4-Hydroxybutyric aciduria
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The molecular defect in 4-hydroxybutyric aciduria is in the enzyme succinic semialdehyde hydrogenase (EC 1.2.1.2) (see Figure 13.1) [5, 27, 28]. Succinic semialdehyde is the product of the transamination of GABA and is normally converted to succinic acid. When succinic semialdehyde accumulates, it is alternatively reduced to 4-hydroxybutyric acid. The enzyme is active in lymphocytes freshly isolated from peripheral blood and in cultured lymphoblasts [5, 21, 27, 28]. Accumulation of labeled succinic semialdehyde has been demonstrated in patients’ lymphocytes following incubation with 14C-labeled GABA, and there was no evidence of further metabolism to succinic acid [5]. Direct assay of the enzyme with 14C-labeled succinic semialdehyde yielded activity that approximated 4 percent of the control level in one patient [27] and was undetectable in another. In another [20], it was as high as 21 percent in lymphocytes.
Dietary Substances Not Required in Human Metabolism
Luke Bucci in Nutrients as Ergogenic Aids for Sports and Exercise, 2020
Succinic acid is a component of the Krebs cycle, and as such is added to several dietary supplements with accompanying claims of ergogenesis. Only one report of succinate on exercise performance was found.913 Fasted male mice (serving as their own controls) were fed 0,30, or 300 mg/kg sodium succinate, and swim tests to exhaustion started at 30, 60, and 120 min post-feeding. The only group to show improvement in swim times was the 300 mg/kg group 2 h after feeding (455 vs. 389 sec). Retesting of swim times 3 h after initial swim tests revealed no effects of succinate. Chronic feeding (7 d of 20 mg/ml succinate in drinking water) did not affect swim times. Results suggested that large doses of sodium succinate may improve exercise performance in swimming mice under certain conditions, and that extrapolation to humans would indicate that huge doses of succinate need to be studied for a possible ergogenic effect. No guidelines in humans for succinate supplementation exist at this time.
Bacterial vaginosis in pregnancy: Evidence-based approaches
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Biophysical changes associated with bacterial vaginosis include elevated pH (>4.5), reduced redox potential, increased fluid concentrations of diamines, polyamines, and organic acids, as well as increased concentrations of enzymes, including mucinases, sialidases, IgA proteases, collagenases, nonspecific proteases, and phospholipases A2 and C (24,33–39). Endotoxin (lipopolysaccharide), cytokine interleukin-1a, and prostaglandins E2 and F2a are also increased in the vaginal fluid of women with bacterial vaginosis (40,41). Amines, primarily trimethyla-mine, putrescine, and cadaverine, are produced during amino acid metabolism by bacterial vaginosis–associated anaerobic bacteria (37,42). These volatile amines are released as pH increases and are responsible for the “sharp” or “fishy” odor sometimes noticed in the presence of bacterial vaginosis (37,43). Several short-chain fatty acids, including succinate, acetate, propionate, isobutyrate, butyrate, and isovalerate, are also increased in bacterial vaginosis (24). In vitro studies demonstrate that increased succinic acid dramatically impairs neutrophil phagocytic killing, response to chemotactic stimuli, and generation of respiratory bursts required for bacterial killing (44). Butyrate inhibits lymphocyte activation by release of an endotoxin (45,46).
