Corticosteroid 11-beta-dehydrogenase Isozyme 2
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Corticosteroid 11-beta-dehydrogenase Isozyme 2
Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the gene. Function Corticosteroid 11-β-dehydrogenase isozyme 2 is an NAD+-dependent enzyme expressed in aldosterone-selective epithelial tissues such as the kidney, colon, salivary and sweat glands. HSD211B2 expression is also found in the brainstem in a small, aldosterone-sensitive subset of neurons located in the nucleus of the solitary tract referred to as HSD2 neurons. In these tissues, HSD11B2 oxidizes the glucocorticoid cortisol to the inactive metabolite cortisone, thus preventing illicit activation of the mineralocorticoid receptor. This protective mechanism is necessary because cortisol circulates at 100- to 1000-fold higher concentrations than aldosterone, and binds with equal affinity to the mineralocorticoid receptor, thereby out-competing aldosterone in cells that do not produce HSD11B2. This glucocorticoid-inactivating enzyme ...
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Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels. It does so primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron. It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume.Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14 When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease. Aldosterone has exactly the opposite function of the atrial natriure ...
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Brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is continuous with the thalamus of the diencephalon through the tentorial notch, and sometimes the diencephalon is included in the brainstem. The brainstem is very small, making up around only 2.6 percent of the brain's total weight. It has the critical roles of regulating cardiac, and respiratory function, helping to control heart rate and breathing rate. It also provides the main motor and sensory nerve supply to the face and neck via the cranial nerves. Ten pairs of cranial nerves come from the brainstem. Other roles include the regulation of the central nervous system and the body's sleep cycle. It is also of prime importance in the conveyance of motor and sensory pathways from the rest of the brain to the body, and from the body back to t ...
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Nucleus Of The Solitary Tract
In the human brainstem, the solitary nucleus, also called nucleus of the solitary tract, nucleus solitarius, and nucleus tractus solitarii, (SN or NTS) is a series of purely sensory nuclei (clusters of nerve cell bodies) forming a vertical column of grey matter embedded in the medulla oblongata. Through the center of the SN runs the solitary tract, a white bundle of nerve fibers, including fibers from the facial, glossopharyngeal and vagus nerves, that innervate the SN. The SN projects to, among other regions, the reticular formation, parasympathetic preganglionic neurons, hypothalamus and thalamus, forming circuits that contribute to autonomic regulation. Cells along the length of the SN are arranged roughly in accordance with function; for instance, cells involved in taste are located in the rostral part, while those receiving information from cardio-respiratory and gastrointestinal processes are found in the caudal part. Inputs * Taste information from the facial nerve via the ...
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HSD2 Neurons
HSD2 neurons are a small group of neurons in the brainstem which are uniquely sensitive to the mineralocorticosteroid hormone aldosterone, through expression of HSD11B2. They are located within the caudal medulla oblongata, in the nucleus of the solitary tract (NTS). HSD2 neurons are activated during a prolonged deficit in body sodium or fluid volume, as occurs after dietary sodium deprivation or during frank hypovolemia. They are also activated by supraphysiologic stimulation of the mineralocorticoid receptor. They are inactivated when salt is ingested. To date, HSD2 neurons have been identified and studied only in rats and mice. Basic characteristics The term "HSD2 neurons" is used in the scientific literature to refer to a subpopulation of neurons in the NTS which express both the mineralocorticoid receptor (MR) and 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2). HSD2 is an enzyme that metabolizes cortisol and other glucocorticosteroids, which typically prevent ...
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Cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland. It is produced in other tissues in lower quantities. It is released with a diurnal cycle and its release is increased in response to stress and low blood-glucose concentration. It functions to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. It also decreases bone formation. Many of these functions are carried out by cortisol binding to glucocorticoid or mineralocorticoid receptors inside the cell, which then bind to DNA to impact gene expression. Health effects Metabolic response Metabolism of glucose In general, cortisol stimulates gluconeogenesis (the synthesis of 'new' glucose from non-carbohydrate sources, which occurs mainly in th ...
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Cortisone
Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase isozyme 2 into the inactive metabolite cortisone, particularly in the kidneys. Cortisone is converted back to the active steroid cortisol by the action of the enzyme 11β-Hydroxysteroid dehydrogenase type 1, particularly in the liver. The term "cortisone" is frequently misused to mean either any corticosteroid or hydrocortisone, which is actually another name for cortisol. Many who speak of receiving a "cortisone shot" or taking "cortisone" are actually receiving hydrocortisone or one of many other, much more potent synthetic corticosteroids; it is unlikely that the drug administered is actually cortisone. Cortisone can be administered as a prodrug, meaning it has to be converted by the body (speci ...
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Mineralocorticoid Receptor
The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31.1-31.2. MR is a receptor with equal affinity for mineralocorticoids and glucocorticoids. It belongs to the nuclear receptor family where the ligand diffuses into cells, interacts with the receptor and results in a signal transduction affecting specific gene expression in the nucleus. The selective responsive of some tissues and organs to mineralocorticoids over glucocorticoids occurs because mineralocorticoid-responsive cells express Corticosteroid 11-beta-dehydrogenase isozyme 2, an enzyme which selectively inactivates glucocorticoids more readily than mineralocorticoids. Function MR is expressed in many tissues, such as the kidney, colon, heart, central nervous system (hippocampus), brown adipose tissue and sweat glands. In epith ...
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Granule Cells
A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granule, a structure characteristic of the azurophil eukaryotic cell type ** Chromaffin granule, a structure characteristic of the chromophil eukaryotic cell type. * Astrophysics and geology: ** Granule (solar physics), a visible structure in the photosphere of the Sun arising from activity in the Sun's convective zone ** Martian spherules, spherical granules of material found on the surface of the planet Mars ** Granule (geology), a specified particle size of 2–4 millimetres (-1 to -2 on the φ scale) * Granule, in pharmaceutical terms, small particles gathered into a larger, permanent aggregate in which the original particles can still be identified * Granule (Oracle DBMS), a unit of contiguously allocated virtual memory * Granular synthesis ...
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Glycyrrhizin
Glycyrrhizin (or glycyrrhizic acid or glycyrrhizinic acid) is the chief sweet-tasting constituent of ''Glycyrrhiza glabra'' ( liquorice) root. Structurally, it is a saponin used as an emulsifier and gel-forming agent in foodstuffs and cosmetics. Its aglycone is enoxolone. Pharmacokinetics After oral ingestion, glycyrrhizin is hydrolysed to 18β-glycyrrhetinic acid (enoxolone) by intestinal bacteria. After absorption from the gut, 18β-glycyrrhetinic acid is metabolised to 3β-monoglucuronyl-18β-glycyrrhetinic acid in the liver. This metabolite circulates in the bloodstream. Consequently, its oral bioavailability is poor. Most of it is eliminated by bile and only a minor part (0.31–0.67%) by urine. After oral ingestion of 600 mg of glycyrrhizin the metabolite appeared in urine after 1.5 to 14 hours. Maximal concentrations (0.49 to 2.69 mg/L) were achieved after 1.5 to 39 hours and metabolite can be detected in the urine after 2 to 4 days. Flavouring properties Glycyrrhi ...
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Pseudohyperaldosteronism
Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure (hypertension), low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders (e.g. Apparent mineralocorticoid excess syndrome, Liddle's syndrome, and types of Congenital adrenal hyperplasia), acquired conditions (e.g. Cushing's syndrome and mineralocorticoid-producing adrenal tumors), metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific root cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldo ...
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