Biological Pathway: Reactome:R-HSA-5579015
Defective CYP26B1 causes RHFCA related metabolites
find 9 related metabolites which is associated with the biological pathway Defective CYP26B1 causes RHFCA
this pathway object is a organism specific pathway, which is related to taxonomy Homo sapiens (human).
Retinoic acid (RA) is a biologically active analogue of vitamin A (retinol). RA plays an important role in regulating cell growth and differentiation.CYP26A1 and B1 are involved in the metabolic breakdown of RA by 4-hydroxylation. High expression levels of CYP26B1 in the cerebellum and pons of human brain suggests a protective role of specific tissues against retinoid damage (White et al. 2000). Defects in CYP26B1 can cause radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA; MIM:614416), a disease characterised by craniofacial malformations and multiple skeletal anomalies (Laue et al. 2011).
all-trans-Retinoic acid
all-trans-Retinoic acid is an isomer of retinoic acid, the oxidized form of vitamin A. Retinoic acid functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately controls anterior/posterior patterning in early developmental stages (PMID:17495912). It is an important regulator of gene expression during growth and development, and in neoplasms. As a drug, all-trans-retinoic acid is known as tretinoin. Tretinoin is derived from maternal vitamin A and is essential for normal growth and embryonic development. An excess of tretinoin can be teratogenic. Tretinoin is used in the treatment of psoriasis, acne vulgaris, and several other skin diseases. It has also been approved for use in promyelocytic leukemia (leukemia, promyelocytic, acute). Retinoic acid is the oxidized form of Vitamin A. It functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately controls anterior/posterior patterning in early developmental stages (PMID: 17495912). It is an important regulator of gene expression during growth and development, and in neoplasms. Tretinoin, also known as retinoic acid and derived from maternal vitamin A, is essential for normal growth and embryonic development. An excess of tretinoin can be teratogenic. It is used in the treatment of psoriasis; acne vulgaris; and several other skin diseases. It has also been approved for use in promyelocytic leukemia (leukemia, promyelocytic, acute). [HMDB] L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01X - Other antineoplastic agents > L01XF - Retinoids for cancer treatment D - Dermatologicals > D10 - Anti-acne preparations > D10A - Anti-acne preparations for topical use > D10AD - Retinoids for topical use in acne C274 - Antineoplastic Agent > C2122 - Cell Differentiating Agent > C1934 - Differentiation Inducer C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C804 - Retinoic Acid Agent Acquisition and generation of the data is financially supported in part by CREST/JST. C308 - Immunotherapeutic Agent > C129820 - Antineoplastic Immunomodulating Agent D020011 - Protective Agents > D000975 - Antioxidants > D002338 - Carotenoids D003879 - Dermatologic Agents > D007641 - Keratolytic Agents D000970 - Antineoplastic Agents Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha.
Nicotinamide adenine dinucleotide phosphate
NADPH is the reduced form of NADP+, and NADP+ is the oxidized form of NADPH. Nicotinamide adenine dinucleotide phosphate (NADP) is a coenzyme composed of ribosylnicotinamide 5-phosphate (NMN) coupled with a pyrophosphate linkage to 5-phosphate adenosine 2,5-bisphosphate. NADP serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). NADP is formed through the addition of a phosphate group to the 2 position of the adenosyl nucleotide through an ester linkage (Dorland, 27th ed). This extra phosphate is added by the enzyme NAD+ kinase and removed via NADP+ phosphatase. NADP is also known as TPN (triphosphopyridine nucleotide) and it is an important cofactor used in anabolic reactions in all forms of cellular life. Examples include the Calvin cycle, cholesterol synthesis, fatty acid elongation, and nucleic acid synthesis (Wikipedia). Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5-phosphate (NMN) coupled by pyrophosphate linkage to the 5-phosphate adenosine 2,5-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed.) [HMDB]. NADPH is found in many foods, some of which are american pokeweed, rice, ginseng, and ostrich fern. COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS
Oxygen
Oxygen is the third most abundant element in the universe after hydrogen and helium and the most abundant element by mass in the Earths crust. Diatomic oxygen gas constitutes 20.9\\% of the volume of air. All major classes of structural molecules in living organisms, such as proteins, carbohydrates, and fats, contain oxygen, as do the major inorganic compounds that comprise animal shells, teeth, and bone. Oxygen in the form of O2 is produced from water by cyanobacteria, algae and plants during photosynthesis and is used in cellular respiration for all living organisms. Green algae and cyanobacteria in marine environments provide about 70\\% of the free oxygen produced on earth and the rest is produced by terrestrial plants. Oxygen is used in mitochondria to help generate adenosine triphosphate (ATP) during oxidative phosphorylation. For animals, a constant supply of oxygen is indispensable for cardiac viability and function. To meet this demand, an adult human, at rest, inhales 1.8 to 2.4 grams of oxygen per minute. This amounts to more than 6 billion tonnes of oxygen inhaled by humanity per year. At a resting pulse rate, the heart consumes approximately 8-15 ml O2/min/100 g tissue. This is significantly more than that consumed by the brain (approximately 3 ml O2/min/100 g tissue) and can increase to more than 70 ml O2/min/100 g myocardial tissue during vigorous exercise. As a general rule, mammalian heart muscle cannot produce enough energy under anaerobic conditions to maintain essential cellular processes; thus, a constant supply of oxygen is indispensable to sustain cardiac function and viability. However, the role of oxygen and oxygen-associated processes in living systems is complex, and they and can be either beneficial or contribute to cardiac dysfunction and death (through reactive oxygen species). Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that are produced in mammalian cells under normal and pathologic conditions. Many ROS, such as the superoxide anion (O2-)and hydrogen peroxide (H2O2), act within blood vessels, altering mechanisms mediating mechanical signal transduction and autoregulation of cerebral blood flow. Reactive oxygen species are believed to be involved in cellular signaling in blood vessels in both normal and pathologic states. The major pathway for the production of ROS is by way of the one-electron reduction of molecular oxygen to form an oxygen radical, the superoxide anion (O2-). Within the vasculature there are several enzymatic sources of O2-, including xanthine oxidase, the mitochondrial electron transport chain, and nitric oxide (NO) synthases. Studies in recent years, however, suggest that the major contributor to O2- levels in vascular cells is the membrane-bound enzyme NADPH-oxidase. Produced O2- can react with other radicals, such as NO, or spontaneously dismutate to produce hydrogen peroxide (H2O2). In cells, the latter reaction is an important pathway for normal O2- breakdown and is usually catalyzed by the enzyme superoxide dismutase (SOD). Once formed, H2O2 can undergo various reactions, both enzymatic and nonenzymatic. The antioxidant enzymes catalase and glutathione peroxidase act to limit ROS accumulation within cells by breaking down H2O2 to H2O. Metabolism of H2O2 can also produce other, more damaging ROS. For example, the endogenous enzyme myeloperoxidase uses H2O2 as a substrate to form the highly reactive compound hypochlorous acid. Alternatively, H2O2 can undergo Fenton or Haber-Weiss chemistry, reacting with Fe2+/Fe3+ ions to form toxic hydroxyl radicals (-.OH). (PMID: 17027622, 15765131) [HMDB]. Oxygen is found in many foods, some of which are soy bean, watermelon, sweet basil, and spinach. Oxygen is the third most abundant element in the universe after hydrogen and helium and the most abundant element by mass in the Earths crust. Diatomic oxygen gas constitutes 20.9\\% of the volume of air. All major classes of structural molecules in living organisms, such as proteins, carbohydrates, and fats, contain oxygen, as do the major inorganic compounds that comprise animal shells, teeth, and bone. Oxygen in the form of O2 is produced from water by cyanobacteria, algae and plants during photosynthesis and is used in cellular respiration for all living organisms. Green algae and cyanobacteria in marine environments provide about 70\\% of the free oxygen produced on earth and the rest is produced by terrestrial plants. Oxygen is used in mitochondria to help generate adenosine triphosphate (ATP) during oxidative phosphorylation. For animals, a constant supply of oxygen is indispensable for cardiac viability and function. To meet this demand, an adult human, at rest, inhales 1.8 to 2.4 grams of oxygen per minute. This amounts to more than 6 billion tonnes of oxygen inhaled by humanity per year. At a resting pulse rate, the heart consumes approximately 8-15 ml O2/min/100 g tissue. This is significantly more than that consumed by the brain (approximately 3 ml O2/min/100 g tissue) and can increase to more than 70 ml O2/min/100 g myocardial tissue during vigorous exercise. As a general rule, mammalian heart muscle cannot produce enough energy under anaerobic conditions to maintain essential cellular processes; thus, a constant supply of oxygen is indispensable to sustain cardiac function and viability. However, the role of oxygen and oxygen-associated processes in living systems is complex, and they and can be either beneficial or contribute to cardiac dysfunction and death (through reactive oxygen species). Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that are produced in mammalian cells under normal and pathologic conditions. Many ROS, such as the superoxide anion (O2-)and hydrogen peroxide (H2O2), act within blood vessels, altering mechanisms mediating mechanical signal transduction and autoregulation of cerebral blood flow. Reactive oxygen species are believed to be involved in cellular signaling in blood vessels in both normal and pathologic states. The major pathway for the production of ROS is by way of the one-electron reduction of molecular oxygen to form an oxygen radical, the superoxide anion (O2-). Within the vasculature there are several enzymatic sources of O2-, including xanthine oxidase, the mitochondrial electron transport chain, and nitric oxide (NO) synthases. Studies in recent years, however, suggest that the major contributor to O2- levels in vascular cells is the membrane-bound enzyme NADPH-oxidase. Produced O2- can react with other radicals, such as NO, or spontaneously dismutate to produce hydrogen peroxide (H2O2). In