a six-member pyranose ring, by reaction of the C2 keto group with the hydroxyl on C6
• a 5-member furanose ring, by reaction of the C2 keto group with the hydroxyl on C5.

Cyclization of glucose produces a new asymmetric center at C1, with the two stereoisomers called anomers, α & β

Haworth projections represent the cyclic sugars as having essentially planar rings, with the OH at the anomeric C1 extending either:

• below the ring (α)
• above the ring (β).

Because of the tetrahedral nature of carbon bonds, the cyclic form of pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar

Amino Acid Biosynthesis

Glutamate and Aspartate

Glutamate and aspartate are synthesized from their widely distributed a-keto acid precursors by simple 1-step transamination reactions. The former catalyzed by glutamate dehydrogenase and the latter by aspartate aminotransferase, AST. Aspartate is also derived from asparagine through the action of asparaginase. The importance of glutamate as a common intracellular amino donor for transamination reactions and of aspartate as a precursor of ornithine for the urea cycle is described in the Nitrogen Metabolism page.
 

Alanine and the Glucose-Alanine Cycle

Role in protein synthesis,

Alanine is second only to glutamine in prominence as a circulating amino acid.. When alanine transfer from muscle to liver is coupled with glucose transport from liver back to muscle, the process is known as the glucose-alanine cycle. The key feature of the cycle is that in 1 molecule, alanine, peripheral tissue exports pyruvate and ammonia (which are potentially rate-limiting for metabolism) to the liver, where the carbon skeleton is recycled and most nitrogen eliminated.

There are 2 main pathways to production of muscle alanine: directly from protein degradation, and via the transamination of pyruvate by alanine transaminase, ALT (also referred to as serum glutamate-pyruvate transaminase, SGPT).

glutamate + pyruvate <-------> a-KG + alanine

Cysteine Biosynthesis

The sulfur for cysteine synthesis comes from the essential amino acid methionine. A condensation of ATP and methionine catalyzed by methionine adenosyltransferase yields S-adenosylmethionine

Tyrosine Biosynthesis

Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%.

Phenylalanine hydroxylase is a mixed-function oxygenase: one atom of oxygen is incorporated into water and the other into the hydroxyl of tyrosine. The reductant is the tetrahydrofolate-related cofactor tetrahydrobiopterin, which is maintained in the reduced state by the NADH-dependent enzyme dihydropteridine reductase (DHPR).

Ornithine and Proline Biosynthesis

Glutamate is the precursor of both proline and ornithine, with glutamate semialdehyde being a branch point intermediate leading to one or the other of these 2 products. While ornithine is not one of the 20 amino acids used in protein synthesis, it plays a significant role as the acceptor of carbamoyl phosphate in the urea cycle

Serine Biosynthesis

The main pathway to serine starts with the glycolytic intermediate 3-phosphoglycerate. An NADH-linked dehydrogenase converts 3-phosphoglycerate into a keto acid, 3-phosphopyruvate, suitable for subsequent transamination. Aminotransferase activity with glutamate as a donor produces 3-phosphoserine, which is converted to serine by phosphoserine phosphatase.
 

Glycine Biosynthesis

The main pathway to glycine is a 1-step reaction catalyzed by serine hydroxymethyltransferase. This reaction involves the transfer of the hydroxymethyl group from serine to the cofactor tetrahydrofolate (THF), producing glycine and N⁵,N¹⁰-methylene-THF. Glycine produced from serine or from the diet can also be oxidized by glycine cleavage complex, GCC, to yield a second equivalent of N⁵,N¹⁰-methylene-tetrahydrofolate as well as ammonia and CO₂.

Glycine is involved in many anabolic reactions other than protein synthesis including the synthesis of purine nucleotides, heme, glutathione, creatine and serine.

Aspartate/Asparagine and Glutamate/Glutamine Biosynthesis

Glutamate is synthesized by the reductive amination of a-ketoglutarate catalyzed by glutamate dehydrogenase; it is thus a nitrogen-fixing reaction. In addition, glutamate arises by aminotransferase reactions, with the amino nitrogen being donated by a number of different amino acids. Thus, glutamate is a general collector of amino nitrogen.

