Most fatty acids have even number of carbon atoms and are therefore completely converted to Acetyl-CoA. Some plants and marine organisms, however, synthesize fatty acids with an odd number of carbon atoms. The final round of Beta-Oxidation of these fatty acids forms Propionyl-CoA, which is converted to Succinyl-CoA for entry into the Citric Acid Cycle. Propionyl-CoA can be derived from breakdown of certain amino acids (Isoleucine, Valine and Methionine), but in mammalian cells these pathways exist in mitochondria. Bacteria in the ruminant animal digestive system provide a source of propionate which eventually gets incorporated as odd-numbered fatty acids in milk fats, and this is the major source for human metabolism.   The conversion of[..]

Cysteine, a sulfur-containing amino acid, is indispensable for the survival of virtually all living organisms, from bacteria to higher eukaryotes. This amino acid is implicated in several processes, including the stability, structure, regulation of catalytic activity, and post-translational modification of various proteins. Due to the ability of its thiol group to undergo redox reactions, Cysteine forms the basic building block of all thiol antioxidants, acting as a direct antioxidant and also as a precursor for the biosynthesis of glutathione, trypanothione, or ovothiol. In addition, cysteine is also essential for the synthesis of biomolecules, including coenzyme A, hypotaurine, taurine, and ubiquitous iron-sulphur (Fe-S) clusters, which are involved in electron[..]

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine with the capacity to induce apoptosis. It is enriched in the tumor microenvironment, promotes tumor growth and subverts innate immune responses to cancer cells. TNF is the best studied member of the TNF superfamily. TNF-alpha can bind to two related receptors, TNF receptors 1 and 2 (TNFR1 and TNFR2), which are also used by other, similar ligands. By binding to TNFR1 and TNFR2, TNF activates distinct signaling pathways important for cell proliferation, cell death and immune responses (Ref.1 and 2). TNFR1 is constitutively expressed in most cell types (Ref.3).The default effect of TNF stimulation is to activate the nuclear factor-kappaB (NF-kappaB) pathway and mediate inflammation. TNFR1 mediates the cytotoxic[..]

Synthesis of the Pyrimidines is less complex than that of the Purines, since the base is much simpler. Synthesis of Carbamoyl-P (Carbamoyl Phosphate) is the first reaction of Pyrimidine biosynthesis. Carbamoyl-P is formed from HCO3- (Bicarbonate) and the amide nitrogen of Glutamine by the cytosolic enzyme CPSase (Carbamoyl Phosphate Synthetase). This reaction consumes two molecules of ATP (Adenosine Monophosphate): One provides a phosphate group and the other energizes the reaction. Then condensation of Carbamoyl-P with Asp (Aspartate or L-Aspartate or Aspartic Acid) occurs to form CAA (N-Carbamoyl-L-Aspartate) which is catalyzed by ATCase (Aspartate Carbamoyltransferase). This reaction is the flux-generating step and occurs without need of ATP because Carbamoyl-P is[..]

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine with the capacity to induce apoptosis. It is enriched in the tumor microenvironment, promotes tumor growth and subverts innate immune responses to cancer cells. TNF is the best studied member of the TNF superfamily. TNF-alpha can bind to two related receptors, TNF receptors 1 and 2 (TNFR1 and TNFR2), which are also used by other, similar ligands. By binding to TNFR1 and TNFR2, TNF activates distinct signaling pathways important for cell proliferation, cell death and immune responses (Ref.1 and 2). TNFR2 is typically restricted to certain subpopulations of immune cells such as CD4+ or CD8+ T cells and a few other cell types such as oligodendrocytes and endothelial cells (Ref.3).TNFR2 signaling has significant[..]

UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions such as  CPD  (Cyclobutane-Pyrimidine Dimers) or 6-4PPs (6-4 Pyrimidine Pyrimidone). The most common covalently linked adjoining pyrimidines are TT(Thymine dimers), T-C (Thymine-Cytosine dimers) and C-C (Cytosine-Cytosine dimers). T-T dimers cause kinks in the DNA strand that prevent both replication and transcription of that part of the DNA. Because they block DNA replication (and therefore prevent cells from reproducing), T-T dimers and other forms of UV damage cannot be inherited, and thus do not constitute mutations. Such kinds of DNA damage are known as premutational lesions because they prevent both transcription and replication of the genes in which they are present and[..]

BMPs (Bone morphogenetic proteins) are the members of the transforming growth factor-beta superfamily of secreted signaling molecules [Ref.1]. Transduction of BMP signal involves two types of transmembrane serine/threonine kinase receptors: type I and type II [Ref.1]. BMP2, BMP4, BMP5,BMP6, BMP7, BMP8, BMP9, BMP10, BMP12, BMP13 and BMP14 (Bone morphogenetic protein 2, 4, 5, 6 ,7, 8, 9, 10, 12, 13 and 14) can bind to three type I receptors: BMPR1A (Bone morphogenetic protein receptor, type IA), BMPR1B (Bone morphogenetic protein receptor, type IB) and ALK-2 (Activin A receptor, type I) and two type II receptor, BMPR2A (Bone morphogenetic protein receptor type IIA) and ACTRIIA [Ref.1]. Various antagonists such as, Noggin, Tsg (twisted gastrulation), GREM1, Follistatin[..]

PKC (Protein Kinase-C) is a cyclic nucleotide-independent enzyme that phosphorylates serine and threonine residues in many target proteins. PKC plays a pivotal role in mediating cellular responses to extracellular stimuli involved in proliferation, differentiation, apoptosis, and exocytotic release in a number of non-neuronal systems such as Islet cells, Chromaffin cells and Paramecium. PKC has also been implicated in phosphorylation of several neuronal proteins, which are thought to regulate neurotransmitter release and establish long-term potentiation in memory formation. PKC is not a single enzyme but a family of serine/threonine kinases. At least eleven closely related PKC isozymes have been reported that differ in their structure, biochemical properties, tissue[..]

Alkylating agents are compounds that cause cytotoxic DNA damage as well as collateral mutagenic damage. They work by adding an alkyl group to the guanine base of the DNA molecule and cause breakage of DNA strands. Methylation at the guanine O6 position forms the greatest promutagenic and lethal toxic DNA lesion. O(6)-methylguanine (O6-meG)  is formed in DNA by alkylation of the oxygen atom of guanine, most often by N-nitroso compounds (NOC) and sometimes due to methylation by other compounds such as endogenous S-adenosyl methionine. Several repair pathways like direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. Direct reversal repair eliminates[..]

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[..]

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[..]

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[..]