Isoleucine encoded by the codons AUU, AUC, and AUA used in the biosynthesis of proteins. It is a α-amino acid that contains an α-amino group, an α-carboxylic acid group, and a hydrocarbon side chain. It is classified as a non-polar, uncharged (at physiological pH), branched-chain, aliphatic amino acid. Isoleucine is essential in humans, meaning the body cannot synthesize it, and must be ingested in our diet. Isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes in other organisms such as bacteria (Ref.1).The biosynthesis pathway of L-valine and L-isoleucine from L-threonine is a part of the super pathway of branched amino acid biosynthesis that also generates L-leucine. The first enzyme involved in the pathways[..]
In micro-organisms and plants the biosynthesis of aromatic compounds proceeds via the common seven-step aromatic or shikimate pathway to the branch point intermediate chorismate. This intermediate is subsequently converted to the three aromatic amino acids via specific terminal pathways. Many other aromatic compounds are derived either partially or entirely from chorismate or from other pathway intermediates or end products.The first step in the biosynthesis of Chorismate involves PEP (Phosphoenolpyruvate) from glycolysis and E-4-P (Erythrose 4-Phosphate) from the Pentose Phosphate Cycle. These two precursors are condensed and then cyclized to form 3-Dehydroquinate, followed by removal of a water and a reduction step to produce Shikimate. The first cyclic intermediate[..]
Inorganic sulfur in the environment (primarily sulfate, but also sulfur, and sulfite) must undergo fixation to be utilized by organisms. The fixation of sulfate is largely confined to plants and bacteria and biosynthesis of cysteine represents the final step of sulfate assimilation in these organisms. Fixation begins with the formation of PAPS (3'-Phosphoadenosine-5'-Phosphosulfate). PAPS is an activated sulfate compound and an intermediate in all organisms for sulfate esterification, such as the synthesis of chondroitin sulfate. It is formed in a two-step reaction from sulfate ion and two molecules of ATP. In plants, the main pathway of sulfate reduction is via APS (Adenosine-5'-Phosphosulfate) rather than PAPS (i.e. APS can be utilized directly, without[..]
Cholesterol is the common precursor of all steroid hormones and is biosynthesized in many tissues. Steroid hormones are characterized by a common basic structure of cyclopentane-perhydro-phenantrene, a polycyclic complex of 17 carbon atoms forming a four-ring system. Altering a side chain or subsistent group of a cholesterol molecule produces various steroids molecules. Pregnenolone and progesterone are molecules derived from cholesterol (Ref.1&2).Cholesterol is converted to pregnenolone inside the mitochondria by the enzyme CYP11A1 (cytochrome P450 family 11 subfamily A member 1). This conversion is the first step in the synthesis of steroids and is termed as the cholesterol side-chain cleavage reaction. Pregnenolone then passes through the mitochondrial[..]
Threonine is an alcohol-containing amino acid that can not be produced by metabolism and must be taken in the diet. This amino acid plays an important role along with Glycine and Serine in Porphyrin metabolism. Threonine is incorporated into proteins and enzymes at a molar rate of 6 percent compared to the other amino acids. Methionine is the only sulfur-containing amino acid that is essential for mammals and must therefore be derived entirely from the diet. Methionine is an important amino acid that helps to initiate translation of mRNA (messenger RNA) by being the first amino acid incorporated into the N-terminal position of all proteins. This sulfur-containing amino acid is also the source of sulfur for Cysteine in animals and man. In that regard, Methionine is[..]
Phosphatidylcholine (once given the trivial name 'lecithin') is usually the most abundant phospholipid in animal and plants, often amounting to almost 50% of the total, and as such it is the key building block of membrane bilayers. In particular, it makes up a very high proportion of the outer leaflet of the plasma membrane. Phosphatidylcholine is also the principal phospholipid circulating in plasma, where it is an integral component of the lipoproteins, especially the HDL (High Density Lipoprotein). It is a neutral or zwitterionic phospholipid over a pH range from strongly acid to strongly alkaline (Ref.1). There are two mechanisms for the biosynthesis of phosphatidylcholine. Choline itself is not synthesized by animal cells, but is obtained[..]