Succinic acid inhibits the activity of cytochrome P450 (CYP450) enzymes
Published in Pharmaceutical Biology, 2020
Hao Wang, Bingyan Xia, Mei Lin, Yongpeng Wang, Bin Sun, Yuzhu Li
Succinic acid (≥98%) and testosterone (≥98%) were obtained from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). The chemical structure of succinic acid is shown in Figure 1. d-Glucose-6-phosphate, glucose-6-phosphate dehydrogenase, corticosterone (≥98%), NADP+, phenacetin (≥98%), acetaminophen (≥98%), 4-hydroxymephenytoin (≥98%), 7-hydroxycoumarin (≥98%), 4′-hydroxydiclofenac (≥98%), sulfaphenazole (≥98%), quinidine (≥98%), tranylcypromine (≥98%), chlorzoxazone (≥98%), 6-hydroxychlorzoxazone (≥98%), paclitaxel (≥98%), 6β-hydroxytestosterone (≥98%), clomethiazole (≥98%), and furafylline (≥98%) were obtained from Sigma Chemical Co (MO, USA). Montelukast (≥98%) was obtained from Beijing Aleznova Pharmaceutical (Beijing, China). Coumarin (≥98%), diclofenac (≥98%), dextromethorphan (≥98%), and ketoconazole (≥98%) were purchased from ICN Biomedicals (Costa Mesa, California). Pooled HLMs were purchased from BD Biosciences Discovery Labware. All other reagents and solvents were of analytical reagent grade.
Pharmacokinetic study on the interaction between succinic acid and irbesartan in rats and its potential mechanism
Published in Pharmaceutical Biology, 2021
Yongpeng Wang, Ruping Rui, Xiaoyan Zhang, Bin Sun
The combination of diverse drugs or herbs is a common therapeutic strategy in the treatment of cardiovascular disease, especially in the use of traditional Chinese medicine (Parvez and Rishi 2019). The co-administration of different drugs could offer potential advantages, such as increasing efficacy and improving patient compliance, but it also brings adverse effects, such as therapy failure and toxicity (Rekić et al. 2017). Succinic acid is a major extraction of amber, which is commonly used in the therapy of arrhythmia. It has also been reported that succinic acid has various pharmacological effects, such as cardioprotective, antithrombotic, anti-inflammatory, and antibacterial (Tang et al. 2013; Zhang et al. 2014; Nissen et al. 2019). In the previous study, succinic acid has been demonstrated to inhibit the activity of cytochrome P450 enzymes (CYP450s), which are a series of enzymes responsible for the metabolism of a wide range of endogenous compounds (Wang et al. 2020). The activity of CYP450s has been considered as a critical factor that mediates drug-drug interaction during drug co-administration. Therefore, the inhibitory effect of succinic acid implies its potential interaction with other combined drugs.
β-Cyclodextrin-based ternary complexes of haloperidol and organic acids: the effect of organic acids on the drug solubility enhancement
Published in Pharmaceutical Development and Technology, 2018
Prisada Rakkaew, Jiraphong Suksiriworapong, Doungdaw Chantasart
In citrate buffer pH 3, tartaric acid and lactic acid dramatically increased the solubility of HALO (p value < .05). This result was attributed to the higher amount of unionized species of tartaric acid and lactic acid than succinic acid. This species could interact with HALO and β-CD leading to enhanced solubilization capacity. Although succinic acid (pKa 4.2 and 5.6) had the highest amount of unionized species of acid at this pH, the solubility of HALO/β-CD/succinic acid ternary complex was the lowest (13.19 ± 0.19 mM) when compared with other acids because of the lack of hydroxyl groups for hydrogen bond formation and the unsuitable conformation of the acid (Fenyvesi et al. 1999; Csernák et al. 2005). The KC and CE values of the ternary complexes are shown in Table 1. In citrate buffer pH 3 and 6, the KC value of all ternary complexes was significantly different (p value < .05). The highest KC and CE values were obtained by the ternary complexes with lactic acid followed by tartaric acid and succinic acid, respectively. The ternary complexes with succinic acid showed the lowest KC and CE values in both media, indicating the weak interaction among acid, drug, and β-CD (Pascal et al. 2005).
Related Knowledge Centers
- Dicarboxylic Acid
- Electron Transport Chain
- Fumaric Acid
- Metabolic Intermediate
- Succinate Dehydrogenase
- Citric Acid Cycle
- Mitochondrion
- Chemical Formula
- Ion
- Adenosine Triphosphate