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Toxins in Neuro-Ophthalmology
Published in Vivek Lal, A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
Nitrous oxide is an anesthetic agent and is popular as a recreational drug due to its euphoric properties and availability as a so-called “legal high.” It is usually inhaled from balloons filled from “whippits” (small, pressurized canisters of N2O used in whipped cream dispensers). It irreversibly binds, oxidizes, inactivates and depletes vitamin B12. B12 inactivation further leads to depletion of methionine and accumulation of homocysteine as it is an essential cofactor for methionine synthase. Neurologically, B12 depletion results in demyelination leading to myelopathy, neuropathy, myeloneuropathy, cognitive changes and optic nerve toxicity. Ocular symptoms will be similar to B12 deficiency due to other causes. The visual loss is symmetric, painless and progressive. Central and centrocecal scotomas are the rule, and the optic disc will be normal in the early stages of the condition. Vision recovered usually with intramuscular injections of hydroxocobalamin unless optic atrophy becomes well established.
Nutritional Diseases
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Chelsea Kesty, Madeline Hooper, Erin McClure, Emily Chea, Cynthia Bartus
Definition: This is an essential cofactor for methionine synthase and plays an important role in DNA synthesis. Vitamin B12 deficiency is characterized by neurologic, hematologic, and psychiatric findings.
Nutritional Deficiencies
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Deepa Bhupali, Fernando D. Testai
Dietary folate exists predominantly as polyglutamates. These are hydrolyzed to monoglutamates and absorbed in the jejunum. Folate circulates in the blood mainly as 5-methyltetrahydrofolate (5-methyl-THF), which is absorbed by most cells. 5-Methyl-THF and methylcobalamin are cofactors of the methionine synthase and are required for the conversion of homocysteine to methionine (Figure 10.9). Folate is involved in genomic and nongenomic methylation processes. Its deficiency affects, primarily, the production of DNA and RNA as well as the metabolism of amino acids. Folate deficiency is seen in the following circumstances: Alcoholism.Malabsorption.Impaired folate metabolism: Methotrexate.Anticonvulsants (phenobarbital, phenytoin, valproic acid, and carbamazepine).Antimalarials.
Cobalamin and folic acid deficiencies presenting with features of a thrombotic microangiopathy: a case series
Published in Acta Clinica Belgica, 2022
Britt Ceuleers, Sofie Stappers, Jan Lemmens, Lynn Rutsaert
Folic acid plays a key role in the conversion of homocysteine to methionine via the vitamin B-12–dependent methionine synthase reaction. Impairment of this process, as seen in vitamin B12- and folic acid deficiency, is associated with hyperhomocysteinemia and compromised DNA synthesis [4]. This last-mentioned consequence introduces ineffective erythropoiesis, implicating intramedullary destruction of the abnormal and fragile erythroid cell precursors. Biochemically, this manifests as a megaloblastic macrocytic anemia with elevated lactate dehydrogenase and indirect bilirubin levels, sometimes accompanied by a slight decrease in haptoglobin levels in the serum [5–7]. Additionally, ineffective erythropoiesis may present with iron overload secondary to inappropriately increased intestinal iron absorption via suppression of hepcidin [8,9].
A narrative review on the role of folate-mediated one-carbon metabolism and its associated gene polymorphisms in posing risk to preeclampsia
Published in Clinical and Experimental Hypertension, 2021
Sadia Mahmood, Hooria Younas, Amna Younus, Sammar Nathenial
According to the cellular needs, methylene-THF can be converted to 5-methyl THF by a crucial enzyme called methylenetetrahydrofolate reductase (MTHFR). Further, the folate cycle is linked with the methionine cycle in a way when mTHF donates its carbon to homocysteine it generates methionine which is important for protein synthesis and is required for normal growth (30). Thus, the bicyclic pathways collectively circulate one carbon units. Methionine can form S-adenosylmethionine (SAM) using methionine adenyltransferase, SAM is a substrate for methyltransferases, and the enzyme is needed for methylation of DNA, RNA, lipids, and proteins. Additionally, SAM is also used for the synthesis of polyamines that regulates various biological processes. After SAM has donated the methyl group, it is converted to S-adenosylhomocysteine (SAH) which can further be hydrolyzed to homocysteine and adenosine. Again, methionine can be regenerated by methionine synthase (MTR) which requires vitamin B12 (cobalamin) to perform its function. MTR becomes inactive due to its co-factor oxidation after undergoing the reaction. Hence, another enzyme called methionine synthase reductase (MTRR) carries out reductive remethylation of methionine synthase to maintain the enzyme in its active form (31–33).
Evaluation of methylenetetrahydrofolate reductase (MTHFR) activity and the levels of homocysteine and malondialdehyde (MDA) in the serum of women with preeclampsia
Published in Clinical and Experimental Hypertension, 2020
Sahar Mazloomi, Shohreh Alimohammadi, Iraj Khodadadi, Tayebeh Ghiasvand, Gholamreza Shafiee
Significant relationship between homocysteine levels and MTHFR enzymatic activity in two groups of women with normal and preeclampsia showed that there was no linear relationship between the two variables. It means that with increasing MTHFR activity, the amount of homocysteine decreases. In other words, there is an inverse relationship between enzyme activity and homocysteine levels, which is obvious with respect to the mechanism of action of the enzyme and homocysteine. These findings are consistent with previous studies (21) and it seems that due to the biochemical mechanism of homocysteine in the body, it was regulated by the activity of other enzymes such as methionine synthase, which is another key enzyme in the pathway of conversion of homocysteine to methionine. Also, the role of vitamin B12, a coenzyme, as a carrier of single carbonyl form of methylenetetrahydrofolate on homocysteine may be due to defective factors in patients with preeclampsia and resulting in the accumulation of homocysteine rather than consuming and reducing its damage. Finally, these findings are consistent with results from previous studies showing that increased homocysteine in individuals have preeclampsia due to increased MDA in these individuals compared to controls (28) and may be due to the oxidative destructive effects in arteries (29).