|
Orotic Aciduria
Orotic aciduria (AKA hereditary orotic aciduria) is a disease caused by an enzyme deficiency resulting in a decreased ability to synthesize pyrimidines. It was the first described enzyme deficiency of the ''de novo'' pyrimidine synthesis pathway. Orotic aciduria is characterized by excessive excretion of orotic acid in urine because of the inability to convert orotic acid to UMP. It causes megaloblastic anemia and may be associated with mental and physical developmental delays. Signs and symptoms Patients typically present with excessive orotic acid in the urine, failure to thrive, developmental delay, and megaloblastic anemia which cannot be cured by administration of vitamin B12 or folic acid. Cause and genetics This autosomal recessive disorder is caused by a deficiency in the enzyme UMPS, a bifunctional protein that includes the enzyme activities of OPRT and ODC. In one study of three patients, UMPS activity ranged from 2-7% of normal levels. Two types of orotic acidur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orotic Acid
Orotic acid is a pyrimidinedione and a carboxylic acid. Historically, it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin. The compound is synthesized in the body via a mitochondrial enzyme, dihydroorotate dehydrogenase or a cytoplasmic enzyme of Pyrimidine metabolism, pyrimidine synthesis pathway. It is sometimes used as a mineral carrier in some dietary supplements (to increase their bioavailability), most commonly for lithium orotate. Synthesis Dihydroorotate is synthesized to orotic acid by the enzyme dihydroorotate dehydrogenase, where it later combines with phosphoribosyl pyrophosphate (PRPP) to form Orotidine 5'-monophosphate, orotidine-5'-monophosphate (OMP). A distinguishing characteristic of pyrimidine synthesis is that the pyrimidine ring is fully synthesized before being attached to the ribose sugar, whereas purine synthesis happens by building the base directly on the sugar. Chemistry Orotic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autosomal Recessive - En
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes is collectively known as atDNA or auDNA. For example, humans have a diploid genome that usually contains 22 pairs of autosomes and one allosome pair (46 chromosomes total). The autosome pairs are labeled with numbers (1–22 in humans) roughly in order of their sizes in base pairs, while allosomes are labelled with their letters. By contrast, the allosome pair consists of two X chromosomes in females or one X and one Y chromosome in males. Unusual combinations of XYY, XXY, XXX, XXXX, XXXXX or XXYY, among other Salome combinations, are known to occur and usually cause developmental abnormalities. Autosomes still contain sexual determination genes even though they are not sex chromosomes. For example, the SRY gene on the Y chromosome e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Uridine Triacetate
Uridine triacetate (INN), formerly known as vistonuridine, is an orally active tri-acetylated prodrug of uridine used: * in the treatment of hereditary orotic aciduria (brand name Xuriden ); * to treat people following an overdose of chemotherapy drugs 5-fluorouracil (5-FU) or capecitabine regardless of the presence of symptoms, or who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration (brand name Vistogard). Uridine triacetate was developed, manufactured and distributed by Wellstat Therapeutics. It was granted breakthrough therapy designation by the U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Depar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Uridine Monophosphate
Uridine monophosphate (UMP), also known as 5′-uridylic acid (conjugate base uridylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase uracil; hence, it is a ribonucleotide monophosphate. As a substituent or radical its name takes the form of the prefix uridylyl-. The deoxy form is abbreviated dUMP. Covalent attachment of UMP (e.g. to a protein such as adenylyltransferase) is called uridylylation (or sometimes uridylation). Biosynthesis Uridine monophosphate is formed from Orotidine 5'-monophosphate (orotidylic acid) in a decarboxylation reaction catalyzed by the enzyme orotidylate decarboxylase. Uncatalyzed, the decarboxylation reaction is extremely slow (estimated to occur on average one time per 78 million years). Adequately catalyzed, the reaction takes place once per second, an increase of 1017-fold. In humans, the orotidyl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Archives Of Disease In Childhood
''Archives of Disease in Childhood'' is a peer-reviewed medical journal published by the BMJ Group and covering the field of paediatrics. It is the official journal of the Royal College of Paediatrics and Child Health. Scope ''Archives of Disease in Childhood'' focuses on all aspects of child health and disease from the perinatal period through to adolescence. It includes original research reports, commentaries, reviews of clinical and policy issues, and evidence reports. Other sections include: guidelines updates, international health, and a column written by patients about their experience with the health care system. Douglas Gairdner served as editor from 1964 to 1979 and because of his creative editing, he was awarded the Dawson-Williams prize of the British Medical Association. Abstracting and indexing The journal is indexed on MEDLINE/Index Medicus, Web of Science, and Excerpta Medica. According to the ''Journal Citation Reports'', the journal has a 2017 impact factor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hyperammonemia
Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammonia is a substance that contains nitrogen. It is a product of the catabolism of protein. It is converted to the less toxic substance urea prior to excretion in urine by the kidneys. The metabolic pathways that synthesize urea involve reactions that start in the mitochondria and then move into the cytosol. The process is known as the urea cycle, which comprises several enzymes acting in sequence. It is greatly exacerbated by common zinc deficiency, which raises ammonia levels further. Signs and symptoms Complication Hyperammonemia is one of the metabolic derangements that contribute to hepatic encephalopathy, which can cause swelling of astrocytes and stimulation of NMDA receptors in the brain. Overstimulation of NMDA receptors induces excitotoxicity. Diagnosis Types Primary vs. secon ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Blood Urea Nitrogen
Blood urea nitrogen (BUN) is a medical test that measures the amount of urea nitrogen found in blood. The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain 6 to 20 mg/dL (2.1 to 7.1 mmol/L) of urea nitrogen. Individual laboratories will have different reference ranges as the assay used can vary between laboratories. The test is used to detect renal problems. It is not considered as reliable as creatinine or BUN/creatinine ratio blood studies. Interpretation BUN is an indication of renal (kidney) health. The normal range is 2.1–7.1 mmol/ L or 6–20 mg/ dL. The main causes of an increase in BUN are: high protein diet, decrease in glomerular filtration rate (GFR) (suggestive of kidney failure), decrease in blood volume (hypovolemia), congestive heart failure, gastrointestinal hemorrhage, fever, rapid cell destruction from infections, athletic activity, excessive muscle breakdown, and increased ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ornithine Transcarbamylase Deficiency
Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females. In severely affected individuals, ammonia concentrations increase rapidly causing ataxia, lethargy and death without rapid intervention. OTC deficiency is diagnosed using a combination of clinical findings and biochemical testing, while confirmation is often done using molecular genetics techniques. Once an individual has been diagnosed, the treatment goal is to avoid precipitating episodes that can cause an increased ammonia concentration. The most common treatment combines a low protein diet with nitrogen scavenging agents. Liver transplant is cons ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Urea Cycle
The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts highly toxic ammonia to urea for excretion. This cycle was the first metabolic cycle to be discovered ( Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the TCA cycle. This cycle was described in more detail later on by Ratner and Cohen. The urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys. Function Amino acid catabolism results in waste ammonia. All animals need a way to excrete this product. Most aquatic organisms, or ammonotelic organisms, excrete ammonia without converting it. Organisms that cannot easily and safely remove nitrogen as ammonia convert it to a less toxic substance, such as urea, via the urea cycle, which occurs mainly in the liver. Urea produced by the liver is th ... [...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] |
Autosomal Recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new (''de novo'') or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes ( autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see Sex linkage). Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance such as incomplete d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
