Browsing Pathways

Thioredoxins are a class of proteins that are used in redox reactions, and are found in all living organisms. In humans, they respond to reactive oxygen species, while in plants they are important for growth, photosynthesis, flowering and seed formation. In E. coli, thioredoxins catalyze a number of redox reactions, and are important in stress response, as well as other functions. In this pathway, oxidized thioredoxin is reduced by thioredoxin reductase, in order to form reduced thioredoxin. This reaction also uses NADPH as a cofactor. Reduced thioredoxin then, as part of a redox reaction, acts as the oxidizing agent and converts an oxidized electron acceptor into a reduced electron acceptor. This then produces oxidized thioredoxin, which can be further reduced and reused in other redox reactions.

The TCA cycle (tricarboxylic acid cycle) is also known as the citric acid cycle and the Krebs cycle. This pathway is the catabolism of aerobic respiration which produces energy and reducing power. It also initiates the production of precursors necessary for biosynthesis. If the carbon source for the cycle is acetate then citrate synthase becomes rate-limiting. Respiration produces ATP through a process of compounds acting as electron donors transferring electrons to electron acceptors. During this electron transport chain, a proton motive force is generated by the transport of protons outside the cytoplasmic membrane. As protons return to the cytoplasm, a multisubunit ATPase catalyzes the production of ATP from the proton motive force energy. During aerobic respiration, the final electron acceptor is oxygen. During anaerobic respiration, several organic compounds act as acceptors such as hydrogen, fumarate and nitrate. The cycle can start from Acetyl-CoA interacting with Oxalacetic acid and water through a citrate synthase monomer resulting in a hydrogen ion, CoA and a Citric Acid. The latter compound is dehydrated by a Citrate hydro-lyase resulting in the release of water and a cis-Aconitic acid. This compound is then hydrated through a Citrate hydro-lyase resulting in a D-threo-Isocitric acid. This compound is decarboxylated by an NADP dependent Citrate dehydrogenase, resulting in a release of carbon dioxide and NADPH and Oxoglutaric acid. The oxoglutaric acid interacts with a Coenzyme A through a NAD driven 2-oxoglutarate dehydrogenase resulting in a release of carbon dioxide, an NADH and succinyl-CoA. The succinyl-CoA interacts with a phosphate and an ADP through a 2-oxoglutarate dehydrogenase resulting in a CoA, an ATP and Succinic Acid. Succinic acid interacts with a ubiquinone, in this case a ubiquinone 1 through a succinate:quinone oxidoreductase resulting in an ubiquinol, in this case a ubiquinol-1 and a fumaric acid. The fumaric acid interacts with water through a fumarase hydratase resulting in a L-Malic acid. Malic acid can either react with a NAD dependent dehydrogenase resulting in the release of pyruvate. Malic Acid acid can also react with a malate dehydrogenase resulting in the release of oxalacetic acid

Vitamin B6 is a water-soluble vitamin essential for all living organisms. It is an important cofactor for enzymatic reactions in over one hundred different cellular reactions and processes. Vitamin B6 exists in different natural forms called vitamers, which are produced by plants, bacteria, and fungi, but not by animals and humans. These vitamers include: pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) and their phosphorylated vitamers, PLP, PNP and PMP respectively. Vitamin B6 metabolic pathway was mainly characterized in E. coli, however most organisms, including plants, utilize an alternate pathway. In plants, the various vitamers can be produced via different specific pathways. In A. thaliana, this biosynthetic pathway involves few subpathways, which include: glycolysis, pentose phosphate pathway (PPP), and glyoxylate and dicarboxylate metabolism. Glyceraldehyde 3-phosphate produced by glycolysis and ribulose 5-phosphate produced by PPP are synthesized to pyridoxal 5-phosphate by a synthase. Pyridoxal 5-phosphate is then dephosphorylated to pyridoxal. Pyridoxal, a form of vitamin B6, could act as a precursor for butanoate metabolsim. Moreover, from PPP, 2-Oxo-3-hydroxy-4-phosphobutanoate is produced, this is synthesized to O-phospho-4-hydroxy-L-threonine and then to 4-hydroxy-L-threonine. Pyridoxine could also be produced after a multistep reaction from 4-hydroxy-L-threonine, which is then synthesized to pyridoxal. Glycoaldehyde produced from glyoxylate and dicarboxylate metabolism is converted to pyridoxine. Pyridoxine could also undergo phosphorylation where it is converted to pyridoxine phosphate which is then synthesized to pyridoxal 5-phosphate where the later is dephosphorylated to pyridoxal. Pyridoxal could also be synthesized to pyridoxamine, this that is phosphorylated to pyridoxamin 5-phosphate, which is then synthesized to pyridoxal 5-phosphate.

