Structure, Function and Evolutionary Aspects of Mitochondria
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Mitochondrial matrix contains a wide variety of metabolites. Pyruvate, acetyl CoA, acyl CoA, α-ketoglutarate, isocitrate, succinyl CoA, succinate, malate, fumarate and oxaloacetate are involved in citric acid cycle. L-citrulline, L-ornithine and carbamoyl phosphate are used in urea cycle. Mitochondria DNA, RNA and transfer RNA are used for protein synthesis. Another ions like Ca+2, K+, Mg+2 are also present in the matrix. Moreover CO2, H2O, O2, ATP, ADP and inorganic phosphate are present as metabolites. Enzymes like citrate synthase, Pyruvate dehydrogenase, isocitrate dehydrogenase, aconitase, α-ketoglutarate dehydrogenase, succinyl CoA synthetase, fumerase and malate dehydrogenase facilitates the TCA cycle. Transaminase facilitates amino acid production. β-oxidation uses pyruvate carboxylase, acyl CoA dehydrogenase and β-ketothiolase. The urea cycle is facilitated by carbamoyl phosphate synthetase I and ornithine transcarboxylase.
Metabolism of Glutamine and Glutamate in the Liver — Regulation and Physiological Significance
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
Gebhardt and Mecke82,83 studied the distribution of glutamine synthetase in liver parenchyma using an immunofluorescence technique. This enzyme was found to be localized exclusively in cells in the perivenous region. In contrast, carbamoyl phosphate synthase is located in the periportal region.84 These and later related observations77 of other enzymes indicated heterogeneity in glutamine metabolism with urea synthesis and probably glutamine degradation occurring in the periportal cells and glutamine synthesis occurring in the perivenous region. This picture was also consistent with biochemical findings. Allylformate damages the periportal areas of the liver selectively while carbon tetrachloride destroys mainly the perivenous region. Administration of allylformate decreased the activities of the urea cycle enzymes but had no effect on that of glutamine synthetase while carbon tetrachloride strongly decreased glutamine synthetase but had no effect on enzymes of the urea cycle.83 In the perfused liver from animals pretreated with carbon tetrachloride, glutamine synthesis from added ammonia was greatly impaired while urea synthesis was unaffected.85 However, due to the difficulties discussed above in the isolation of liver glutaminase and the failure of antisera to glutaminases from other tissues to crossreact with the liver enzyme, it so far has not been possible to apply immunofluorescence techniques to detect the location of liver glutaminase.
The Genetic Basis of NEC Susceptibility
David J. Hackam in Necrotizing Enterocolitis, 2021
Arginine is an important substrate for NO, a potent vasodilator that regulates mucosal blood flow and helps maintain mucosal integrity. Low arginine levels have been implicated in NEC based on observational studies demonstrating hypoarginemia in preterm infants with NEC and clinical trials showing decreased NEC in infants following arginine supplementation (58–60). Moonen et al. (61) evaluated C to A nucleotide transversion (T1405N) of carbamoyl-phosphate synthase (CPS), which is functionally correlated with low plasma arginine levels, in a small study of 51 preterm infants (17 with NEC). They found that the CC genotype was associated with increased NEC, although this association was not significant once adjusted for gestational age and birth weight. As a follow-up to this study, Moonen et al. (62) prospectively recruited 477 preterm infants and investigated the same CPS1 polymorphism in NEC. They found no significant association between CC genotype and NEC. Instead, a significant negative association was found between the minor A-allele and the combined outcome of NEC or death, suggesting that the A-allele variant may confer protection against NEC.
Porphyromonas gingivalis diffusible signaling molecules enhance Fusobacterium nucleatum biofilm formation via gene expression modulation
Published in Journal of Oral Microbiology, 2023
Yukiko Yamaguchi-Kuroda, Yuichiro Kikuchi, Eitoyo Kokubu, Kazuyuki Ishihara
Eighty-seven genes were downregulated (Table 2), including those encoding protein involved in de novo synthesis of purine (phosphoribosyl amine-glucine ligase, purH, class I SAM-dependent methyltransferase, phosphoribosyl glycinamide formyl transferase, purM, amidophosphoribosyltransferase, phosphoribosylaminoimidazole-succinocarboxamide synthase, purE, and phosphoribosylformylglycinamidine synthetase), proteins involved in de novo pyrimidine synthesis (bifunctional pyr operon transcriptional regulator/uracil phosphoribosyltransferase PyrR, aspartate carbamoyltransferase, dihydroorotase, glutamine-hydrolyzing carbamoyl-phosphate synthase small subunit, carbamoyl-phosphate synthase large subunit, dihydroorotate dehydrogenase electron transfer subunit, dihydroorotate dehydrogenase, orotidine 5’-phosphate decarboxylase, and orotate phosphoribosyltransferase), bioA involved in biotin metabolism, and TonB-dependent receptor.
Fermented whey modulated AFB1 and OTA-induced hepatotoxicity and nephrotoxicity in vivo. A relative and absolute quantification about sex differences
Published in Toxicology Mechanisms and Methods, 2023
Massimo Frangiamone, Alexander Yemelin, Alessandra Cimbalo, Guillermina Font, Eckhard Thines, Lara Manyes
For in vivo toxicological studies concerning mycotoxins, a main aspect to take into account is the sex-dependent response. For instance, in mice, chickens, and humans, the liver carcinogenicity of AFB1 is greater in males than in females. Similarly, OTA prompted kidney tumors much more frequently in male rats than in females (Soler and Oswald 2018; EFSA 2020a; EFSA 2020b). The beneficial effects of probiotics have been also reported to show sex-related responses (He et al. 2019; Myles et al. 2020). Furthermore, the findings achieved with animal models can be extrapolated to humans by using biological biomarkers (Kraus 2018). In this sense, carbamoyl phosphate synthetase-1 (CPS1), the most abundant protein in liver mitochondria, represents a robust biomarker to detect hepatic diseases in humans and rats (Weerasinghe et al. 2014). Likewise, kidney injury molecule 1 (KIM-1) has been accepted by the Food and Drug Administration and European Medicines Agency as a highly sensitive and specific biomarker to monitor chemical-induced kidney injury in preclinical studies (Griffin et al. 2019).
Novel considerations on drug safety in epilepsy
Published in Expert Opinion on Drug Safety, 2021
Various genes have also been identified which are associated with some of the more severe adverse effects of valproate. The T1405 polymorphism variant in the carbamoyl phosphate synthetase 1 (CPS1) was found to be a significant risk factor for the occurrence of hyperammonemia with valproate.A retrospective study in Japanese patients showed that the Val16Ala polymorphism of the Superoxide Dismutase2 (SOD2) gene has an impact on the relationship between valproate exposure and GT elevation [13].Weight gain, a common adverse reaction of valproate, has been associated with leptin receptor (LEPR) and ankyrin repeat kinase domain containing 1 (ANKK1) gene polymorphisms in a cohort of Han Chinese people with epilepsy.In a pediatric cohort, it was found that CYP2C9 variant-guided treatment significantly reduced valproate misdosing [13].
Related Knowledge Centers
- Adenosine Diphosphate
- Ammonia
- Bicarbonate
- Biosynthesis
- Carbamic Acid
- Carbamoyl Phosphate
- Glutamine
- Pyrimidine
- Arginine
- Adenosine Triphosphate