CAMP is an important second messenger of cell signal transduction.After the receptor on the cell membrane combines with the ligand, it activates G protein, and then activatesAdenylate cyclaseIt catalyzes ATP to generate cyclic adenosine monophosphate and has a wide range of physiological functions.When the cell is stimulated by the outside world, the extracellular signal molecule first combines with the receptor to form a complex, and then activates the Gs protein on the cell membrane. The activated Gs protein reactivates the adenylate cyclase (AC) on the cell membrane, catalyzing ATP to remove a pyrophosphate and generate cAMP.The generated cAMP acts as the second messenger to phosphorylate the target cell protein by activating APK (cAMP dependent protein kinase), thus regulating the cell response, and cAMP is finallyphosphodiesterase(PDE) is hydrolyzed to AMP and inactivated.CAMP generation and decomposition process dependencies exist.[1]
Chinese name
Cyclic adenylate
Foreign name
cyclic adenosine monophosphate
Full name
Adenosine - 3 ', 5' - cyclic monophosphate
Abbreviation
cAMP
Location
It exists in animal and plant cells and microorganisms
In trace amountsplant cellAnd microorganisms.When multiple hormones in the body act on cells, they can promote cells to produce this substance, which in turn regulates the physiological activities and material metabolism of cells.
The reason why cAMP is called the second messenger in the cell is that some hormones or other moleculesSignal stimulusactivationAdenylate cyclaseIt catalyzes the cyclization of ATP.
Generation and decomposition
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When the cell is stimulated by the outside world, the extracellular signal molecule first combines with the receptor to form a complex, and then activates the Gs protein on the cell membrane. The activated Gs protein reactivates the adenylate cyclase (AC) on the cell membrane, catalyzing ATP to remove a pyrophosphate and generate cAMP.The generated cAMP acts as the H messenger by activating APK (cAMP dependencyprotein kinase）, phosphorylate the target cell protein to regulate the cell reaction, and cAMP is finallyphosphodiesterase(PDE) is hydrolyzed to 5 '- AMP and inactivated.The formation and decomposition of cAMP depend on the presence of Mg2+.AC and PDE can regulate the concentration of cAMP in cells from two different aspects, thus affecting the functions of cells, tissues and organs.When AC activity increased, cAMP concentration increased, and when PDE concentration increased, cAMP concentration decreased.The regulation of cAMP by PDE depends not only on the activation and inhibition of PDE, but also on the composition and subcellular distribution of PDE in cells.
Content and distribution of cAMP in animals
Since Sutherland first discovered CAMP in liver homogenate in 1957, people have successively found cAMP in many tissues or body fluids, such as kidney, lung, intestine, coronary artery, bronchus, pituitary, platelets, milk, testis, bone marrow, etc.In mammals, cAMP is distributed in all tissues except red blood cells. Under normal conditions, the concentration of cAMP in cells is 0.1~l μ M, but it can rise to more than 100 times under the effect of hormone or stress.The concentration of CAMP in plasma is lower than that in cells, about 10 nMo cAMP in cells can be released into blood, indicating that the changes in plasma CAMP can reflect the physiological changes of body organs to a certain extent.
Regulation of cAMP on cell metabolism CAMP regulates many metabolic processes of cells by regulating enzyme activity.In the presence of ATP, PKA can activate the activities of many key metabolic enzymes in cells (such as lipase) or inhibit the activities of some enzymes (such as active glycogen synthase I), eventually leading to the acceleration or inhibition of some metabolic reactions (Yi Jianhua, 1981).Krebs et al. studied the regulation of cAMP on glycogen synthesis and glycogen decomposition enzymes in 1962.adrenalineandGlucagonSuch hormones can increase CAMP level, activate PKA, PKA and then activate glycogen phosphorylation kinaseGlycogen phosphorylasePhosphorylation, so that the glycogen phosphorylase changes from the inactive b form to the active a form, which catalyzes the decomposition of glycogen into 1-P-glucose.CAMP can makeGlycogen synthasePhosphorylation leads to the conversion of active glycogen synthase a into inactive glycogen synthase b, thereby inhibiting glycogen synthesis.CAMP can also activate phosphofructose kinase, a key enzyme in glycolysis, and catalyze fructose 6-phosphate to produce fructose 1,6-H phosphate.In addition, cAMP can prevent ATP from inhibiting fructose phosphate.In addition, CAMP can also activate fatty protein kinase through PKA to phosphorylate fatty acid, the key enzyme of fat hydrolysis, so as to promote the hydrolysis of fat into glycerol andfree fatty acids。Fatty acids are transferred into the blood, combined in serum albumin, and then transferred to other tissues, especially the heart, muscle, kidney and other tissues, entering the oxidation and tricarboxylic acid cycle, producing ATP as the energy of cells.CAMP can also activate carbonic anhydride protein kinase, which can phosphorylate carbonic anhydrase and activate it, catalyze CO2 to form carbonic acid, which is then decomposed to release H+, playing an important role in regulating the acid-base balance of cells, and this process can increase gastric acid, which is conducive to digestion (Yi Jianhua, 1981; Sun Daye et al., 1997).