The methionine metabolism starts from aspartate-produced homoserine. Homoserine reacts with HSK resulting in the release of O-phospho-L-homoserine. The latter compound interacts with cysteine through CGS resulting in the release of phosphate and cystathionine. The latter compound reacts with COI3 resulting in the release of 2-aminoprop-2-enoate, hydrogen ion and homocysteine. Homocysteine can react with S-adenosyl-L-methionine through a HMT protein complex resulting in the release of methionine. Methionine can be used to generate S-adenosyl-L-methionine or it can generate oxobutanoate

Vitamin K describes a group of lipophilic, hydrophobic vitamins that exist naturally in two forms (and synthetically in three others): vitamin K1, which is found in plants, and vitamin K2, which is synthesized by bacteria. Vitamin K is an important dietary component because it is necessary as a cofacter in the activation of vitamin K dependent proteins. Metabolism of vitamin K occurs mainly in the liver. In the first step, vitamin K is reduced to its quinone form by a quinone reductase such as NAD(P)H dehydrogenase. Reduced vitamin K is the form required to convert vitamin K dependent protein precursors to their active states. It acts as a cofactor to the integral membrane enzyme vitamin K-dependent gamma-carboxylase (along with water and carbon dioxide as co-substrates), which carboxylates glutamyl residues to gamma-carboxy-glutamic acid residues on certain proteins, activating them. Each converted glutamyl residue produces a molecule of vitamin K epoxide, and certain proteins may have more than one residue requiring carboxylation. To complete the cycle, the vitamin K epoxide is returned to vitamin K via the vitamin K epoxide reductase enzyme, also an integral membrane protein. The vitamin K dependent proteins include a number of important coagulation factors, such as prothrombin. Thus, warfarin and other coumarin drugs act as anticoagulants by blocking vitamin K epoxide reductase.

Inositol (also known as myo-inositol) is a carbocyclic polyol that can be found in many food such as nuts and beans. Inositol (e.g. inositol phosphates, etc.) can act as secondary messengers in eukaryotic cells. Inositol can be synthesized from three resources: inositol monophosphatase 1 can catalyze D-Myo-inositol 4-phosphate, myo-inositol 1-phosphate and 1D-myo-Inositol 3-phosphate to form inositol with water as cofactor.

The N-glycan biosynthesis is a pathway involving the creation of a dolichol, and the consecutive reactions involving the addition of Acetylglucosaminyl groups, mannosyl groups and glucosyl groups. The set of reactions all happen in the ER membrane. The resulting glucosyl3mannosyl9-N-acetylglucosaminyl2-diphosphodolichol is used as protein modificator.

In the majority of organisms, fatty acid degradation occurs mostly through the beta-oxidation cycle. In plants, this cycle only happens in the peroxisome, while in mammals this cycle happens in both the peroxisomes and mitochondria. Unfortunately, traditional fatty acid oxidation does not work for branched-chain fatty acids, or fatty acids that do not have an even number of carbons, like the fatty acid phytanic acid, found in animal milk. This acid can not be oxidized through beta-oxidation, as problems arise when water is added at the branched beta-carbon. To be able to oxidize this fatty acid, the carbon is oxidized by oxygen, which removes the initial carboxyl group, which shortens the chain. Now lacking a methyl group, this chain can be beta-oxidized. Now moving to the mitochondria, there are four reactions that occur, and are repeated for each molecule of the fatty acid. Each time the cycle of these reactions is completed, the chain is relieved of two carbons, which are oxidized and are taken away by NADH and FADH2, energy carriers that collect the carbons energy. After beta-oxidation in the cycle of reactions, an acetyl-CoA unit is released and is recycled into the cycle of reactions in the mitochondria, until the chain is fully broken down into acetyl-CoA, and can enter the TCA cycle. Once in the TCA cycle, it is converted to NADH and FADH2, which in turn help move along mitochondrial ATP production. Acetyl-CoA also helps produce ketone bodies that are further converted to energy in the heart and the brain.

Isoleucine biosynthesis begins with L-threonine from the threonine biosynthesis pathway. L-threonine interacts with a threonine dehydratase biosynthetic releasing water, a hydrogen ion and (2Z)-2-aminobut-2-enoate. This compound is isomerized into a 2-iminobutanoate which interacts with water and a hydrogen ion spontaneously, resulting in the release of ammonium and 2-ketobutyric acid. This compound reacts with pyruvic acid and hydrogen ion through an acetohydroxybutanoate synthase / acetolactate synthase 2 resulting in carbon dioxide and (S)-2-Aceto-2-hydroxybutanoic acid. The latter compound is reduced by an NADPH driven acetohydroxy acid isomeroreductase releasing NADP and acetohydroxy acid isomeroreductase. The latter compound is dehydrated by a dihydroxy acid dehydratase resulting in 3-methyl-2-oxovaleric acid.This compound reacts in a reversible reaction with L-glutamic acid through a Branched-chain-amino-acid aminotransferase resulting in oxoglutaric acid and L-isoleucine.

The cyanate degradation pathway begins with the transportation of cyanate into the cytosol through a cynX transporter. Once inside the cytosol cyanate reacts with hydrogen carbonate and a hydrogen ion through a cyanase resulting in the release of carbon dioxide and carbamate. Carbamate reacts spontaneously with hydrogen resulting in the release of ammonium and carbon dioxide. Carbon dioxide reacts with water through carbonic anhydrase resulting in the release of hydrogen ion and hydrogen carbonate.