Dopamine Beta Hydroxylase Deficiency
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Dopamine Beta Hydroxylase Deficiency
Dopamine beta (β)-hydroxylase deficiency is a condition involving inadequate dopamine beta-hydroxylase. It is characterized by increased amounts of serum dopamine and the absence of norepinephrine (NE) and epinephrine. Dopamine is released, as a false neurotransmitter, in place of norepinephrine. Other names for norepinephrine include noradrenaline (NA) and noradrenalin. This condition is also sometimes referred to as "norepinephrine deficiency". Researchers of disorders such as schizophrenia are interested in studying this disorder, as patients with these specific diseases can have an increase in the amount of dopamine in their system and yet do not show other symptoms of DβH deficiency. Dopamine beta-hydroxylase deficiency is a very rare form of dysautonomia. It belongs to the class of rare diseases, with "a prevalence of fewer than 20 affected individuals, all of Western European descent", as described in the scientific literature. It is an autosomal recessive disorder cause ...
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Dopamine Beta Hydroxylase
Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine. The three substrates of the enzyme are dopamine, vitamin C (ascorbate), and O2. The products are norepinephrine, dehydroascorbate, and H2O. DBH is a 290 kDa copper-containing oxygenase consisting of four identical subunits, and its activity requires ascorbate as a cofactor. It is the only enzyme involved in the synthesis of small-molecule neurotransmitters that is membrane-bound, making norepinephrine the only known transmitter synthesized inside vesicles. It is expressed in noradrenergic neurons of the central nervous system (i.e. locus coeruleus) and peripheral nervous systems (i.e. sympathetic ganglia), as well as in chromaffin cells of the adrenal medulla. Mechanism of catalysis Based on the observations of what happens when there is no substrate, o ...
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Exercise Intolerance
Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but can result from various disorders. In most cases, the specific reason that exercise is not tolerated is of considerable significance when trying to isolate the cause down to a specific disease. Dysfunctions involving the pulmonary, cardiovascular or neuromuscular systems have been frequently found to be associated with exercise intolerance, with behavioural causes also playing a part. Signs and symptoms Exercise in this context means physical activity, not specifically exercise in a fitness program. For example, a person with exercise intolerance after a heart attack may not be able to sustain the a ...
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Adrenergic Receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example. Many cells have these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system (SNS). The SNS is responsible for the fight-or-flight response, which is triggered by experiences such as exercise or fear-causing situations. This response dilates pupils, increases heart rate, mobilizes energy, and diverts blood flow from non-essential organs to skeletal muscle. These effects together tend to increase physical performance momentarily. History By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different ...
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Phenylpropanolamine
Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to control urinary incontinence in dogs. Chemistry PPA is also known as β-hydroxyamphetamine, and is a member of the phenethylamine and amphetamine chemical classes. It is closely related to the cathinones (β-ketoamphetamines). The compound exists as four stereoisomers, which include ''d''- and ''l''-norephedrine and ''d''- and ''l''-norpseudoephedrine. ''d''-Norpseudoephedrine is also known as cathine, and is found naturally in '' Catha edulis'' (khat). Pharmaceutical drug preparations of PPA have varied in their stereoisomer composition in different countries, which may explain differences in misuse and side effect profiles. Analogues of PPA include ephedrine, pseudoephedrine, amphetamine, methamphetamine, and cathinone. PPA, str ...
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L-DOPA
-DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA, make it via biosynthesis from the amino acid -tyrosine. -DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, -DOPA itself mediates neurotrophic factor release by the brain and CNS. -DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia. -DOPA has a counterpart with opposite chirality, -DOPA. As is true for many molecules, the human body produces only one of these isomers (the -DOPA form). The ...
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Blood–brain Barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the Capillary, capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive transport, passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function. The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and Molecular mass, large or Hydrophile, hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of Hydr ...
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Catecholamine
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a substituent of a larger molecule, where it represents a 1,2-dihydroxybenzene group. Catecholamines are derived from the amino acid tyrosine, which is derived from dietary sources as well as synthesis from phenylalanine. Catecholamines are water-soluble and are 50% bound to plasma proteins in circulation. Included among catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. Release of the hormones epinephrine and norepinephrine from the adrenal medulla of the adrenal glands is part of the fight-or-flight response. Tyrosine is created from phenylalanine by hydroxylation by the enzyme phenylalanine hydroxylase. Tyrosine is also ingested directly from dietary protein. Catecholamine-secreting cells use sev ...
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Droxidopa
Droxidopa (INN; trade name Northera; also known as L-DOPS, L-''threo''-dihydroxyphenylserine, L-''threo''-DOPS and SM-5688) is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine (noradrenaline). Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier (BBB). Medical uses * Neurogenic orthostatic hypotension (NOH) dopamine beta hydrolase deficiency, as well as NOH associated with multiple system atrophy (MSA), familial amyloid polyneuropathy (FAP), pure autonomic failure (PAF). * Intradialytic hypotension (IDH) or hemodialysis-induced hypotension. * Freezing of gait in Parkinson's disease (off-label) Side effects With over 20 years on the market, droxidopa has proven to have few side effects of which most are mild. The most common side effects reported in clinical trials include headache, dizziness, nausea, hypertension and fatigue. Pharmacology Droxidopa is a prodrug of norepinephrine used to incr ...
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Prolactin
Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pituitary gland in response to eating, mating, estrogen treatment, ovulation and nursing. It is secreted heavily in pulses in between these events. Prolactin plays an essential role in metabolism, regulation of the immune system and pancreatic development. Discovered in non-human animals around 1930 by Oscar Riddle and confirmed in humans in 1970 by Henry Friesen, prolactin is a peptide hormone, encoded by the ''PRL'' gene. In mammals, prolactin is associated with milk production; in fish it is thought to be related to the control of water and salt balance. Prolactin also acts in a cytokine-like manner and as an important regulator of the immune system. It has important cell cycle-related functions as a growth-, differentiating- and anti ...
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T Wave
In electrocardiography, the T wave represents the repolarization of the ventricles. The interval from the beginning of the QRS complex to the apex of the T wave is referred to as the ''absolute refractory period''. The last half of the T wave is referred to as the ''relative refractory period'' or ''vulnerable period''. The T wave contains more information than the QT interval. The T wave can be described by its symmetry, skewness, slope of ascending and descending limbs, amplitude and subintervals like the Tpeak–Tend interval. In most leads, the T wave is positive. This is due to the repolarization of the membrane. During ventricle contraction (QRS complex), the heart depolarizes. Repolarization of the ventricle happens in the opposite direction of depolarization and is negative current, signifying the relaxation of the cardiac muscle of the ventricles. But this negative flow causes a positive T wave; although the cell becomes more negatively charged, the net effect is in t ...
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Connective Tissue Disease
A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs. These tissues form a framework, or matrix, for the body, and are composed of two major structural protein molecules: collagen and elastin. There are many different types of collagen protein in each of the body's tissues. Elastin has the capability of stretching and returning to its original length—like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue disease, it is common for collagen and elastin to become injured by inflammation (ICT). Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues ...
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