Isoniazid
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Neurotoxicity is due to the effects of isoniazid on the vitamin B6 group (pyridoxine) metabolism. The B6 group is rapidly converted in the body to the coenzymes pyridoxal phosphate and pyridoxamine phosphate, which are essential for protein metabolism. Vitamin B6 is also a cofactor in the production of amines, which act as synaptic transmitters in various brain areas, and it is also necessary for the formation of the inhibitory transmitter gamma-aminobutyric acid (Snider, 1980). Isoniazid can cause vitamin B6 deficiency by the formation of hydrazones, which inhibit the conversion of pyridoxine to pyridoxal phosphate and which also inactivate the latter. Isoniazid has a further action of lowering effective tissue and serum levels of pyridoxine through the formation of these isoniazid–pyridoxine hydrazones, which are rapidly excreted by the kidney (Miller et al., 1980; Atkins, 1982).
The Role of Nutraceuticals in Gestational Diabetes Mellitus
Priyanka Bhatt, Maryam Sadat Miraghajani, Sarvadaman Pathak, Yashwant Pathak in Nutraceuticals for Prenatal, Maternal and Offspring’s Nutritional Health, 2019
Pyridoxine or vitamin B6 is found generally in foods and can be used as a dietary supplement to increase dietary intake or partially reduce disease risk (53). Some clinical examinations have indicated far-reaching beneficial effects of using pyridoxine in the prevention or amelioration of GDM. Early studies showed that blood concentration of vitamin B6 is significantly decreased in diabetic animals and patients54–57. Bennink and colleagues demonstrated that pregnant women with GDM who were treated with vitamin B6 (pyridoxine), 100 mg/day for two weeks, improved oral glucose tolerance considerably (58). Vitamin B6 deficiency is found to reduce circulating insulin levels and has been related to degenerative changes in pancreatic β-cells (59, 60). Beyond that, the health benefits of pyridoxamine (amine form of vitamin B6) can be attributed to the inhibition of the production of oxidative stress markers or scavenging the reactive oxygen species (61). There seems to be an increased requirement/utilization of vitamin B6 in GDM, accordingly various studies are needed to reach a definitive and overall conclusion regarding adjuvant therapy of vitamin B6 in the prevention of GDM complications.
Vitamin B6 and Other Inhibitors of Glucocorticoid Receptor Function and Cell Death of B16 Melanoma Cells
Maryce M. Jacobs in Vitamins and Minerals in the Prevention and Treatment of Cancer, 2018
In vitro experiments showed that pyridoxal phosphate inhibited the interaction of activated transformed glucocorticoid receptor with DNA.6 This was not a consequence of interaction of the vitamer with DNA but rather directly with the receptor.6 Further experiments showed that a lysine residue at or near the steroid binding domain was also a target and these two sites could be studied independently by virtue of different temperature dependencies.9 In contrast to pyridoxal phosphate, pyridoxine, pyridoxamine and pyridoxamine phosphate were without activity while pyridoxal had only partial activity.6 Later experiments showed that a non-specific aldehyde had very low activity indicating that the activity of pyridoxal phosphate was specific.
