China
Africa
Explore chapters and articles related to this topic
Nonalcoholic Fatty Liver Disease
Published in Nicole M. Farmer, Andres Victor Ardisson Korat, Cooking for Health and Disease Prevention, 2022
Fat accumulation in the liver also can be stimulated by fructose consumption inducing oxidative stress in the mitochondria. Acontinase-2 and enoyl CoA hydrase are enzymes found in the mitochondria that are sensitive to oxidative stress (Jensen et al. 2018). Fructose and uric acid decrease acontinase-2 activity, leading to the accumulation of citrate, which moves into the cytoplasm, stimulates ATP citrate lyase, and activates lipogenesis (Jensen et al. 2018). This can also impair fatty acid oxidation by decreasing enoyl CoA hydratase-1 activity, which stimulates AMP Deaminase-2 and reduces AMP-activated protein kinase, which regulates enoyl CoA hydratase-1. This results in accumulation of fat and stimulation of gluconeogenesis (Jensen et al. 2018).
Supplying Muscle Machines with Energy
Published in Peter W. Hochachka, Muscles as Molecular and Metabolic Machines, 2019
The notable interspecies differences raise serious questions on the functions of AMP deaminase in species that possess it. The most likely answer is that by supplying IMP for adenylsuccinate synthetase, AMP deaminase sets the stage for fumarate formation from aspartate and, thus, for augmenting Krebs cycle intermediates when they are needed. This would explain the occurrence of this enzyme in vertebrate muscles, as well as its absence in invertebrates, where proline and glutamate are abundant and serve anapleurotic roles (De Zwaan, 1983; Storey and Storey, 1983). It also explains why IMP is a potentially adaptive end product of aerobic metabolism.
Purine, pyrimidine and porphyria disorders
Published in Steve Hannigan, Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
Myoadenylate deaminase deficiency is a rare metabolic disorder that is characterised by a deficiency of the muscle enzyme adenosine monophosphate (AMP) deaminase enzyme. AMP deaminase and the purine nucleotide cycle have an important role in providing energy for skeletal muscles during exercise. There are two forms of myoadenylate deaminase deficiency, namely an acquired form and an inherited form. This summary will focus on the inherited form.
Recent approaches to gout drug discovery: an update
Published in Expert Opinion on Drug Discovery, 2020
Naoyuki Otani, Motoshi Ouchi, Hideo Kudo, Shuichi Tsuruoka, Ichiro Hisatome, Naohiko Anzai
Enhanced ATP degradation in cells leads to adenosine diphosphate (ADP) or AMP accumulation, which accelerates purine degradation converting to urate. Alcohol consumption promotes ATP conversion to AMP, resulting in an increased urate production [8]. Urate excretion into the urine may also be reduced due to the dehydration and metabolic acidosis associated with alcohol consumption. It has been observed that excessive intake of fructose may cause not only fatty liver and insulin resistance, but also increased urate levels. Fructose is rapidly phosphorylated in the liver, but inorganic phosphorus decreases with ATP consumption. Thus, ATP re-synthesis using inorganic phosphorus is reduced, but AMP deaminase activity, normally suppressed by inorganic phosphorus, is increased, accelerating AMP degradation through IMP and increasing urate levels. Even in an ischemic state, ATP degradation is accelerated, and urate production is increased. Furthermore, urate production increases when bone marrow cells are in a hyperproliferative state, such as in hemolytic anemia or myeloproliferative diseases, and large quantities of nucleotides are released due to tumor cell destruction during chemotherapy, resulting in increased serum urate levels.
From omics technologies to personalized transfusion medicine
Published in Expert Review of Proteomics, 2019
Similarly, hypoxanthine levels negatively correlate with post-transfusion recoveries in mice and humans [64]. As ATP levels plummet during refrigerated storage, the AMP derived from ATP consumption and breakdown becomes the substrate of erythrocyte-specific AMP deaminase 3, which is activated by oxidative stress and generates IMP and its breakdown product hypoxanthine. Tracing experiments suggest that minimum residual purine salvage activity is present in mature erythrocytes, while attenuation of AMP deamination can be obtained through hypoxic storage or enzymatic inhibition of purine deminases [64]. Hypoxanthine levels raise to ~700–1000 µM by the end of storage [57,64,89], levels sufficient to trigger xanthine oxidase activation and the subsequent generation of the toxic hydrogen peroxide. Notably, supplementation of purine nucleosides inosine and guanosine can rescue low DPG levels by feeding a ribose phosphate moiety into the non-oxidative branch of the pentose phosphate pathway, as experimented through rejuvenation [90] and alternative additives [51,55]. However, the purine moieties of these nucleosides aggravate intra- and extra-cellular hypoxanthine contents (via mechanisms of simple phosphoribolysis or activation of hypoxanthine-guanosine phosphoribosyl transferase for inosine and guanosine, respectively), making it necessary to add an extra wash step prior to transfusion into the recipient at least in the case of rejuvenation [91].
Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport
Published in Expert Review of Proteomics, 2018
Travis Nemkov, Julie A. Reisz, Yang Xia, James C. Zimring, Angelo D’Alessandro
Similarly, metabolic byproducts of RBCs could impact responses in both immature erythroblasts or mature erythrocytes. For example, purine deamidation by purine deminases (such as RBC-specific AMP deaminase 3) occurs in response to oxidative stress [69], promoting the accumulation of IMP (and its breakdown product hypoxanthine) and negatively impacting ATP/AMP ratios, thus activating AMPK and some of the responses highlighted above. Notably, hypoxanthine is released in the plasma, where it becomes a substrate for xanthine oxidase, an enzyme that generates xanthine and urate in reactions that also produce the r potent ROS hydrogen peroxide. Therefore, pro-oxidant stimuli conferred by impaired antioxidant defense in sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, drug treatment, and blood bank storage could each promote hypoxanthine release and propagation of the pro-oxidant stimulus to other (red blood) cells. In so doing, urate accumulation in plasma would also result in product-induced inhibition of xanthine oxidase, thereby limiting the amplitude of the oxidative lesion to other cells. Interestingly, serum urate levels correlate with better RBC storage parameters [111], indicating that paracrine signaling in RBCs may have functional outcomes.