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The Bioenergetics of Mammalian Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Hypotonically treated boar spermatozoa could oxidize extra mitochondrial NADH in the presence of glutamate, aspartate, and malate, or of lactate. Thus, these sperm contain both a malate/aspartate shuttle (Figure 4b)84 and a lactate/pyruvate shuttle. The malate/aspartate shuttle was blocked by transaminase inhibitors and inhibitors of dicarboxylic acid transport. These did not affect the lactate/pyruvate shuttle, which was inhibited by the pyruvate transport inhibitor α-cyanocinnamate. Cyanocinnamate had no effect on the malate/aspartate shuttle.85
Myocardial Metabolism During Diabetes Mellitus
Published in Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla, Heart Dysfunction in Diabetes, 2019
Grant N. Pierce, Robert E. Beamish, Naranjan S. Dhalla
One mechanism proposed to account for some of the abnormalities in oxidative phosphorylative energy production in the heart during diabetes involves alterations in mitochondrial transporter systems. A primary pathway for the transfer of reducing equivalents (H+) from the cytoplasm into the mitochondria is the malate-aspartate shuttle (Figure 8). Because of the relative impermeability of the inner mitochondrial membrane, a complex system of substrate exchanges must occur. Malate may enter or leave the mitochondrial matrix in exchange for α-ketoglutarate via the α-ketoglutarate-malate carrier. In a similar fashion, glutamate may enter or leave the mitochondria matrix in exchange for aspartate via another protein bound to the inner mitochondrial membrane, the aspartate-glutamate carrier. Through the actions of malate dehydrogenase and aspartate amino-transferase in both cytosolic and mitochondrial matrix compartments, H+ is transferred into the matrix and ATP is produced by oxidative phosphorylation.
Mitochondrial Stress and Cellular Senescence
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Irene L. Tan, Michael C. Velarde
NAD+ may also be regulated by controlling malate dehydrogenase activity (MDH). MDH1 is a component of the malate-aspartate shuttle that catalyzes the reduction of oxaloacetate to malate by converting NADH to NAD+ (Lee et al. 2012). Depleting MDH1 in young HDFs and IMR90 human fibroblast reduces NAD+/NADH ratio, inhibits SIRT1, and induces cellular senescence (Lee et al. 2012). Moreover, old human dermal fibroblasts (HDFs) have reduced MDH1 activity and cytosolic NAD+ levels.
Changes of hippocampus proteomic profiles after blueberry extracts supplementation in APP/PS1 transgenic mice
Published in Nutritional Neuroscience, 2020
Hai-qiang Li, Long Tan, Hong-peng Yang, Wei Pang, Tong Xu, Yu-gang Jiang
MDH is an enzyme that catalyzes the last step of the citric acid cycle, the reversible oxidation of malate to oxaloacetate coupled with the reduction of NAD+ to NADH. MDH is located in both the cytosol and the mitochondrial matrix and participates in the malate-aspartate shuttle that passively feeds electrons from cytosolic NADH into the electron transport chain. Loss-of-function of MDH due to oxidative modification would significantly decrease the efficiency of the citric acid cycle as well as the transport of electrons from cytosolic NADH into the mitochondrial matrix, and consequently, decrease the production of ATP.42 MDH was markedly increased in Early Alzheimer’s disease (EAD).43 In our study, the down-regulated expression of MDH might associate with the improving of energy dysfunction.
Exploratory metabolomic analysis based on UHPLC-Q-TOF-MS/MS to study hypoxia-reoxygenation energy metabolic alterations in HK-2 cells
Published in Renal Failure, 2023
Xiaoyu Yang, Ailing Kang, Yuanyue Lu, Yafeng Li, Lili Guo, Rongshan Li, Xiaoshuang Zhou
With the increase in reoxygenation time, the content of most amino acids in HK-2 cells showed an increasing trend and reached a peak at 12h. Notably, the arginine content decreased and reached a trough at 12 h of reoxygenation, in contrast to the trend of the other amino acid contents. Glutamate (Figure 5(A,B)) is one of the kidney’s most important substrates for ammonia production and plays an important role in acid-base homeostasis. HK-2 cells’ mitochondria can oxidize glutamate to α-ketoglutarate, which enters the TCA cycle via transamination and is further converted to succinate, which is used to supplement the impaired TCA cycle [12]. Aspartic acid and arginine (Figure 5(C,D)) were involved in the urea cycle and transported NAD + transport into mitochondria with the malate–aspartate shuttle, which was involved in the tricarboxylic acid cycle, glycolysis, and the electron transport chain [13,14]. In the cells of proximal renal tubules, arginine synthetase acts on citrulline to produce arginine [15]. But the trend of arginine is opposite to that of aspartic acid. The probable cause is a decrease in renal arginine production during unilateral ischemia-reperfusion, a change that may facilitate the recovery of low plasma arginine levels after trauma, shock, or vascular surgery [16]. Transcription factor Krüppel-like factor 6 (KLF6) was strongly induced after AKI. KLF6-mediated inhibition of BCAA catabolism can lead to increased BCAA levels such as Leucylleucine (Figure 5(E)) [17]. D-proline accumulates during renal insufficiency, and proline induces oxidative stress and lipid peroxidation in rat kidneys [18,19]. It has been shown that the greatest fluctuations in amino acid metabolism among metabolic pathways were observed in a renal ischemia-reperfusion model, suggesting that amino acid metabolism may be a significant but unnoticed pathway in the development of IR-AKI [20].
The application of proteomics in muscle exercise physiology
Published in Expert Review of Proteomics, 2020
Stuart J Hesketh, Ben N Stansfield, Connor A Stead, Jatin G Burniston
Mitochondrial samples from HCR/LCR muscle were also enriched for phosphorylated or acetylated peptides and differences in modification status were investigated by LC-MS/MS analysis of TMT-labeled samples [28]. Acetylation rather than phosphorylation emerged as the most prominent difference between HCR and LCR mitochondria. Numerous proteins were less acetylated in HCR than LCR, and the acetylation of some proteins decreased further in HCR mitochondria after exercise. Differences in the acetylation of mitochondrial enzymes were not associated with the abundance of sirtuin-3 deacetylase and may, instead, reflect differences in NAD/NADH ratio in the mitochondria of high- versus low-capacity runners. Mitochondrial malate dehydrogenase (MDHM) emerged as a key enzyme that may be regulated by acetylation. K335 acetylation of MDHM was significantly less in HCR than LCR mitochondria, and K239 acetylation of MDHM decreased significantly after 10 min aerobic exercise specifically in HCR mitochondria. Coincidently, Souza et al. [29] reports reversible oxidation of cysteine residues in HCR and LCR plantaris muscle and found significantly greater oxidation of C137/C154 of cytoplasmic malate dehydrogenase (MDHC) in HCR. In both Overmyer et al. [28] and Souza et al. [29] the post-translation modification of malate dehydrogenase isoforms were associated with greater enzymatic activity, which is consistent with a greater capacity to exchange reducing equivalents via the malate-aspartate shuttle in HCR skeletal muscle. These findings are consistent with human muscle responses to exercise in diabetic patients, which also included gains in the abundance of enzymes of the malate-aspartate shuttle [30]. Overall, the recent proteomic analyses of mitochondria-enriched muscle fractions suggest adaptations to aerobic training are more intricate than a general upward shift in muscle mitochondrial content.