cells, the latter reaction is an important pathway for normal O2- breakdown and is usually catalyzed by the enzyme superoxide dismutase (SOD). Once formed, H2O2 can undergo various reactions, both enzymatic and nonenzymatic. The antioxidant enzymes catalase and glutathione peroxidase act to limit ROS accumulation within cells by breaking down H2O2 to H2O. Metabolism of H2O2 can also produce other, more damaging ROS. For example, the endogenous enzyme myeloperoxidase uses H2O2 as a substrate to form the highly reactive compound hypochlorous acid. Alternatively, H2O2 can undergo Fenton or Haber-Weiss chemistry, reacting with Fe2+/Fe3+ ions to form toxic hydroxyl radicals (-.OH). (PMID: 17027622, 15765131). V - Various > V03 - All other therapeutic products > V03A - All other therapeutic products > V03AN - Medical gases
Hydrogen Ion
Hydrogen ion, also known as proton or h+, is a member of the class of compounds known as other non-metal hydrides. Other non-metal hydrides are inorganic compounds in which the heaviest atom bonded to a hydrogen atom is belongs to the class of other non-metals. Hydrogen ion can be found in a number of food items such as lowbush blueberry, groundcherry, parsley, and tarragon, which makes hydrogen ion a potential biomarker for the consumption of these food products. Hydrogen ion exists in all living organisms, ranging from bacteria to humans. In humans, hydrogen ion is involved in several metabolic pathways, some of which include cardiolipin biosynthesis cl(i-13:0/a-25:0/a-21:0/i-15:0), cardiolipin biosynthesis cl(a-13:0/a-17:0/i-13:0/a-25:0), cardiolipin biosynthesis cl(i-12:0/i-13:0/a-17:0/a-15:0), and cardiolipin biosynthesis CL(16:1(9Z)/22:5(4Z,7Z,10Z,13Z,16Z)/18:1(11Z)/22:5(7Z,10Z,13Z,16Z,19Z)). Hydrogen ion is also involved in several metabolic disorders, some of which include de novo triacylglycerol biosynthesis TG(20:3(8Z,11Z,14Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z)/22:5(7Z,10Z,13Z,16Z,19Z)), de novo triacylglycerol biosynthesis TG(18:2(9Z,12Z)/20:0/20:4(5Z,8Z,11Z,14Z)), de novo triacylglycerol biosynthesis TG(18:4(6Z,9Z,12Z,15Z)/18:3(9Z,12Z,15Z)/18:4(6Z,9Z,12Z,15Z)), and de novo triacylglycerol biosynthesis TG(24:0/20:5(5Z,8Z,11Z,14Z,17Z)/24:0). A hydrogen ion is created when a hydrogen atom loses or gains an electron. A positively charged hydrogen ion (or proton) can readily combine with other particles and therefore is only seen isolated when it is in a gaseous state or a nearly particle-free space. Due to its extremely high charge density of approximately 2×1010 times that of a sodium ion, the bare hydrogen ion cannot exist freely in solution as it readily hydrates, i.e., bonds quickly. The hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes. Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions . Hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes. Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions. Under aqueous conditions found in biochemistry, hydrogen ions exist as the hydrated form hydronium, H3O+, but these are often still referred to as hydrogen ions or even protons by biochemists. [Wikipedia])
9,13-cis-Retinoic acid
9,13-cis-Retinoic acid belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof. Retinoids (vitamin A and its analogs) are essential dietary substances that are needed by mammals for reproduction, normal embryogenesis, growth, vision, and maintaining normal cellular differentiation and the integrity of the immune system. Within cells, retinoids regulate gene transcription acting through ligand-dependent transcription factors, the retinoic acid receptors (RARs), and the retinoid X receptors (RXRs). Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL). [HMDB] L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01X - Other antineoplastic agents > L01XF - Retinoids for cancer treatment D - Dermatologicals > D10 - Anti-acne preparations > D10A - Anti-acne preparations for topical use > D10AD - Retinoids for topical use in acne C274 - Antineoplastic Agent > C2122 - Cell Differentiating Agent > C1934 - Differentiation Inducer C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C804 - Retinoic Acid Agent C308 - Immunotherapeutic Agent > C129820 - Antineoplastic Immunomodulating Agent D020011 - Protective Agents > D000975 - Antioxidants > D002338 - Carotenoids D003879 - Dermatologic Agents > D007641 - Keratolytic Agents D000970 - Antineoplastic Agents Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha.
Tretinoin
L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01X - Other antineoplastic agents > L01XF - Retinoids for cancer treatment D - Dermatologicals > D10 - Anti-acne preparations > D10A - Anti-acne preparations for topical use > D10AD - Retinoids for topical use in acne C274 - Antineoplastic Agent > C2122 - Cell Differentiating Agent > C1934 - Differentiation Inducer C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C804 - Retinoic Acid Agent C308 - Immunotherapeutic Agent > C129820 - Antineoplastic Immunomodulating Agent D020011 - Protective Agents > D000975 - Antioxidants > D002338 - Carotenoids D003879 - Dermatologic Agents > D007641 - Keratolytic Agents D000970 - Antineoplastic Agents CONFIDENCE standard compound; INTERNAL_ID 135 relative retention time with respect to 9-anthracene Carboxylic Acid is 1.574 Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha.
NADPH
The reduced form of NADP+; used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent. COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS