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37-434: 2166 14073 ENSG00000117480 ENSMUSG00000034171 O00519 O08914 NM_001441 NM_010173 NP_001432 NP_034303 Fatty-acid amide hydrolase 1 ( FAAH ) is a member of the serine hydrolase family of enzymes . It was first shown to break down anandamide (AEA), an N -acylethanolamine (NAE) in 1993. In humans, it is encoded by the gene FAAH . FAAH is an integral membrane hydrolase with

74-474: A delta cis double bond . Insulin medication increases the production and activity of FAAH. The FAAH gene contains a single nucleotide polymorphism (SNP) called rs324420. The variant allele, C385A, is associated with a higher sensitivity of FAAH to proteolytic degradation and a shorter half-life compared to the standard C variant. As a result, carriers of the A variant has increased N -acylethanolamine (NAE) levels and anandamide (AEA) signaling at

111-733: A first-order reaction is given by the following equation: [ A ] 0 / 2 = [ A ] 0 exp ⁡ ( − k t 1 / 2 ) {\displaystyle [{\ce {A}}]_{0}/2=[{\ce {A}}]_{0}\exp(-kt_{1/2})} It can be solved for k t 1 / 2 = − ln ⁡ ( [ A ] 0 / 2 [ A ] 0 ) = − ln ⁡ 1 2 = ln ⁡ 2 {\displaystyle kt_{1/2}=-\ln \left({\frac {[{\ce {A}}]_{0}/2}{[{\ce {A}}]_{0}}}\right)=-\ln {\frac {1}{2}}=\ln 2} For

148-407: A first-order reaction, the half-life of a reactant is independent of its initial concentration. Therefore, if the concentration of A at some arbitrary stage of the reaction is [A] , then it will have fallen to ⁠ 1 / 2 ⁠ [A] after a further interval of ⁠ ln ⁡ 2 k . {\displaystyle {\tfrac {\ln 2}{k}}.} ⁠ Hence,

185-446: A human being is about 9 to 10 days, though this can be altered by behavior and other conditions. The biological half-life of caesium in human beings is between one and four months. The concept of a half-life has also been utilized for pesticides in plants , and certain authors maintain that pesticide risk and impact assessment models rely on and are sensitive to information describing dissipation from plants. In epidemiology ,

222-601: A semispecific FAAH inhibitor. By controlling the levels of FAAH activity, they modulate endogenous N -acylethanolamine levels. In the Enzyme Commission numbering scheme, "fatty acid amide hydrolase" is EC 3.5.1.99 . The number applies to all enzymes that have the chemical activity; in humans it covers both the genes FAAH and FAAH2 . The systematic name is "fatty acylamide amidohydrolase". Recorded synonyms include "oleamide hydrolase", "anandamide amidohydrolase". Serine hydrolase Serine hydrolases are one of

259-569: A single N -terminal transmembrane domain . In vitro, FAAH has esterase and amidase activity. In vivo, FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of the FAAs include: FAAH knockout mice display highly elevated (>15-fold) levels of N -acylethanolamines and N -acyltaurines in various tissues. Because of their significantly elevated anandamide levels, FAAH KOs have an analgesic phenotype, showing reduced pain sensation in

296-946: A statistical computer program . An exponential decay can be described by any of the following four equivalent formulas: N ( t ) = N 0 ( 1 2 ) t t 1 / 2 N ( t ) = N 0 2 − t t 1 / 2 N ( t ) = N 0 e − t τ N ( t ) = N 0 e − λ t {\displaystyle {\begin{aligned}N(t)&=N_{0}\left({\frac {1}{2}}\right)^{\frac {t}{t_{1/2}}}\\N(t)&=N_{0}2^{-{\frac {t}{t_{1/2}}}}\\N(t)&=N_{0}e^{-{\frac {t}{\tau }}}\\N(t)&=N_{0}e^{-\lambda t}\end{aligned}}} where The three parameters t ½ , τ , and λ are directly related in

333-516: A strong correlation between national percentage of very happy people (as measured by the World Values Survey ) and the presence of the rs324420 C385A allele in citizens' genetic make-up. The C385A allele was initially provisionally linked to drug abuse and dependence but this was not borne out in subsequent studies. According to later studies, carriers of the A allele are more likely to try cannabis, but less likely to become dependent. FAAH-OUT

370-417: A substance can be complex, due to factors including accumulation in tissues , active metabolites , and receptor interactions. While a radioactive isotope decays almost perfectly according to first order kinetics, where the rate constant is a fixed number, the elimination of a substance from a living organism usually follows more complex chemical kinetics. For example, the biological half-life of water in

407-413: A useful strategy to treat anxiety disorders , as inhibition produce analgesic , anxiolytic , neuroprotective , and anti-inflammatory effects by elevated N -acylethanolamines (NAE's) and their activation of cannabinoid receptors . Activation of the cannabinoid receptor CB1 or CB2 in different tissues , including skin , inhibit FAAH, and thereby increases endocannabinoid levels. Based on

