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Genetics of Obesity: Overview and Research Directions
Published in Claude Bouchard, The Genetics of Obesity, 2020
The data on linkage between obesity phenotypes and candidate genes or other molecular markers are even less abundant. The currently available results are summarized in Table 4. Significant linkage has been found with markers at the adenosine deaminase, Kell, esterase D, and α-2 and β-loci of the Na/K ATPase and 3-β-hydroxy steroid dehydrogenase genes. Lack of linkage has been reported for GLUT1 and the α-1 locus of the Na/K ATPase. Conflicting results have been obtained for adenylate kinase-1.
Human Erythroenzymopathies Of The Anaerobic Embden-Meyerhof Glycolytic And Associated Pathways
Published in Ronald L. Nagel, Genetically Abnormal Red Cells, 2019
Ernst R. Jaffé, William N. Valentine
The identification of G6PD deficiency as the necessary precondition for most instances of “oxidant-induced” erythrocyte destruction in 1956,3 or as a prerequisite for some cases of spontaneous hemolysis and the discovery in 1961 of PK deficiency, the most common glycolytic enzyme defect associated with chronic hemolysis,4 stimulated active and productive investigations in search of other erythrocyte enzyme aberrations associated with premature erythrocyte destruction. With the virtual exhaustion of glycolytic and HMP shunt enzyme deficiencies for biomedical scientists to find, attention has turned to hereditary defects in enzymes not directly involved in the metabolism of glucose. The maintenance of adenine nucleotides, essential cofactors for glycolysis, is dependent upon both glycolysis and enzymes that can function in their salvage. Thus, marked deficiency in the activity of adenylate kinase (AK) may result in a hemolytic disorder similar to that seen in anaerobic glycolytic enzyme deficiencies. In contrast, excess activity of adenosine deaminase (ADA) is associated with significantly reduced erythrocyte ATP levels and a hemolytic syndrome. More remote from the glycolytic pathway are the degradative enzymes of nucleotide metabolism. Severe, genetically determined deficiency of erythrocyte pyrimidine-5′-nucleotidase (P5N) is associated with a moderately severe hemolytic disorder and enormous accumulations of uridine and cytidine nucleotides and their derivatives in the erythrocytes. These disorders will also be reviewed here.
Victor McKusick (1921–2008)—Father of Medical Genetics
Published in Krishna Dronamraju, A Century of Geneticists, 2018
Victor once wrote: “I am not certain why, in the late 1950s, I became enthralled with mapping genes on human chromosomes” (McKusick 2006). One of his first attempts at gene mapping was in collaboration with Ian Porter, which involved the map distance between the loci for G6PD deficiency and colorblindness on the X chromosome. Linkage studies in the Moore Clinic continued in the 1960s in collaboration with James Renwick, who (with Jane Schulze and David Bolling) wrote one of the first computer programs for linkage analysis. It was used in the analysis of possible linkage of XG and CB. Renwick was also involved in several other Moore Clinic linkage studies, including assignment of the Duffy blood group locus to chromosome 1 in 1968, first assignment of a specific locus to a specific autosome. Other linkage studies from the Moore Clinic included mapping of the interval between nail-patella syndrome and the adenylate kinase locus.
Effect of eccentric exercise on markers of muscle damage in patients with chronic obstructive pulmonary disease
Published in Physiotherapy Theory and Practice, 2021
Aqsa Mujaddadi, Jamal Ali Moiz, Deepika Singla, Irshad Hussain Naqvi, Mir Shad Ali, Deepak Talwar
In both the groups, CK levels peaked at 48 h following eccentric exercise which is in contrast to a previous study (Camillo et al., 2015) which showed an increase in CK following downhill walking in patients with COPD. Although in the present study, activity of CK increased in patients with COPD following eccentric exercise, this increment was insignificant between the groups This might be due to depressed CK activity in COPD patients at baseline which is in contrast with a previous study (Barreiro, Gea, Matar, and Hussain, 2005). One possible speculation for this can the pattern and intensity of limb muscle recruitment which changes in a way that reduces the reliance of muscle fibers on phosphocreatine (Pcr) to buffer Adenosine Triphosphate (ATP). These alterations in muscle substitute the Pcr by adenylate kinase family proteins that catalyze the “myokinase reaction” which ultimately results in depressed CK activity within the muscle fibers (Andrade et al., 2003). Another reason behind depressed CK activity may be excessive reactive oxygen species formation in COPD muscles which selectively target CK leading to its inhibition as a result of oxidative modifications in critical residues present within the enzyme (Mihm et al., 2001).