In bacteria, biosynthesis of arginine proceeds from glutamate in eight enzymatic steps initiated by the acetylation of glutamate by N-Acetyl Glutamate Synthetase. The N-Acetylated intermediates lead to ornithine. The synthesis of ornithine, like that of proline, involves the activation and reduction of the 5-carboxyl group of glutamate. In prokaryotes the pathway of arginine biosynthesis follows two alternative patterns which differ by the strategies used for the removal of the acetyl group and for the control of the metabolite flow along the pathway. Enterobacteriaceae and Bacillaceae use a linear pathway in which the formation of ornithine from N-Acetylornithine is mediated by the hydrolytic enzyme N-acetylornithinase (Ref.1). In these organisms, acetyl glutamate[..]
Asparagine, a non essential amino acid, synthesized form oxaloacetic acid. It is an amide of a amino acid Aspartate. The enzymes ASPG (asparaginase) and ASRGL1 (asparaginase and isoaspartyl peptidase 1) catalyze the hydrolysis of Asparagine to Aspartate and Ammonia. The enzyme GOT1 (glutamic-oxaloacetic transaminase 1) catalyzes the transamination of Aspartate to oxaloacetic acid which can subsequently enter either the TCA cycle or gluconeogenesis. ASPG play a prominent role in chemotherapy, as cancer cells are dependent on the availability of extracellular Asparagine(Ref.1 &2). Aspartate is converted to Asparagine in an ATP-dependent amidotransferase reaction a[..]
Iodide, which is ingested in food and water, is actively concentrated by the thyroid gland, converted to organic iodine by TPO (Thyroid Peroxidase also known as Iodide Peroxidase), and incorporated into tyrosine in intrafollicular thyroglobulin within the colloid at the basal cell surface of the thyroid follicular cell. The tyrosines are iodinated at one (Monoiodotyrosine) or two (Diiodotyrosine) sites and then coupled to form two active hormones, Thyroxine (T4, a Tetra-Iodinated Tyrosine derivative) and Triiodothyronine (T3). Unlike the other endocrine hormones, these are not peptides. They are derived from the amino acid tyrosine. T4 is the major active hormone. In tissues outside the thyroid, particularly in the liver and kidney, T4 is converted to T3, an active[..]
Catecholamine is the common term for the important hormones Norepinephrine (Noradrenaline), Epinephrine (Adrenaline) and Dopamine. Chromaffin cells of the adrenal medulla are the key site of catecholamine synthesis and collections of these cells are also found in heart, liver, kidney, gonads, adrenergic neurons of the postganglionic sympathetic system, and CNS (Central Nervous System). The major product of the adrenal medulla is epinephrine, which constitutes 80% of the catecholamines released from the medulla (Ref.1&2). Tyrosine initiates catecholamine biosynthesis. It is produced in the liver from phenylalanine through the action of phenylalanine hydroxylase. The tyrosine is then transported to catecholamine-secreting neurons where a series of reactions[..]
The carbon skeletons of Methionine, Isoleucine, Threonine and Valine are degraded by pathways that yield Succinyl-CoA (Succinyl-Coenzyme A), an intermediate of the Citric Acid Cycle. Methionine donates its Methyl group to one of several possible acceptors through S-adenosylmethionine and three of its four remaining carbon atoms are converted to the Propionate of Propionyl-CoA, a precursor of Succinyl-CoA. Isoleucine undergoes transamination, followed by oxidative decarboxylation of the resulting Alpha-Keto Acid. The remaining five-carbon skeleton is further oxidized to Acetyl-CoA and Propionyl-CoA (Ref. 3). Valine undergoes transamination and decarboxylation and then a series of oxidation reactions convert the remaining four carbons to Propionyl-CoA (Ref.1). In[..]
Plasmalogens are glycerophospholipids of neural membranes containing vinyl ether bonds. Their synthetic pathway is located in peroxisomes and endoplasmic reticulum. About 20% of mammalian Glycerophospholipids are Plasmalogens. The exact percentage varies both from species to species and from tissue to tissue within a given organisms. While Plamalogens comprise only 0.8% of phospholipids in human liver, they account for 23% of those in human nervous tissue (Ref.1). One of the starting materials for plasmalogen biosynthesis is DHAP (Dihydroxyacetone Phosphate) from glycolysis, which is used to form the glycerol backbone of the plasmalogen. The initial steps of plasmalogen biosynthesis are catalyzed by DHAP-AT (Dihydroxyacetone phosphate Acyltransferase) and[..]