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444-704: Is a pseudogene downstream of the FAAH coding region. It expresses a long non-coding RNA (lncRNA) that increases the expression of FAAH. In 2019, a Scottish woman named Jo Cameron was found to have both a previously unreported microdeletion mutation in FAAH-OUT and a rs324420 C385A mutation. The result is extreme disruption of FAAH function leading to elevated anandamide levels. She was immune to anxiety, unable to experience fear, and insensitive to pain. The frequent burns and cuts suffered due to her hypoalgesia healed quicker than average with little or no scarring. Her son, who shares

481-399: Is a half-life describing any exponential-decay process. For example: The term "half-life" is almost exclusively used for decay processes that are exponential (such as radioactive decay or the other examples above), or approximately exponential (such as biological half-life discussed below). In a decay process that is not even close to exponential, the half-life will change dramatically while

518-457: Is proportional to the square of the concentration. By integrating this rate, it can be shown that the concentration [A] of the reactant decreases following this formula: 1 [ A ] = k t + 1 [ A ] 0 {\displaystyle {\frac {1}{[{\ce {A}}]}}=kt+{\frac {1}{[{\ce {A}}]_{0}}}} We replace [A] for ⁠ 1 / 2 ⁠ [A] 0 in order to calculate

555-421: Is the time it takes for a substance (drug, radioactive nuclide, or other) to lose one-half of its pharmacologic, physiologic, or radiological activity. In a medical context, the half-life may also describe the time that it takes for the concentration of a substance in blood plasma to reach one-half of its steady-state value (the "plasma half-life"). The relationship between the biological and plasma half-lives of

592-458: The FAAH-OUT deletion but has no C385A mutation, has a lesser degree of pain insensitivity. A 2023 study looks further into the functions of FAAH-OUT using transcriptomic analyses of cell models, some created anew using CRISPR-Cas9, others obtained from the 2019 patient. The study confirms that FAAH-OUT increases the expression of FAAH, both via its lncRNA product and through an intronic enhancer called FAAH-AMP. Loss of FAAH-OUT also changes

629-450: The cannabinoid receptors . The A variant may be responsible for lower levels of the FAAH protein seen in high-performing athletes, providing increased physical and mental fitness. However, among elite Polish athletes, the A variant is under-represented regardless of metabolic characteristics of their sport disciplines; this seems to suggest an opposite role for the A variant. A 2017 study found

666-475: The hot plate test , the formalin test , and the tail flick test . Finally, because of their impaired ability to degrade anandamide, FAAH KOs also display supersensitivity to exogenous anandamide, a cannabinoid receptor (CB) agonist. Due to the ability of FAAH to regulate nociception , it is currently viewed as an attractive drug target for the treatment of pain. Studies in cells and animals and genetic studies in humans have shown that inhibiting FAAH may be

703-417: The analogous formula is: 1 T 1 / 2 = 1 t 1 + 1 t 2 + 1 t 3 + ⋯ {\displaystyle {\frac {1}{T_{1/2}}}={\frac {1}{t_{1}}}+{\frac {1}{t_{2}}}+{\frac {1}{t_{3}}}+\cdots } For a proof of these formulas, see Exponential decay § Decay by two or more processes . There

740-409: The atoms remaining, only approximately , because of the random variation in the process. Nevertheless, when there are many identical atoms decaying (right boxes), the law of large numbers suggests that it is a very good approximation to say that half of the atoms remain after one half-life. Various simple exercises can demonstrate probabilistic decay, for example involving flipping coins or running

777-418: The decay is happening. In this situation it is generally uncommon to talk about half-life in the first place, but sometimes people will describe the decay in terms of its "first half-life", "second half-life", etc., where the first half-life is defined as the time required for decay from the initial value to 50%, the second half-life is from 50% to 25%, and so on. A biological half-life or elimination half-life

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814-429: The expression of a wide network of genes beyond FAAH itself. For example, although the pain insensitivity is mostly due to loss of FAAH function (via increased endocannabinoid levels and reduced ACKR3 expression), lack of depression and anxiety is instead due to a non-canonical Wnt pathway upregulating BDNF . The increased wound healing is due to both pathways: loss of FAAH function increases N -acyltaurine levels;

851-462: The following way: t 1 / 2 = ln ⁡ ( 2 ) λ = τ ln ⁡ ( 2 ) {\displaystyle t_{1/2}={\frac {\ln(2)}{\lambda }}=\tau \ln(2)} where ln(2) is the natural logarithm of 2 (approximately 0.693). In chemical kinetics , the value of the half-life depends on the reaction order : The rate of this kind of reaction does not depend on

888-411: The half-life is defined in terms of probability : "Half-life is the time required for exactly half of the entities to decay on average ". In other words, the probability of a radioactive atom decaying within its half-life is 50%. For example, the accompanying image is a simulation of many identical atoms undergoing radioactive decay. Note that after one half-life there are not exactly one-half of

