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Phenylketonuria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Phenylalanine hydroxylase, the defective enzyme in PKU, has a tetrahydrobiopterin cofactor that is required for the hydroxylation of phenylalanine. In the hydroxylase reaction, a quinonoid dihydrobiopterin is formed. The reduction of this compound to reform tetrahydrobiopterin is catalyzed by dihydropteridine reductase [33, 34]. The quinonoid oxidation product is unstable and, unless it is promptly reduced, it forms the 7, 8-dihydrobiopterin and is no longer a substrate for dihydropteridine reductase, but it can be reduced by dihydrofolate reductase in the presence of the reduced form of nicotinamide-adenosine dinucleotide phosphate (NADPH). The synthesis of biopterin begins with guanosine triphosphate and proceeds through reduced neopterin (α-D-erythro-7, 8-dihydroneopterin triphosphate) to a dihydro-precursor of tetrahydrobiopterin [35, 36].
Herbal Products in Antihypertensive Therapy
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Fernão C. Braga, Steyner F. Côrtes
The antihypertensive effect of ginseng has been investigated by several clinical trials. In a recent study, red Korean ginseng was given to pre-hypertensive subjects (5 g divided into 10 capsules, daily). After 12 weeks, the treated group showed reductions of 6.5 and 5.0 mmHg in systolic and diastolic blood pressure, respectively, in comparison to control. The reduction in blood pressure was associated with decreased lipoprotein-associated phospholipase A2 and lysophosphatidylcholines levels and increased dihydrobiopterin concentration in the treated subjects (Cha et al. 2016). In another study performed with mild hypertensive patients, a P. ginseng extract enriched in ginsenoside protopanaxatriol (300 mg/day) induced a significant decrease of 3.1 and 2.3 mmHg in SBP and DBP, respectively (Rhee et al. 2014). In turn, a P. ginseng extract enriched in ginsenoside Rg3 (400 mg) given to healthy subjects induced a significant reduction in SBP and DBP respectively by 4.8 ± 6.8 and 3.6 ± 6.4 mmHg hours after ingestion (Jovanovski et al. 2014). A clinical trial carried out with hypertensive patients treated with P. quinquefolius (3 g/day, 12 weeks) showed a decrease in SBP by 17.4 mmHg (Mucalo et al. 2013).
A Mechanistic Review of Methotrexate and Celecoxib as a Potential Metronomic Chemotherapy for Oral Squamous Cell Carcinoma
Published in Cancer Investigation, 2023
Mehta Vedant Kamal, Mahadev Rao, Rama Rao Damerla, Ananth Pai, Krishan Sharan, Akhil Palod, Preethi S. Shetty, Nawaz Usman, Naveena A.N. Kumar
Methotrexate was initially developed as a structural analog of folic acid and is being used for cancer treatment, especially for breast, lung, and head and neck cancers (62). Methotrexate hinders folic acid metabolism and ultimately affects the one-carbon metabolism leading to a decrease in the synthesis of purines and pyrimidines leading to arrest in DNA replication and ultimately cell proliferation (Figure 4) (62,63). In addition to catalyzing the reduction of dihydrofolate to tetrahydrofolate, DHFR also catalysis the reduction of dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4); methotrexate inhibits the reduction of both dihydrofolate and BH2 at similar concentrations (Figure 4) (64). All nitric oxide synthases need the cofactor BH4 (a group of enzymes that catalyze the conversion of l-arginine into nitric oxide) (65).
Nutrition-based interventions for mood disorders
Published in Expert Review of Neurotherapeutics, 2021
Lais B Martins, Jenneffer Rayane Braga Tibães, Marsal Sanches, Felice Jacka, Michael Berk, Antônio L Teixeira
Inflammation can influence the production of neurotransmitters traditionally implicated in the regulation of emotion, mainly serotonin and dopamine. Pro-inflammatory cytokines can decrease serotonin availability through the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) which catabolizes tryptophan, an essential amino acid necessary for the synthesis of serotonin, into kynurenine [28,29]. For example, treatment with interferon-α (IFN-α) induces depressive symptoms in association with changes in peripheral and central kynurenine levels [30]. Immune activation also increases the activity of the enzyme GTP-cyclohydrolase 1 (GTP-CH1) which catalyzes the conversion of guanosine-triphosphate (GTP) into dihydrobiopterin (BH2). BH2 is in turn converted into neopterin at the expense of tetrahydrobiopterin (BH4) production. An increase in neopterin levels means a reduction in the bioavailability of BH4, which participates in serotonin and dopamine synthesis [28]. The increase in neopterin levels in MDD has been positively associated with the number of depressive episodes [31].
Pathobiology of ischiocavernosus and bulbospongiosus muscles in long-term diabetic male rats and its implication on erectile dysfunction
Published in The Aging Male, 2020
Prakash Seppan, Ibrahim Muhammed, Zafar Iqbal Khan Mohammad, Sathya Bharathy Sathyanathan
The high level of circulatory glucose induces high oxidative stress and their secondary cascades in multifaceted mechanism induce muscle degeneration in diabetic rats. The influenced by hyperglycemia can greatly enhance the formation of peroxynitrite in tissue causing tetrahydrobiopterin (BH4) oxidization (a NOS III cofactor to dihydrobiopterin) [52,53]. With BH4 deficiency, the NOS III is in an uncoupled state, which means that the electrons flowing from NOS III reductase domain to the oxygenase domain are diverted to molecular oxygen rather than to L-arginine resulting in production of superoxide rather than NO [54–56].