Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268318 (ICP)
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Mn is of toxicological concern because overexposure can lead to progressive, permanent neurodegenerative damage. Monomethyl-Mn-pentadienyl-tricarbonyl (MMT) is used as an anti-knock agent in fuel. Exhausted Mn compounds are absorbed in the lung and transported to the liver. Extended exposure causes an overflow of the liver with Mn species moving e.g. to the brain, causing irreversible central nervous system (CNS) disorders like Manganism. This paper focuses on experiments for getting more information on Mn species in liver extracts. The investigations are performed with respect to (1) a size characterization and (2) a subsequent identification of the Mn species in liver extracts using preparative size exclusion chromatography (SEC) followed by capillary zone electrophoresis coupled to inductively coupled plasma mass spectrometry (CZE-ICP-MS). First, extracts were analyzed using a mass calibrated SEC column coupled to ICP-MS detection. The chromatogram showed the 55 Mn-trace and proved main Mn elution between ca. 60-150 kDa. Second, liver extracts were fractionated on the same SEC column, however, now the effluent was directed to a fraction collector. This resulted in fractions containing pre-purified, size characterized Mn species per fraction. It turned out that the Mn concentrations per fraction reflected roughly the previous on-line Mn trace. Third, the fractions were subject to CZE-ICP-MS, where the MS was operated additionally with dynamic reaction cell (DRC) technique. From size characterization (with SEC coupled on-line to ICP-MS or connected to a fraction collector and subsequent Mn determination in fractions) it was shown that most Mn species from liver extract were of high molecular mass (HMM) nature as they eluted mostly between 50 and 80 min, corresponding to ca. 60-150 kDa. With the two-dimensional speciation approach employing first SEC and then CZE-ICP-DRC-MS together with standard addition method, a series of Mn species was identified. Mn species predominantly were Mn-enzymes e.g. arginase, isocitric dehydrogenase, galactosyltransferase, prolidase, pyruvate carboxylase and oxalate oxidase. A typical Mn-transporter--Mn-albumin-- was also seen, whilst Mn-transferrin obviously was degraded during SEC separation. This Mn-compound (independent whether as a standard or from liver extract) was not stable during SEC even at the finally chosen physiological conditions.
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PMID:Analysis of size characterized manganese species from liver extracts using capillary zone electrophoresis coupled to inductively coupled plasma mass spectrometry (CZE-ICP-MS). 1772 21

Human prolidase, the enzyme responsible for the hydrolysis of the Xaa-Pro/Hyp peptide bonds, is a key player in the recycling of imino acids during the final stage of protein catabolism and extracellular matrix remodeling. Its metal active site composition corresponding to the maximal catalytic activity is still unknown, although prolidase function is of increasing interest due to the link with carcinogenesis and mutations in prolidase gene cause a severe connective tissue disorder. Here, using EPR and ICP-MS on human recombinant prolidase produced in Escherichia coli (hRecProl), the Mn(II) ion organized in a dinuclear Mn(II)-Mn(II) center was identified as the protein cofactor. Furthermore, thermal denaturation, CD/fluorescence spectroscopy and limited proteolysis revealed that the Mn(II) is required for the proper protein folding and that a protein conformational modification is needed in the transition from apo- to Mn(II)loaded-enzyme. The collected data provided a better knowledge of the human holo-prolidase and, although limited to the recombinant enzyme, the exact identity and organization of the metal cofactor as well as the conformational change required for activity were proven.
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PMID:A Mn(II)-Mn(II) center in human prolidase. 2299 80