925-403: The half-life of a first order reaction is given as the following: t 1 / 2 = ln ⁡ 2 k {\displaystyle t_{1/2}={\frac {\ln 2}{k}}} The half-life of a first order reaction is independent of its initial concentration and depends solely on the reaction rate constant, k . In second order reactions, the rate of reaction

962-602: The half-life of second order reactions depends on the initial concentration and rate constant . Some quantities decay by two exponential-decay processes simultaneously. In this case, the actual half-life T ½ can be related to the half-lives t 1 and t 2 that the quantity would have if each of the decay processes acted in isolation: 1 T 1 / 2 = 1 t 1 + 1 t 2 {\displaystyle {\frac {1}{T_{1/2}}}={\frac {1}{t_{1}}}+{\frac {1}{t_{2}}}} For three or more processes,

999-533: The half-life of the reactant A 1 [ A ] 0 / 2 = k t 1 / 2 + 1 [ A ] 0 {\displaystyle {\frac {1}{[{\ce {A}}]_{0}/2}}=kt_{1/2}+{\frac {1}{[{\ce {A}}]_{0}}}} and isolate the time of the half-life ( t ½ ): t 1 / 2 = 1 [ A ] 0 k {\displaystyle t_{1/2}={\frac {1}{[{\ce {A}}]_{0}k}}} This shows that

1036-415: The hydrolytic mechanism of fatty acid amide hydrolase, a large number of irreversible and reversible inhibitors of this enzyme have been developed. Some of the more significant compounds are listed below; Structural and conformational properties that contribute to enzyme inhibition and substrate binding imply an extended bound conformation, and a role for the presence, position, and stereochemistry of

1073-414: The largest known enzyme classes comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A defining characteristic of these enzymes is the presence of a particular serine at the active site , which is used for the hydrolysis of substrates . The hydrolysis of the ester or peptide bond proceeds in two steps. First, the acyl part of the substrate (the acid part of an ester or

1110-528: The non-canonical Wnt pathway is also beneficial to healing. The enzyme is typically assayed making use of a radiolabelled anandamide substrate , which generates free labelled ethanolamine , although alternative LC-MS methods have also been described. The first crystal structure of FAAH was published in 2002 ( PDB code 1MT5). Structures of FAAH with drug-like ligands were first reported in 2008, and include non-covalent inhibitor complexes and covalent adducts. The slime mold Dictyostelium discoideum produces

1147-433: The part of a peptide ending in a carboxyl group) is transferred to the serine, making a new ester or amide bond and releasing the other part of the substrate (the alcohol of an ester or the part of the peptide ending in an amino group) is released. Later, in a slower step, the bond between the serine and the acyl group is hydrolyzed by water or hydroxide ion, regenerating free enzyme. Unlike other, non-catalytic, serines,

Fatty-acid amide hydrolase 1 - Misplaced Pages Continue

1184-422: The principle in 1907, was shortened to half-life in the early 1950s. Rutherford applied the principle of a radioactive element's half-life in studies of age determination of rocks by measuring the decay period of radium to lead-206 . Half-life is constant over the lifetime of an exponentially decaying quantity, and it is a characteristic unit for the exponential decay equation. The accompanying table shows

1221-459: The reactant. Thus the concentration will decrease exponentially. [ A ] = [ A ] 0 exp ⁡ ( − k t ) {\displaystyle [{\ce {A}}]=[{\ce {A}}]_{0}\exp(-kt)} as time progresses until it reaches zero, and the half-life will be constant, independent of concentration. The time t ½ for [A] to decrease from [A] 0 to ⁠ 1 / 2 ⁠ [A] 0 in

1258-432: The reactive serine of these hydrolases is typically activated by a proton relay involving a catalytic triad consisting of the serine, an acidic residue (e.g. aspartate or glutamate ) and a basic residue (usually histidine ), although variations on this mechanism exist. Superfamilies of serine hydrolases includes: Half-life The original term, half-life period , dating to Ernest Rutherford 's discovery of

1295-465: The reduction of a quantity as a function of the number of half-lives elapsed. A half-life often describes the decay of discrete entities, such as radioactive atoms. In that case, it does not work to use the definition that states "half-life is the time required for exactly half of the entities to decay". For example, if there is just one radioactive atom, and its half-life is one second, there will not be "half of an atom" left after one second. Instead,

1332-575: The substrate concentration , [A] . Thus the concentration decreases linearly. [ A ] = [ A ] 0 − k t {\displaystyle [{\ce {A}}]=[{\ce {A}}]_{0}-kt} In order to find the half-life, we have to replace the concentration value for the initial concentration divided by 2: [ A ] 0 / 2 = [ A ] 0 − k t 1 / 2 {\displaystyle [{\ce {A}}]_{0}/2=[{\ce {A}}]_{0}-kt_{1/2}} and isolate

1369-412: The time: t 1 / 2 = [ A ] 0 2 k {\displaystyle t_{1/2}={\frac {[{\ce {A}}]_{0}}{2k}}} This t ½ formula indicates that the half-life for a zero order reaction depends on the initial concentration and the rate constant. In first order reactions, the rate of reaction will be proportional to the concentration of

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