RESUMO
MitoNEET is a [2Fe-2S] redox active mitochondrial protein belonging to the CDGSH iron-sulfur domain (CISD) family of proteins. MitoNEET has been implicated as a potential target for drug development to treat various disorders, including type-2 diabetes, cancer, and Parkinson's disease. However, the specific cellular function(s) for mitoNEET still remains to be fully elucidated, and this presents a significant roadblock in rational drug development. Here, we show that mitoNEET binds the enzymatic cofactor pyridoxal phosphate (PLP) specifically at only one of its 11 lysine residues, Lys55. Lys55 is part of the soluble portion of the protein and is in a hydrogen-bonding network with the histidine residue that ligates the [2Fe-2S] cluster. In the presence of mitoNEET, PLP catalyzes the transamination reaction of the amino acid cysteine and the alpha-keto acid 2-oxoglutarate to form 3-mercaptopyruvate and glutamate. This work identifies, for the first time, mitoNEET as an enzyme with cysteine transaminase activity.
Assuntos
Proteínas Ferro-Enxofre , Proteínas Ferro-Enxofre/química , Fosfato de Piridoxal/metabolismo , Histidina , Cisteína , Transaminases/metabolismo , Ácidos Cetoglutáricos , Lisina , Proteínas Mitocondriais/metabolismo , Ferro/metabolismo , Enxofre , Glutamatos , Hidrogênio/metabolismoRESUMO
INTRODUCTION: Some systemic diseases have ophthalmic manifestations. Findings on examination of the fundus can assist in the diagnosis and treatment of these diseases. In this manuscript, we present two ophthalmic conditions that cause optic disc edema and are highly associated with obstructive sleep apnea (OSA). The conditions are non-arteritic anterior ischemic optic neuropathy (NAION), and Papilledema associated with the Pickwickian syndrome. When these conditions are suspected, the patient should be referred for a polysomnography examination.