Aspartate is formed in a transamintion reaction catalyzed by aspartate transaminase, AST. This reaction uses the aspartate a-keto acid analog, oxaloacetate, and glutamate as the amino donor. Aspartate can also be formed by deamination of asparagine catalyzed by asparaginase.

Asparagine synthetase and glutamine synthetase, catalyze the production of asparagine and glutamine from their respective a-amino acids. Glutamine is produced from glutamate by the direct incorporation of ammonia; and this can be considered another nitrogen fixing reaction. Asparagine, however, is formed by an amidotransferase reaction.

Aminotransferase reactions are readily reversible. The direction of any individual transamination depends principally on the concentration ratio of reactants and products. By contrast, transamidation reactions, which are dependent on ATP, are considered irreversible. As a consequence, the degradation of asparagine and glutamine take place by a hydrolytic pathway rather than by a reversal of the pathway by which they were formed. As indicated above, asparagine can be degraded to aspartate

ZINC

The enzyme RNA polymerase, which is required for transcription, contains zinc and it is essential for protein bio synthesis.

Deficiency in Zinc leads to poor wound healing, lesions of skin impaired spermatogenesis, hyperkeratosis, dermatitis and alopecia

PHOSPHOLIPIDS

These are complex or compound lipids containing phosphoric acid, in addition to fatty acids, nitrogenous base and alcohol 

There are two  classes of phospholipids

1. Glycerophospholipids (or phosphoglycerides) that contain glycerol as the alcohol.

2. Sphingophospholipids (or sphingomyelins) that contain sphingosine as the alcohol

Glycerophospholipids

Glycerophospholipids are the major lipids that occur in biological membranes. They consist of glycerol 3-phosphate esterified at its C1 and C2 with fatty acids. Usually, C1 contains a saturated fatty acid while C2 contains an unsaturated fatty acid.

In glycerophospholipids, we refer to the glycerol residue (highlighted red above) as the "glycerol backbone."

Glycerophospholipids are Amphipathic

Glycerophospholipids are sub classified as

1. Phosphatidylethanolamine or cephalin also abbreviated as PE is found in biological membranes and composed of ethanolamine bonded to phosphate group on diglyceride.

2. Phosphatidylcholine or lecithin or PC which has chloline bonded with phosphate group and glycerophosphoric acid with different fatty acids like palmitic or hexadecanoic acid, margaric acid, oleic acid. It is a major component of cell membrane and mainly present in egg yolk and soy beans.

3. Phosphatidic acid (phosphatidate) (PA)

It consists of a glycerol with one saturated fatty acid bonded to carbon-1 of glycerol and an unsaturated fatty acid bonded to carbon-2 with a phosphate group bonded to carbon-3.

4.Phosphatidylserine (PS)

This phospholipid contains serine as an organic compound with other main components of phospholipids. Generally it found on the cytosolic side of cell membranes.

5. Phosphoinositides

It is a group of phospholipids which are negatively charged and act as a a minor component in the cytosolic side of eukaryotic cell membranes. On the basis of different number of phosphate groups they can be different types like phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate(PIP2) and phosphatidylinositol trisphosphate (PIP3). PIP, PIP2 and PIP3 and collectively termed as phosphoinositide.

6. Cardiolipin :

lt is so named as it was first isolated from heart muscle. Structurally, a cardiolipin consists of two molecules of phosphatidic acid held by an additional glycerol through phosphate groups. lt is an important component of inner mitochondrial membrane. Cardiolipin is the only phosphoglyceride that possesses antigenic properties.

Pantothenic Acid

Pantothenic Acid is involved in energy production, and aids in the formation of hormones and the metabolism of fats, proteins, and carbohydrates from food.

RDA The Adequate Intake (AI) for Pantothenic Acid is 5 mg/day for both adult males and females.

Pantothenic Acid Deficiency

Pantothenic Acid deficiency is uncommon due to its wide availability in most foods.