Cyclic AMP
Cyclic AMP (cAMP) is a signaling molecule that plays a crucial role in various cellular processes. It is formed from ATP and acts as a second messenger, transmitting signals from hormones and neurotransmitters to regulate processes such as metabolism, gene expression, and cell growth. cAMP exerts its effects by activating protein kinase A and other downstream signaling pathways.
6 Key excerpts on "Cyclic AMP"
- Gerhard Krauss(Author)
- 2014(Publication Date)
- Wiley-VCH(Publisher)
...Via enzymatic pathways, large amounts of messenger substances can be repeatedly and rapidly created and inactivated. Messenger substances, such as Ca 2+, may be stored in special storage organelles, from which they can be rapidly released by a signal. Messenger substances may be produced in a location-specific manner, and they may also be removed or inactivated according to their location. It is therefore possible for the cell to create signals that are spatially and temporally limited. 8.2 Cyclic AMP Summary The second messenger 3′,5′-Cyclic AMP (cAMP) is produced from ATP by the action of adenylyl cyclases, and is degraded by the action of phosphodiesterases. The signaling function of cAMP is based primarily on binding to protein kinase A (PKA), ion channels, and the transcription factor Epac. To a large part, signaling by cAMP is restricted to discrete locations at the cell membrane and intracellular membrane compartments where cAMP production, binding to its target proteins and cAMP degradation each occur within defined supramolecular complexes organized by specific anchoring proteins such as the A-kinase anchoring proteins (AKAPs). 3′,5′-Cyclic AMP (cAMP), which is produced from ATP by the action of adenylyl cyclases (ACs; see Section 7.7.1 and Figure 7.30), influences many cellular functions including gluconeogenesis, glycolysis, lipogenesis, muscle contraction, membrane secretion, learning processes, ion transport, differentiation, growth control, and apoptosis. The concentration of cAMP is controlled primarily by two means, namely via new synthesis by ACs and via degradation by phosphodiesterases. Both enzymatic activities cooperate in forming cAMP gradients in the cell with specific temporal and local characteristics. An important feature of cAMP signaling is the colocalization of the enzymes of cAMP metabolism and the targets of cAMP...
eBook - ePub- Anthony W. Norman, Gerald Litwack(Authors)
- 2014(Publication Date)
- Academic Press(Publisher)
...Although several theories exist for the activation reaction mechanism, this subject is in its infancy. J Second Messengers A second messenger is a substance whose actual or relative concentration increases inside the cell in response to the primary hormone. Its function is to convey the primary hormonal signal and to translate it into metabolic changes within the target cell. Examples of second messengers are as follows: Cyclic AMP, cyclic GMP, calcium ions (with or without calmodulin), arachidonic acid, inositol triphosphate, diacylglycerol, and messengers that apparently regulate phosphoprotein phosphatases. Examples of hormones which stimulate Cyclic AMP levels are typified in the general mechanism shown in Fig. 1-22A. Figure 1-22B shows a more detailed model of protein kinase, including the interaction sites between the R (regulatory) and C (catalytic) subunits. The elevated levels of Cyclic AMP in the cell cytoplasm lead to the activation of protein kinase(s) (Fig. 1-15) and the phosphorylation of specific proteins. The net reaction for activation of protein kinase by Cyclic AMP can be written as Figure 1-22 (A) Overview of the mechanism of activation of a protein kinase by elevated cytosolic levels of Cyclic AMP. H, Hormone; N, guanine nucleotide binding protein; P, phosphate; R, regulatory subunit; C, catalytic subunit; cAMP, Cyclic AMP. (B) Biochemical details of the activation of protein kinase II from porcine heart. The inactive protein kinase is diagrammed on the left and shows the accessible sulfhydryl groups and the biochemical nature of the sites of interaction between the regulatory (R) and catalytic (C) subunits (boxed inset). The portion of the R subunit shown in the inset includes the autophosphorylation site (Ser-95) followed by Cys-97. On the right side is drawn the activated catalytic subunits with the R Cyclic AMP complexes above. Reproduced from N. C. Nelson and S. S...
eBook - ePub- Graham F. Hatfull, William R. Jacobs, Graham F. Hatfull, William R. Jacobs(Authors)
- 2014(Publication Date)
- ASM Press(Publisher)
...Gwendowlyn S. Knapp 1 Kathleen A. McDonough 1, 2 14 Cyclic AMP Signaling in Mycobacteria Cyclic AMP IS A UNIVERSAL SECOND MESSENGER USED BY PATHOGENS AND THEIR HOSTS The ability to sense and respond to changing environments is essential for all organisms, and this process is mediated through signal transduction. The small molecules that relay signals from receptors to one or more effector proteins within the cell during signal transduction are called second messengers. Cyclic nucleotides, (p)ppGpp, Ca2 +, inositol triphosphate, and diacylglycerol function as second messengers in different types of cells. Cyclic 3′,5′-AMP (cAMP) is one of the most widely used second messengers, and its presence in bacteria, archaea, fungi, eukaryotic parasites, and mammals provides numerous opportunities for cAMP-mediated modulation of host-pathogen interactions (1 – 5). cAMP signaling in mammals controls biological processes ranging from metabolism to memory formation and innate immunity, although it was first discovered for its role in hormone signal transduction (1, 6, 7). In bacteria, cAMP is best known for its role in mediating the “glucose response,” or catabolite repression in Escherichia coli (2, 8). However, cAMP is also a critical regulator of virulence for many bacterial and fungal pathogens (9). This chapter discusses the many roles of cAMP signaling in mycobacteria, including the regulation of gene expression and manipulation of host cell signaling during infection. cAMP is generated from ATP by adenylyl cyclases (ACs) and hydrolytically degraded by phosphodiesterases (PDEs) (Fig. 1). ACs are distributed among six classes based on their primary amino acid sequences, with the well-studied bacterial AC from E. coli being a member of class I. The secreted AC toxins from Pseudomonas aeruginosa, Bacillus anthracis, and Bordetella pertussis (10 – 12) belong to class II, and classes IV to VI each contain a very small number of representatives from assorted bacteria (13 – 17)...
