Browsing Pathways

The citric acid cycle, which is also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle, is a series of enzyme-catalyzed chemical reactions of key importance in all living cells that use oxygen as part of cellular respiration. In eukaryotes, the citric acid cycle occurs in the mitochondrial matrix. The TCA cycle begins with acetyl-CoA transferring its two-carbon acetyl group to the four-carbon acceptor compound (oxaloacetate) to form a six-carbon compound (citrate). The citrate then goes through a series of chemical transformations, losing first one, then a second carboxyl group as CO2. The carbons lost as CO2 originate from what was oxaloacetate, not directly from acetyl-CoA. The carbons donated by acetyl-CoA become part of the oxaloacetate carbon backbone after the first turn of the citric acid cycle. Loss of the acetyl-CoA-donated carbons as CO2 requires several turns of the citric acid cycle. However, because of the role of the citric acid cycle in anabolism, they may not be lost since many TCA cycle intermediates are also used as precursors for the biosynthesis of other molecules. Most of the energy made available by the oxidative steps of the cycle is transferred as energy-rich electrons to NAD+, forming NADH. For each acetyl group that enters the citric acid cycle, three molecules of NADH are produced. At the end of each cycle, the four-carbon oxaloacetate has been regenerated, and the cycle continues.

Isoniazid is an antibiotic drug used to treat tunerculosis, as well as other types of mycobacteria. Through a currently unknown reaction that may be spontaneous or enzymatic, pyruvic acid or oxoglutaric acid can undergo a dehydration reaction with isoniazid, forming isoniazid pyruvate or isoniazid alpha-ketoglutaric acid. Isoniazid may also react with hydrogen peroxide in the lysosome, forming an isonicotinoyl radical catalyzed by myeloperoxidase. The isonicotinoyl radical can then have either NAD or NADP added in a non-enzymatic reaction, forming isonicotinoyl-NAD and NADP adducts. Isoniazid can have an acetyl group added to it by arylamine N-acetyltransferase 2, fvorming acetylisoniazid. This can then enter the endoplasmic reticulum and, with the addition of a water molecule, can form isonicotinic acid and acetylhydrazine. Isoniazid can also be converted to hydrazine and isonicotinic acid via the same reaction, and the hydrazine can have an acetyl group added to it by arylamine N-acetyltransferase 2 in order to form acetylhydrazine. Acetylhydrazine can have another acetyl group added to it by arylamine N-acetyltransferase 2 to form diacetylhydrazine which is then excreted. It can alternatively be processed by cytochrome P450 2E1 into hepatotoxins, which are then joined to glutatione by glutatione S-transferase omega-2 to form R-S-glutatione, which is then excreted. Finally, isonicotinic acid can react with a glycine in an unclear reaction, potentially requiring ATP and coenzyme A and forming an intermediate, producing isonicotinylglycine, which is also excreted.

Choline is oxidizied in the liver to betaine by choline dehydrogenase (CHDH) or betaine aldehyde dehydrogenase (ALDH7A1). Betaine plays an important role in one carbon metabolism as a methyl donor, which converts homocysteine to methionine. Hence, it augments folate cycle and helps to maintain DNA stability. Betaine is converted to dimethylglycine by betaine-homocysteine S-methyltransferase enzymes (BHMT, BHMT2). Betaine-homocysteine S-methyltransferase enzymes also converts homocysteine to methionine simultaneously. Catabolism by gut microbiome converts choline to trimethylamine, which is then converted to trimethylamine N-oxide (TMAO) by Flavin monooxygenase Isoform (FMO3). Plasma folate is converted to 5-methyl THF . 5-methyl THF is converted to THF by vitamin B12 and the enzymes MTRR and MTR . MTR convertes Homocyteine to Methionine. 5,10-methylene THF is conerted to THF by vitamin B6. 5,10-methylene THF is converted back to 5-methyl THF by MTHFR. 5,10-methylene THFis converted to 5,10-Methenyl THF by MTHFD1, 5,10-Methenyl THF is converted to 10-Formyl THF by MTHFD1, 10-Formyl THF is converted to Formate by MTHFD1. Formate is then converted to THF by Anabolism in Mitochondria.

Abciximab or Abcixifiban is a platelet aggregation inhibitor drug sold under the name ReoPro. It is administered intravenously, and can act to decrease platelet aggregation for up to two days after administration. Abciximab is an antigen binding fragment that targets glycoprotein IIb/IIIa receptors on the outer membrane of platelets. In the vein, Abciximab causes a conformational change in the integrins on the surface of activated platelets. This prevents the binding of fibrinogen to these integrins, which in turn prevents the platelets from being held together by these fibrinogen fibres. The conformational change also prevents the binding of von Willebrand factor to the platelets, which also prevents aggregation and adhesion.

The biosynthesis of phosphoribosyl pyrophosphate begins with a product of the pentose phosphate, D-ribose 5-phosphate interact with a phosphopentomutase resulting in a Ribose 1-phosphate or it can be phosphorylated through an ATP driven ribose-phosphate diphosphokinase resulting in a release of a hydrogen ion, an AMP and a phosphoribosyl pyrophosphate. The latter compound is then involved in the purine nucleotides de novo biosynthesis pathway. Ribose 1-phosphate can interact spontaneously with ATP resulting in a release of hydrogen ion, ADP and a ribose 1,5-biphosphate. The latter compound is then phosphorylated through a ribose 1,5-bisphosphokinase resulting in the release of ADP and phosphoribosyl pyrophosphate. The latter compound is then involved in the purine nucleotides de novo biosynthesis pathway.