Effects of cyclic adenosine monophosphate on hormone synthesis and secretion
CAMP has the function of regulating neurotransmitter synthesis and promoting hormone secretion (Gerosa, 1980).A large number of experiments have shown that some secondary hormones promote the synthesis of secondary hormones through the cAMP pathway.promoteAdrenocortical hormoneAfter binding to adrenal cortical cells, it activates AC, increases cAMP concentration, and activates PKA, which phosphorylates and activates the synthetases of corticosterone and aldosterone.In ovarian cells, there is a similar situation. Follicle stimulating hormone increases the synthesis of estradiol and progesterone through cAMP pathway (Sun Daye et al., 1997).CAMP can induce the release of GH, thus promoting the synthesis of protein, DNA and RNA in the liver, and can strengthen fat decomposition, stimulating the synthesis of body protein (Dana et al., 1989; Canoed et al., 1985).
Effect of cyclic adenosine monophosphate on immune function
Ruan Hui et al. (2001) found that after the attack of infectious bursal disease virus (IBDV) virulent strain, the activity of the pituitary dorsal gland axis of broilers increased, and there was aSpecific immunityThe increase of serum cAMP content indicates that the increase of cAMP caused by the enhancement of pituitary adrenal axis activity is related to the synthesis of effector macromolecules in the specific immune cells of IBDV patients.
Regulation of cyclic adenosine monophosphate on membrane protein activity
CAMP can promote the phosphorylation of some proteins on the membrane of non nerve cells, change their configuration, and thus regulate the permeability of the membrane to some substances.For example, in red blood cells, cAMP activates the protein kinase on the cell membrane, phosphorylates the Spectin protein on the membrane, and plays an extremely important role in regulating the physical and chemical properties of red blood cell membrane and the morphology of red blood cells.In platelets, cAMP can effectively stimulate the phosphorylation of a 22000 molecular weight protein on the membrane through APK, and regulate platelet aggregation, contraction and other functions by affecting calcium intake.stayCardiac myocyteCAMP can phosphorylate the calcium channel of cardiac myocytes, increase the permeability of membrane to Ca2+, lead to the increase of Ca2+influx, increase the myocardial contractility, and accelerate the heart rate.In the kidney test, vasopressin and others changed the physical properties of cell membrane through cAMP to increase the absorption of water (Yi Jianhua, 1981; Sun Daye and others, 1997).
Effect of cyclic adenylate on nerve cells
McAfee (1971) first proved that cAMP was involved in ganglion synaptic transmission.At present, it is believed that when some nerve cells are excited, the presynaptic nerve terminals release neurotransmitters that act on the corresponding receptors on the postsynaptic membrane and activate AC, synthesize cAMP on the postsynaptic membrane, and then activate PKA, and change the permeability of the membrane to ions through phosphorylation of membrane proteins, thus affecting the excitability of the nerve cells.The nerve tissue contains high levels of cAMP and its metabolic regulating enzymes.There are a large number of cAMPs in the brain, spinal cord, cerebrospinal fluid and peripheral nerves.In vertebrate brain, cAMP content is the highest, and non nerve tissue is about 10 times higher, AC and cAMPphosphodiesteraseThe content is 10-20 times higher than that of other tissues.The above shows that the speed of synthesis and decomposition of CAMP in neural tissue is far higher than that in other tissues, and cAMP plays an important role in neural tissue (Sun Daye et al., 1997).
AMP is an important gene expression regulator (Monall, 1991).CAMP is considered to be directly activated in prokaryotesRNA polymeraseTo promote transcription, that is, to promote InRNA transcription through phosphorylation of the enzyme's 6 factors.Recent research shows that,Eukaryotic cellThe function of cAMP is related to the regulation of transcription factors.Montndny et alele。nt，CRE），It is an important site for these genes to recognize cAMP signals.At the same time, they also found that the target gene expression induced by cAMP also needs PKA activation.The increased level of cAMP activates PKA, which may mediate gene expression induced by cAMP by phosphorylating some specific transcription factors (Montndny et al., 1986).Many experiments have shown that PKA can phosphorylate histones, and the phosphorylated histones are separated from DNA due to the change of charged state and conformation, thus relieving the inhibition of histones on this gene and enabling transcription.In addition, PKA can phosphorylate non histones in vitro. The phosphorylated acidic proteins are more acidic and have more negative charges. They have strong affinity with positively charged histones and combine with each other to separate histones from DNA, remove the inhibition of histones on DNA and transcribe (Yi Jianhua, 1981; Sun Daye et al., 1997).
