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Pyrimidine Metabolism
Pyrimidine biosynthesis occurs both in the body and through organic synthesis. ''De novo'' biosynthesis of pyrimidine ''De Novo'' biosynthesis of a pyrimidine is catalyzed by three gene products CAD, DHODH and UMPS. The first three enzymes of the process are all coded by the same gene in CAD which consists of carbamoyl phosphate synthetase II, aspartate carbamoyltransferase and dihydroorotase. Dihydroorotate dehydrogenase (DHODH) unlike CAD and UMPS is a mono-functional enzyme and is localized in the mitochondria. UMPS is a bifunctional enzyme consisting of orotate phosphoribosyltransferase (OPRT) and orotidine monophosphate decarboxylase (OMPDC). Both, CAD and UMPS are localized around the mitochondria, in the cytosol. In Fungi, a similar protein exists but lacks the dihydroorotase function: another protein catalyzes the second step. In other organisms (Bacteria, Archaea and the other Eukaryota), the first three steps are done by three different enzymes. Pyrimidine cata ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carbamoyl Phosphate Synthetase II
Carbamoyl phosphate synthetase (glutamine-hydrolysing) () is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria). Its systemic name is ''hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)''. In pyrimidine biosynthesis, it serves as the rate-limiting enzyme and catalyzes the following reaction: : 2 ATP + L-glutamine + HCO3− + H2O \rightleftharpoons 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction) : (1a) L-glutamine + H2O \rightleftharpoons L-glutamate + NH3 : (1b) 2 ATP + HCO3− + NH3 \rightleftharpoons 2 ADP + phosphate + carbamoyl phosphate It is activated by ATP and PRPP and it is inhibited by UMP (Uridine monophosphate, the end product of the pyrimidine synthesis pathway). Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions. It is one of the three enzyme functions coded by the CA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Uridine 5'-triphosphate
Uridine-5′-triphosphate (UTP) is a pyrimidine nucleoside triphosphate, consisting of the organic base uracil linked to the 1′ carbon of the ribose sugar, and esterified with tri-phosphoric acid at the 5′ position. Its main role is as substrate for the synthesis of RNA during transcription. UTP is the precursor for the production of CTP via the help of CTP Synthetase. UTP can be biosynthesized from UDP by Nucleoside Diphosphate Kinase after using phosphate group from ATP. UDP + ATP ⇌ UTP + ADP; both UTP and ATP are energetically equal. The homologue in DNA is thymidine triphosphate (TTP or dTTP). UTP also has a deoxyribose form (dUTP). Role in metabolism UTP also has the role of a source of energy or an activator of substrates in metabolic reactions, like that of ATP, but more specific. When UTP activates a substrate (like Glucose-1-phosphate), UDP-glucose is formed and inorganic phosphate is released. UDP-glucose enters the synthesis of glycogen. UTP is used in the meta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep biosphere of Earth's crust. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of dead bodies; bacteria are responsible for the putrefaction stage in this process. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Bacteria also live in symbiotic and parasitic relationsh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from the other eukaryotic kingdoms, which by one traditional classification include Plantae, Animalia, Protozoa, and Chromista. A characteristic that places fungi in a different kingdom from plants, bacteria, and some protists is chitin in their cell walls. Fungi, like animals, are heterotrophs; they acquire their food by absorbing dissolved molecules, typically by secreting digestive enzymes into their environment. Fungi do not photosynthesize. Growth is their means of mobility, except for spores (a few of which are flagellated), which may travel through the air or water. Fungi are the principal decomposers in ecological systems. These and other differences place fungi in a single group of related organisms, named the ''Eumycota'' (''t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orotidine 5'-phosphate Decarboxylase
Orotidine 5'-phosphate decarboxylase (OMP decarboxylase) or orotidylate decarboxylase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the decarboxylation of orotidine monophosphate (OMP) to form uridine monophosphate (UMP). The function of this enzyme is essential to the de novo biosynthesis of the pyrimidine nucleotides uridine triphosphate, cytidine triphosphate, and thymidine triphosphate. OMP decarboxylase has been a frequent target for scientific investigation because of its demonstrated extreme catalytic efficiency and its usefulness as a selection marker for yeast strain engineering. Catalysis OMP decarboxylase is known for being an extraordinarily efficient catalyst capable of accelerating the uncatalyzed reaction rate by a factor of 1017. To put this in perspective, the uncatalysed reaction which would take ''78 million years'' to convert half the reactants into products is accelerated to ''18 milliseconds'' when catalyzed by OMP decarboxylase. This ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orotate Phosphoribosyltransferase
Orotate phosphoribosyltransferase (OPRTase) or orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. In yeast and bacteria, orotate phosphoribosyltransferase is an independent enzyme with a unique gene coding for the protein, whereas in mammals and other multicellular organisms, the catalytic function is carried out by a domain of the bifunctional enzyme UMP synthase (UMPS). Biological background As OPRTase is part of a bifunctional complex UMP synthase in humans, the function and stability of this enzyme is not necessarily directly associated with disorders in the human body. It is however reasonable to believe that a dysfunction in one of the enzymes will cause a dysfunction of the whole enzyme. Defects in UMP synthase is associated with hypochromic anemia. In mammals, this bifunctional enzyme UMPS converts orotic acid into uridine ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Uridine Monophosphate Synthetase
The enzyme Uridine monophosphate synthase (, UMPS) (orotate phosphoribosyl transferase and orotidine-5'-decarboxylase) catalyses the formation of uridine monophosphate (UMP), an energy-carrying molecule in many important biosynthetic pathways. In humans, the gene that codes for this enzyme is located on the long arm of chromosome 3 (3q13). Structure and function This bifunctional enzyme has two main domains, an orotate phosphoribosyltransferase (OPRTase, ) subunit and an orotidine-5’-phosphate decarboxylase (ODCase, ) subunit. These two sites catalyze the last two steps of the de novo uridine monophosphate (UMP) biosynthetic pathway. After addition of ribose-P to orotate by OPRTase to form orotidine-5’-monophosphate (OMP), OMP is decarboxylated to form uridine monophosphate by ODCase. In microorganisms, these two domains are separate proteins, but, in multicellular eukaryotes, the two catalytic sites are expressed on a single protein, uridine monophosphate synthase. UMPS exi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dihydroorotate Dehydrogenase
Dihydroorotate dehydrogenase (DHODH) is an enzyme that in humans is encoded by the ''DHODH'' gene on chromosome 16. The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in '' de novo'' pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane (IMM). Inhibitors of this enzyme are used to treat autoimmune diseases such as rheumatoid arthritis. Structure DHODH can vary in cofactor content, oligomeric state, subcellular localization, and membrane association. An overall sequence alignment of these DHODH variants presents two classes of DHODHs: the cytosolic Class 1 and the membrane-bound Class 2. In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, whereas in Class 2, the serine serves this catalytic function. Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms hom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aspartate Carbamoyltransferase
Aspartate carbamoyltransferase (also known as aspartate transcarbamoylase or ATCase) catalyzes the first step in the pyrimidine biosynthetic pathway (). In ''E. coli'', the enzyme is a multi- subunit protein complex composed of 12 subunits (300 kDa in total). The composition of the subunits is C6R6, forming 2 trimers of catalytic subunits (34 kDa) and 3 dimers of regulatory subunits (17 kDa). The particular arrangement of catalytic and regulatory subunits in this enzyme affords the complex with strongly allosteric behaviour with respect to its substrates. The enzyme is an archetypal example of allosteric modulation of fine control of metabolic enzyme reactions. ATCase does not follow Michaelis–Menten kinetics. Instead, it lies between its low-activity, low-affinity "tense" and its high-activity, high-affinity "relaxed" states. The binding of substrate to the catalytic subunits results in an equilibrium shift towards the R state, whereas binding of CTP to the regulatory subu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carbamoyl Phosphate Synthase II
Carbamoyl phosphate synthetase (glutamine-hydrolysing) () is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria). Its systemic name is ''hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)''. In pyrimidine biosynthesis, it serves as the rate-limiting enzyme and catalyzes the following reaction: : 2 ATP + L-glutamine + HCO3− + H2O \rightleftharpoons 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction) : (1a) L-glutamine + H2O \rightleftharpoons L-glutamate + NH3 : (1b) 2 ATP + HCO3− + NH3 \rightleftharpoons 2 ADP + phosphate + carbamoyl phosphate It is activated by ATP and PRPP and it is inhibited by UMP (Uridine monophosphate, the end product of the pyrimidine synthesis pathway). Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions. It is one of the three enzyme functions coded by the CA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CAD (protein)
CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) is a trifunctional multi-domain enzyme involved in the first three steps of pyrimidine biosynthesis. De-novo synthesis starts with cytosolic carbamoylphosphate synthetase II which uses glutamine, carbon dioxide and ATP. This enzyme is inhibited by uridine triphosphate (feedback inhibition). In 2015, the first observed pathological mutations of ''CAD'' were found in a four-year-old boy. CAD protein has been observed in the mid-piece of mammalian spermatozoa, among the mitochondria. Structure CAD protein has a molecular weight of 243 KDa. It is a polypeptide made up of four different domains which make for a multi enzyme unit: Glutaminase (GLN), carbamoyl phosphate synthetase (CPS II), Dihydroorotase (DHO) and aspartate transcarbamoylase (ATC). The protein assembles into ~1.5MDa hexamers. More specifically, the DHO domain assembles into dimers, and ATC domains do so into trimers. The h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine (nitrogen atoms at the 1 and 4 positions) and pyridazine (nitrogen atoms at the 1 and 2 positions). In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U). Occurrence and history The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879, when Grimaux reported the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