Vitamin B-6 and depressive symptomatology, over time, in older Latino adults
Published in Nutritional Neuroscience, 2019
Sandra P. Arévalo, Tammy M. Scott, Luis M. Falcón, Katherine L. Tucker
Vitamin B-6 is a water-soluble compound that comprises three different pyridine derivatives, pyridoxine, pyridoxal, and pyridoxamine, of which PLP is the biologically most active form.19 The coenzyme PLP is an essential cofactor for amino acid decarboxylases involved in the synthesis of neurotransmitters implicated in depression, including dopamine, norepinephrine, serotonin or 5-hydroxytryptamine (5-HT), and γ-amino butyric acid (GABA).20,21 Immune dysregulation and activation of the inflammatory response system are also characteristic of major depression.22 The role of vitamin B-6 in the metabolism of tryptophan and one-carbon metabolism makes vitamin B-6 a relevant cofactor in the body’s immune response.20 Vitamin B-6 prevents the accumulation of neurotoxic intermediates produced during tryptophan metabolism, acting as a cofactor in the metabolism of tryptophan through the kynurenine aminotransferase and kynureninase enzymes.23 Several epidemiological and treatment studies have established an association between low vitamin B-6 status and depressive symptomatology. However, research gaps in the current vitamin B-6 and depression association include the cross-sectional design of the majority of current investigations, the failure to control for relevant confounders, and the dearth of studies examining this association in ethnically diverse populations at high risk for depressive symptomatology.24
Interference of altered plasma trace elements profile with hyperhomocysteinemia and oxidative stress damage to insulin secretion dysfunction in Psammomys obesus: focus on the selenium
Published in Archives of Physiology and Biochemistry, 2023
Asma Bouazza, Eric Fontaine, Xavier Leverve, Elhadj-Ahmed Koceir
Concerning the relationship between vitamin B group in diet and HhCys, it seems that no deficiency of pyridoxine (B6), cobalamin (B12) or folic acid (B9), because the LCD and ND contains them, but much more a cellular bioavailability lack, which explains the low plasma vitamins levels (our data). Indeed, HhCys observed in diabetic’s P. obesus (Groups III and IV) can be to explain by the transulfurization pathway (cystathionine synthase reaction) and in the glutathione production (via glutathione synthase reaction) where the pyridoxine is involved. Several studies have shown that the liver is the main organ responsible for the pyridoxine metabolism and provides the active form (phosphorylated form) via a pyridoxine kinase (dependent on Zn and ATP) to pyridoxamine-5-phosphate. ATP serves as a source for the phosphate group (Merrill Jr. and Henderson 1990). In the present study, we observed a decrease in plasma Zn levels in groups III and IV versus the control group. This is related to the diabetes course, where the ATP hepatic production is greatly reduced (Schmid et al. 2011). Besides, our previous data has shown that ATP levels are decreased in diabetic’s P. obesus, which are linked to mitochondrial dysfunction (Bouderba et al. 2012, Gouaref et al. 2017). From the above, the combined deficiency of ATP and Zn demonstrates the accumulation of hCys in the blood and therefore HhCys in diabetic’s P. obesus. This result also explains the depletion of glutathione plasma levels observed in groups III and IV.
Unravelling the genetic architecture of autosomal recessive epilepsy in the genomic era
Published in Journal of Neurogenetics, 2018
Jeffrey D. Calhoun, Gemma L. Carvill
The first neonatal-onset genes with AR inheritance to be implicated in epilepsy, ALDH7A1 and PNPO, encode metabolic enzymes, and are part of the larger group of disorders known as inborn errors of metabolism (IEM) (Table 1). ALDH7A1 variants were discovered in pediatric patients with PDE (Mills et al., 2006). PDE is characterized by seizures refractory to anticonvulsants but responsive to pyridoxine administration (Mills et al., 2010). Antiquitin, encoded by ALDH7A1, is an aldehyde dehydrogenase in the cerebral lysine degradation pathway (Fong, Cheng, & Tang, 2006). Recently, Crispr/Cas9 gene editing was used to generate a zebrafish model of PDE with loss of aldh7a1 expression (Pena et al., 2017). aldh7a1-null zebrafish exhibit characteristic phenotypes including spontaneous seizures, abnormal epileptiform activity, and early lethality. Similar to patients with this disorder, supplementation with pyridoxine or pyridoxal 5′-phosphate resulted in prevention of seizure-like behavior and extended lifespan in this animal model. PNPO variants were first identified in neonatal epileptic encephalopathy patients with reduced activity of enzymes dependent on pyridoxal phosphate (PLP) (Mills et al., 2005). Importantly, these patients’ seizures abate in response to administration of PLP, but not pyridoxine (Mills et al., 2014). Pyridoxine-5-prime-phosphate oxidase, encoded by PNPO, catalyzes the conversion of pyridoxine and pyridoxamine to PLP, the rate-limiting step in vitamin B6 synthesis (Kang et al., 2004; Ngo, LePage, Thanassi, Meisler, & Nutter, 1998).
Related Knowledge Centers
- Chelation
- Methyl Group
- Pyridine
- Pyridoxine
- Scavenger
- Substituent
- Vitamin B6
- Hydroxy Group
- Hydroxymethyl Group
- Radical