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.
LIVER METABOLISM
David M. Gibson, Robert A. Harris in Metabolic Regulation in Mammals, 2001
Ammonia generated by transamination followed by oxidative deamination of gluta mate enters the urea cycle by condensing with carbon dioxide and 2ATPs to give car bainovi phosphate. The enzyme responsible for this reaction, carbamoyl phospliate synthetase, is heavily dc|>cndcnt upon activation by the allosteric effector N-acctylglutamate, produced bv N-acctylglutamate synthase (Figure 8.9). Without N-acetylglutamate, carlxamovl phosphate synthetase is practically inert. N-acctylglutamate synthase is subject to regulation by the availability of glutamate as a substrate and by the level of arginine as a positive allosteric effector. Consumption of a meal rich in protein increases the amount of glutamate and arginine presented to the liver, which in turn promotes N-acetvlglutamate synthesis and the downstream enhance ment of carbamoyl phosphate synthesis and urea synthesis. Several enzymes of the urea cycle, especially carbamoyl phosphate synthetase and ornithine transcarbamoylase, are also induced in response to high dietary protein. Glucagon, released from «-cells of the pancreas in response to amino acids, is the major circulating messenger responsible lor increased expression of urea cycle enzymes in response to high dietary protein.
Nutrient Metabolism and Fetal Brain Development
Emilio Herrera, Robert H. Knopp in Perinatal Biochemistry, 2020
In the fetal brain, amino acids are utilized for biosynthesis of purines, pyrimidines, and polyamines. The de novo pathway for pyrimidine biosynthesis is summarized in Figure 3 and begins with the combination of nitrogen from glutamine with bicarbonate, a reaction catalyzed by carbamyl phosphate synthetase. Carbamyl phosphate is converted to carbamyl aspartate and dihydro orotic acid. The capacity for glutamine synthesis in the fetal brain and the low KM for glutamine make the synthesis of carbamyl phosphate an effective means for reutilizing ammonia derived from maternal gluconeogenesis or transamination of branched-chain amino acids.14 The de novo pathway for purine biosynthesis also fixes nitrogen that is spared from urea synthesis.
Citrulline Malate Fails to Improve German Volume Training Performance in Healthy Young Men and Women
Published in Journal of Dietary Supplements, 2020
Andrew J. Chappell, Daniel M. Allwood, Trevor N. Simper
Citrulline (CIT) is a nonessential amino acid that acts as a nitrogen ion acceptor from carbamoyl-phosphate within the urea cycle. The dietary supplement citrulline malate (CM) has been purported to improve aerobic and anaerobic exercise performance via a variety of mechanisms, including improved ammonia, arginine, and lactic acid metabolism, alongside an increase in adenosine triphosphate (ATP) production (da Silva et al. 2017). Increasing muscle CIT may attenuate ammonia accumulation resulting in a lactic acid buffer effect, which might enhance subsequent recovery, attenuate fatigue, and reduce postexercise muscle soreness (Ochiai et al. 2012; Cutrufello et al. 2015). Ammonia influences fatigue by stimulating phosphofructokinase, leading to an increased rate of glycolysis (Takeda et al. 2011). This may increase blood lactic acid during exercise, inhibiting pyruvate oxidation, leading to hydrogen ion accumulation and a reduction in muscle pH and contractile potential (Cutrufello et al. 2015).
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).
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.
Related Knowledge Centers
- Ammonia
- Bicarbonate
- Citrulline
- Ornithine
- Pyrimidine
- Sirtuin
- Urea Cycle
- Nitrogen
- Ion
- Ornithine Transcarbamylase