Synapses
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
To gain a better understanding of second-messenger systems, it is necessary to review first some biochemistry in order to explain the structure of an important, typical second-messenger cyclic AMP (cAMP) and the guanine-derived phosphates. It should be recalled that two of the basic constituents of nucleic acids are the purine compounds adenine and guanine. When attached to the 1ʹ carbon atom of a ribose sugar molecule (Figure 6.10), they become the nucleosides adenosine and guanosine, respectively. When a single phosphate group is attached to the 5ʹ carbon atom of a ribose sugar molecule, these nucleosides become the nucleotides adenosine monophosphate (AMP) and guanosine monophosphate (GMP), respectively. However, another phosphate group can attach to the first phosphate group to give adenosine diphosphate (ADP) and guanosine diphosphate (GDP), respectively. The attachment of a third phosphate group to the second phosphate group, gives adenosine triphosphate (ATP) and guanosine triphosphate (GTP), respectively.cAMP molecule.
Signalling Pathways in The Regulation of Cellular Responses to Exercise
Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse in The Routledge Handbook on Biochemistry of Exercise, 2020
Conserving cellular ATP levels during muscle contractions is vital to maintain cell function. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is highly responsive to metabolic perturbations and is acutely activated to re-establish cellular energy homeostasis through phosphorylation of key metabolic enzymes. AMPK activation turns on catalytic ATP-generating processes while inhibiting anabolic processes such as lipid and protein synthesis. The highly conserved AMPK is a heterotrimeric kinase consisting of a catalytic α as well as a regulatory β and γ subunit, all of which are found in multiple isoform complexes (45, 111). AMP-binding sites and a glycogen-binding domain are contained within the β subunit, which presumably acts to inhibit the activity of the kinase when glycogen stores are abundant (97). AMPK is allosterically inhibited by creatine phosphate and activated several-fold by an increase in cytosolic AMP/ATP ratio (11, 31). Binding of AMP to AMPK allows exposure of the threonine residue on the α subunit, which is phosphorylated by the upstream AMPK kinases constitutively active tumour suppressor liver kinase B1 (LKB1)(133) and CAMK kinase β (48, 132) (Figure 8.2).
Control of blood vessels: intrinsic control
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
The vasodilator adenosine may account for ~20%-40% of the sustained phase of metabolic hyperaemia in exercising skeletal muscle, and contributes to myocardial hyperaemia. Adenosine is formed in active myocardium and skeletal muscles by the dephosphorylation of extracellular adenosine monophosphate (AMP) by AMP 5’-nucleotidase, an ectoenzyme (outward facing enzyme). AMP, a breakdown product of ATP, is released into the extracellular fluid in increasing amounts during exercise or systemic hypoxia. Adenosine causes vasodilatation through multiple pathways:A2A receptors on vascular myocytes activate the adenylate (or adenylyl) cyclase-cAMP-protein kinase cascade (Figure 12.10).A1 receptors are coupled to KATP channels, leading to hyperpolarization-mediated relaxation.Adenosine binds to receptors on sympathetic varicosities to reduce NAd release (Figure 14.2).
Association between macronutrient intake and amyotrophic lateral sclerosis prognosis
Published in Nutritional Neuroscience, 2020
Boeun Kim, Youri Jin, Seung Hyun Kim, Yongsoon Park
Dorst et al.17 reported that an isocaloric oral supplement containing 35% of calories from fat more effectively increased the body weight of ALS patients than a supplement containing 0% of calories from fat during 12 weeks of supplementation. However, Wills et al.19 found that a high-fat hypercaloric tube-fed diet (55% fat, 28% carbohydrate, and 17% protein) had no significant effect on body weight and survival compared with a control isocaloric tube-fed diet (29% fat, 54% carbohydrate, and 17% protein) in ALS patients, suggesting that the formula containing 55% calories from fat lowered the tolerability of the enteral diet and increased the rate of gastrointestinal malabsorption. The present study indicated that short-term survival and the survival time were associated with fat intake. In transgenic ALS mice, a high-fat diet containing 21–47% of calories from fat resulted in higher body weights and longer survival times than a standard diet containing 4–18% of calories from fat.26–29 Adenosine monophosphate-activated protein kinase (AMPK) activity was lower, heat shock protein-70 expression was greater, motor neuron loss was lower, disease onset was later, and survival was longer in transgenic ALS mice fed a high-fat diet than in those fed a standard diet.29 Additionally, delayed AMPK activation reduced the need for energy production, which prolonged the lifespan of transgenic ALS mice fed a high-fat diet.26
Protective effect of aminoguanidine against lipopolysaccharide-induced hepatotoxicity and liver dysfunction in rat
Published in Drug and Chemical Toxicology, 2021
Farimah Beheshti, Mahmoud Hosseini, Mehdi Taheri Sarvtin, Ali Kamali, Akbar Anaeigoudari
Furthermore, NO is a highly reactive oxidant, which is produced by liver parenchymal and nonparenchymal cells by nitric oxide synthase (NOS) (Al-Shabanah et al. 1999). It has been reported that toxicological effects of NO may take place through peroxynitrite and oxidative stress induction (Sandoval et al. 1997). It has been also suggested that overproduction of NO and oxidative stress caused by LPS can result in severe hepatic injury (Morikawa et al. 1999). In addition, NO produced by inducible NO synthase (iNOS) has been shown to play an important role in the development of hepatocytes programmed death (Osakabe et al. 2002). It has been also reported that the mice lacking iNOS gene were protected against acetaminophen- caused liver injury (Bourdi et al. 2002). Researches also showed that glucagon and cyclic adenosine monophosphate ameliorated liver injury induced by acetaminophen via down-regulating iNOS (Kelava et al. 2013). All of these findings confirm that iNOS has an important role in liver dysfunctions. According to this scientific evidence, it was assumed that blockade of iNOS by AG might prevent the inflammatory responses and oxidative stress caused by LPS to improve liver function in rats. Interestingly, inhibition of iNOS by AG ameliorated LPS-caused liver dysfunction in rats. In supporting this claim, the serum level of ALK-P, ALT and AST enzymes was lower in LPS-AG groups than LPS group. In addition, the serum level of albumin in LPS-AG groups also was higher than LPS group. However, more precise experiments need to be done to see the cell viability after treatment.
Clinical significance of myositis-specific autoantibodies
Published in Immunological Medicine, 2018
Anti-cytosolic 5′ nucleotidase 1A (cN1A) was described in 2011 by Salajegheh et al. [102] as an autoantibody against a 43 kDa protein associated with inclusion body myositis (IBM). The corresponding autoantigen was identified as cN1A expressed in skeletal muscle [103,104]. This autoantigen has a role in the hydrolysis of adenosine monophosphate leading to the physiological homeostasis of energy, metabolic regulation and cell replication. Anti-cN1A is present in about 33–34% of IBM, 4–5% of PM and 3–4% of DM cases [103,104]. Because Herbert et al. [105] showed that this autoantibody was present in 36% of Sjogren’s syndrome and 20% of SLE cases, the specificity of this autoantibody for myositis is probably low. However, it might help differentiate between myositis subgroups. In a recent study, the pathogenic role of anti-cN1A in IBM was demonstrated both in vivo and in an in vitro passive immunization model suggesting that the autoantibody might affect protein degradation in myofibers [106].