eBook - ePubChemical Senses
Receptor Events and Transduction in Taste and Olfaction
- Joseph G. Brand(Author)
- 2021(Publication Date)
- CRC Press(Publisher)
...In the case of secreted products, new first messengers are generated. These messengers produce the characteristic biological responses of the cell via a cascade of biochemical reactions leading to processes such as secretion, alteration in membrane conductance, and changes in metabolism. We are beginning to realize that even though these sequences are complex, the cell can precisely control its response to these signals. One of the first of the transduction mechanisms discovered (Sutherland and Rail, 1958) was the now well-documented adenylate cyclase system, in which the hormone or transmitter generates the second messenger, Cyclic AMP. Cyclic AMP has many actions, mainly through its activation of kinases. Other second-messenger systems have since been identified, such as those using inositol phosphates, diacylglycerol, calcium, and arachidonic acid; and like cAMP, each has one or more specific target activities in the cell. Much has been learned about the molecular events that link receptor-transducing systems to effector systems that generate second messengers. While each receptor-transduction sequence produces unique biological responses, there are many mechanistic similarities among all systems. II. GTP-BINDING PROTEINS In the early 1970s it was recognized that there was a transducer system that linked the receptor to the adenylate cyclase. This intermediary was found to be a GTP-binding protein (G-protein) converting GTP to GDP (Rodbell, 1980). This general scheme for transducing extracellular signals into a cellular response seems now to be common to many receptor-mediated processes, and recent reviews have discussed the specifics of this process (Gilman, 1987; Neer and Clapham, 1988). These G-proteins were found to be not only stimulatory but also inhibitory (Rodbell, 1980). The stimulatory signals convert ATP to cAMP via a stimulatory G-protein, termed G s. Other receptors act to inhibit formation of cAMP via an inhibitory G-protein, G i...
- Karen Birch, Keith George, Don McLaren(Authors)
- 2004(Publication Date)
- Routledge(Publisher)
...B4 Control of Energy Sources DOI: 10.4324/9780203488249-11 Key Notes Metabolic regulation Metabolism is regulated through control of key enzymes involved in energyproducing or energy-storage processes. The control is mediated by hormones which, via cAMP, activate inactive enzymes. However, enzyme activity can also be affected by allosteric effectors. Hormones and Cyclic AMP Hormones are chemical substances originating from glandular cells which are then transported through blood to a target cell to influence physiological activity. Examples of key hormones which influence the metabolic activity of a cell include adrenaline (epinephrine), noradrenaline (norepinephrine), insulin, and glucagon. Cyclic AMP (cAMP) is a ubiquitous intracellular effector molecule produced from ATP by the enzyme adenylate kinase. Cyclic AMP activates a protein kinase within cells, which in turn activates inactive enzymes. In some instances (e.g. glycogen synthase) cAMP production inhibits the activity of an enzyme. Production of cAMP occurs as a consequence of hormonal activation. Allosteric effectors Some molecules found in cells are able to promote or inhibit the activity of regulatory enzymes. Such molecules, known as allosteric effectors, do not bind to the active site of an enzyme and as such are distinct from competitive inhibitors. Related topics The endocrine system (F2) Integrated control of exercise (F3) Metabolic regulation To ensure that ATP is provided rapidly or slowly, there needs to be regulation of the metabolic processes. Such regulation is normally controlled during steady-state exercise by circulating hormones secreted by endocrine glands such as the adrenal glands or the pancreas. The hormones secreted by these glands include adrenaline (epinephrine), noradrenaline (norepinephrine), glucagon, and insulin, and they mediate their effects by activating inactive enzymes present within the cell...
eBook - ePub- ljsbrand M. Kramer(Author)
- 2015(Publication Date)
- Academic Press(Publisher)
...Reflecting this history, Cyclic AMP was said to be the first second messenger and Ca 2+ the second. In fact, elevation of cytosol Ca 2+ is more ubiquitous than is the elevation of Cyclic AMP, and it regulates a very diverse range of activities, including secretion, muscle contraction, fertilization, gene transcription, and cell proliferation (return to Chapter 3, “Regulation of Muscle Contraction by Adrenoceptors” and Chapter 4 “Cholinergic Signaling and Muscle Contraction”). Free, bound, and trapped Ca 2+ In the biological world, Ca 2+ may be considered to exist in three main forms: trapped, bound, and free. In vertebrates, calcified tissues such as bones and teeth account for the major proportion of body calcium (mineralized tissues). Within these tissues calcium is trapped in mineral form (with phosphate) as hydroxyapatite (Ca 5 (PO 4) 3 (OH)). Apart from its structural function, bone provides a reservoir of slowly exchangeable calcium that can be mobilized, when needed, to maintain a steady extracellular concentration (Figure 6-1). The total amount of calcium in extracellular fluid, in comparison with the mineralized tissues, is very small (mM range) and of this, only about half can be regarded as free. The remainder is bound mostly to proteins in the extracellular milieu. Within cells, the concentration of free Ca 2+ inside the cytosolic compartment is still lower (nM range), by about four orders of magnitude (Figure 6-1). The cell organelles may contain higher levels of free Ca 2+, in particular the endoplasmic reticulum and endo/lysosomes (high μM range). In this chapter, we focus on cellular proteins that bind Ca 2+ and which serve different roles. As we will learn some of the proteins simply sequester Ca 2+, but most of them are components of Ca 2+ -regulated signaling pathways...
