Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Succinylacetone (SA) (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumaryl acetoacetate hydrolase activity. Patients with this disease are associated with a number of abnormalities, including aminoaciduria, proteinuria, liver failure, commonly hepatoma, and decreased GSH concentration in the liver. In the course of our studies of tyrosinemia, we found that the urine of patients with this disorder contains material(s) that absorbs light at 315 nm. We investigated the nature of the 315 nm material in detail. SA was found to react with amino acids and protein nonenzymatically, to form stable adducts at physiological temperature and pH. All SA adducts with amino acids and/or proteins exhibited an absorption peak at 315 nm. Although all amino acids reacted with SA, the most reactive amino acid was lysine (Lys), followed, in order, by glycine, methionine, phenylalanine, serine, alanine, and glutamine. SA-adducts were unstable at pH below 6, while they were made considerably more stable after reduction with NaBH4, suggesting that SA forms an adduct via Schiff base formation. High-performance liquid chromatography (HPLC) analysis of urines from patients with tyrosinemia revealed the existence of SA-glycine, SA-methionine, SA-tyrosine, and SA-phenylalanine. After digestion of urines with proteinase K, three more HPLC peaks appeared, which all corresponded to SA-Lys adducts. TLC analysis of SA-Lys showed that SA-Lys could form as many as seven different adducts. No SA-adduct peaks were observed in HPLC in urines from normal subjects, patients with other forms of aminoaciduria, or patients with the nephrotic syndrome. In addition to amino acids and proteins, SA reacted with reduced glutathione (GSH) and formed a stable adduct. These findings suggest that SA adduct formation with amino acids, GSH, and proteins is a significant process occurring in tyrosinemia, and may account for certain of the pathologic findings in this hereditary disorder.
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PMID:Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts. 392 1

ANCA-associated vasculitis (AAV) is a rare, but potentially severe autoimmune disease, even nowadays displaying increased mortality and morbidity. Finding early biomarkers of activity and prognosis is thus very important. Small extracellular vesicles (EVs) isolated from urine can be considered as a non-invasive source of biomarkers. We evaluated several protocols for urinary EV isolation. To eliminate contaminating non-vesicular proteins due to AAV associated proteinuria we used proteinase K treatment. We investigated the differences in proteomes of small EVs of patients with AAV compared to healthy controls by label-free LC-MS/MS. In parallel, we performed an analogous proteomic analysis of urine samples from identical patients. The study results showed significant differences and similarities in both EV and urine proteome, the latter one being highly affected by proteinuria. Using bioinformatics tools we explored differentially changed proteins and their related pathways with a focus on the pathophysiology of AAV. Our findings indicate significant regulation of Golgi enzymes, such as MAN1A1, which can be involved in T cell activation by N-glycans glycosylation and may thus play a key role in pathogenesis and diagnosis of AAV. SIGNIFICANCE: The present study explores for the first time the changes in proteomes of small extracellular vesicles and urine of patients with renal ANCA-associated vasculitis compared to healthy controls by label-free LC-MS/MS. Isolation of vesicles from proteinuric urine samples has been modified to minimize contamination by plasma proteins and to reduce co-isolation of extraluminal proteins. Differentially changed proteins and their related pathways with a role in the pathophysiology of AAV were described and discussed. The results could be helpful for the research of potential biomarkers in renal vasculitis associated with ANCA.
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PMID:Mass spectrometry-based proteomic exploration of the small urinary extracellular vesicles in ANCA-associated vasculitis in comparison with total urine. 3330 52