Cyclic adenylate paircell proliferationCell proliferation and differentiation are two basic characteristics of cells.Proliferation includes cell growth, DNA replication and cell divisioncell cycleTo achieve.Differentiation means that the DNA in cells is transcribed into InRNA, and then further synthesize specific proteins (enzymes), ultimately leading to various differences in cell morphology, structure, biochemical composition and function.Cell proliferation and differentiation are a pair of interrelated and contradictory processes, and cAMP plays an important role in regulating this contradiction (Burgering et al., 1995; Dumont et al., 1989).CAMP can inhibit cell division and promote differentiation in vitro.Therefore, any factor that can increase the content of cAMP in cells can reduce the growth rate of cells,Suppressor cellAnd promoteCell differentiation。Miyasaki (1992) believed that cAMP hadcell proliferationIt has dual effects, that is, it promotes cell proliferation in GO or early G1 phase, and inhibits cell proliferation in late G1 phase.
In addition, cAMP has a certain relationship with tumors. The content of cAMP in normal cells and tumor cells is different, and cAMP in tumor cells is generally lower than that in normal cells.
Application in animal husbandry
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CAMP can improve the production performance of animals and improve the quality of livestock products.The mechanism is that cAMP acts as a hormoneSecond MessengerActivates protein kinase to enhance the activity of metabolic enzymes, thus strengthening the synthesis of protein in the body and accelerating the growth of animals;Induce the synthesis of hormones (such as growth hormone) or enzymes, and promote the anabolism of the body.
Application of cyclic adenylate in meat production
A large number of experimental results show that cAMP has the same effect on growth performance and carcass quality of pigs, sheep, rabbits, etc. High levels of cAMP can cause the activation of HSL in adipose tissue and enhance fat decomposition ability (Ecan et al., 1992).At the same time, cAMP can also reduce insulin andfat cellsAnd MillS, 1990) to counteract the promoting effect of insulin on body fat deposition.Yang Zaiqing et al. (1992) injected cAMP or aminophylline (PDE inhibitor) under the skin of pigs, which not only improved the body composition, but also increased the lean meat rateEye muscle areaCompared with hind legs, it also increases the lipid content and lipase activity in blood.It is suggested that the decrease of body fat and the increase of blood fat may be related to the increase of lipase activity in the body caused by cAMP, and the large amount of decomposition and utilization of body fat is conducive to the reduction of protein decomposition, thus strengthening protein
Deposition in the body (Yang Zaiqing et al., 1992).CAMP also has obvious growth promoting effect on young livestock.Gao Shizheng (1997) reported that the injection of cAMP preparations and standard preparations into piglets, lambs and rabbits had significant growth promoting effects.Li Zixin et al. (1993) had a significant weight gain effect on meat rabbits injected with cAMP, but the effect decreased with the extension of the use time.In addition, cAMP can significantly increase the wool yield and wool fiber length of sheep, and change theamino acidContent (Black et al., 1979).
Application of cyclic adenylate in milk rich production
It has been found that cAMP plays an important role in the physiological process of lactation by studying the mammary glands and cAMP in milk of rats, mice, guinea pigs, rabbits, dairy animals (cows, dairy sheep) and other animals.Wang Qiufang et al. (1993) reported the changes of cAMP in goat milk at different lactation stages, which did not fluctuate before delivery but increased sharply after delivery;During lactation maintenance period, the concentration of cAMP in milk remained at a high level 15 days after delivery;At the peak of lactation, cAMP increased;During the hypolactation period, about one month before stopping milking, sheep became pregnant, milk production decreased significantly, and cAMP in milk decreased significantly.They believe that cAMP mainly promotes the secretion of milk, and cGMP mainly promotes the production of milk, both of which show a fluctuation.Sun Yanming et al. (2002) reported that within a certain concentration range, cAMPin vitro cultureGoat mammary glandepithelial cellsThe proliferation was promoted in a dose-dependent manner, but it was inhibited when cAMP concentration was too high.How cAMP regulates milk production and lactation in breast cells is still unclear.
Application of cyclic adenylate in poultry production
Exogenous cAMP can significantly promote the growth of Avian broilers, increase the breast muscle rate, leg muscle rate, reduce the abdominal fat rate, and increase with the increase of dose (Zhang Fumei et al., 2001).CAMP also has an effect on metabolism of broilers, which can reduce fat deposition in meat, promote protein accumulation, and have a similar effect on liver tissue (Zhang Fumei et al., 2000).CAMP to poultryFat metabolismThe role andMammalsDifferent.CAMP can promote mammalianHormone sensitivityThe increased activity of lipase (HSL) promotes the decomposition of body fat and the increase of blood lipid content, thus reducing the fat deposition in meat and improving the body quality. In poultry, glucagon is the mainLipolytic hormone。Niu Shuling et al. (1998) showed that exogenous cAMP could promote the secretion and metabolism of GH in broilers to a certain extent, and the mortality rate was lower in the test group when the growth was significantly faster than that in the control group, which may be related to the regulatory effect of cAMP on the cardiovascular system of broilers, and on the other hand, the protein content in serum was significantly higher than that in the control group,Especially the increase of globulin.CAMP can also significantly improve the laying performance of layers and improve the quality of eggshells (Niu Shuling et al., 2000).