CD73 as a potential opportunity for cancer immunotherapy
Published in Expert Opinion on Therapeutic Targets, 2019
Ghasem Ghalamfarsa, Mohammad Hossein Kazemi, Sahar Raoofi Mohseni, Ali Masjedi, Mohammad Hojjat-Farsangi, Gholamreza Azizi, Mehdi Yousefi, Farhad Jadidi-Niaragh
The cooperative enzymatic function of CD39 and CD73 regulates purinergic signals through conversion of ATP/ADP/AMP to adenosine. This activity attenuates pro-inflammatory condition generated by ATP and converts it into an anti-inflammatory environment by adenosine. Regarding an important role of ATP metabolism in the physiologic processes and signaling and immune homeostasis, it is tightly regulated. While CD39 converts ATP into AMP with just trace levels of ADP, CD73 generates adenosine from AMP [68]. CD39 degrades ATP through phosphohydrolyzing in the presence of Ca2+ and Mg2+ to generate AMP [69]. Generation of AMP from ATP by CD39 is a reversible reaction by a function of two extracellular kinases including NDP kinase and adenylate kinase that facilitate the conversion of ADP to ATP and AMP to ADP, respectively. On the other hand, generation of adenosine from AMP by CD73 is irreversible. However, it can be reversible upon intracellular transport of adenosine via the action of adenosine kinase [52]. ATP and ADP are also competitive inhibitors of CD73 [70,71]. Therefore, it seems that CD73 is a key checkpoint in the metabolism of immune-stimulating ATP and its conversion into immune-regulatory adenosine.
Targeting autophagy enhances heat stress-induced apoptosis via the ATP-AMPK-mTOR axis for hepatocellular carcinoma
Published in International Journal of Hyperthermia, 2019
Jiayun Jiang, Shihan Chen, Kun Li, Chang Zhang, Yunhua Tan, Qingsong Deng, Yuelong Chai, Xiaofei Wang, Geng Chen, Kai Feng, Leida Zhang, Chuan-Ming Xie, Kuansheng Ma
Previous studies showed that heat shock of rat hepatocytes could decrease ATP content, increase the AMP/ATP ratio, and lead to the activation of AMPK by phosphorylation [25]. AMPK is an αβγ heterotrimer activated by decreasing concentrations of ATP and increasing AMP concentrations. In agreement with this finding, sublethal heat stress reduced the ATP level. As the level of ATP decreased, increasing concentrations of ADP resulted in an increase in AMP due to the adenylate kinase equilibrium [26]. Thus, we speculated that the AMP/ATP ratio would increase and activate the AMPK signaling pathway. Our results revealed that sublethal heat stress increased AMPK phosphorylation and decreased the mTOR downstream targets p-p70S6K and p-4E-BP1 in a time-dependent manner, suggesting that the ATP-AMPK-mTOR signaling pathway plays an important role in heat-induced autophagy (Figure 5(A,B)). AMPK induces autophagy via the activation of ULK1 or the inactivation of mTOR [27]. To further validate whether AMPK was involved in autophagy induced by heat stress, the effects of the AMPK activator AICAR and the AMPK inhibitor compound C on autophagy were analyzed in heat-treated cells. Similar to heat stress, AICAR activated AMPK via phosphorylation at Thr172 and induced an increase in LC3-II and a decrease in p62 (Figure 5(C) and Supplemental Figure S3(A)), whereas compound C blocked the effects of heat stress-induced AMPK activation and autophagy (Figure 5(D) and Supplemental Figure S3(B)). Taken together, these results indicate that the ATP-AMPK-mTOR signaling pathway is involved in heat-induced autophagy in HCC cells.