RESUMO
This paper presents a preliminary result carried out in the Besut River basin, Terengganu, Malaysia to determine the selected trace metal concentrations. Concentrations of dissolved Pb, Cu, and Fe during the present study were in the range of 3.3-8.3 microg/L Pb, 0.1-0.3 microg/L Cu, and 1.1-12.3 microg/L Fe. For the particulate fraction concentrations of Pb, Cu, and Fe ranged from 1.0 to 3.6 microg/L, 0.3 to 2.8 microg/L, and 114 to 1,537 microg/L, respectively. The concentrations of metals in this study area, in general, were lower than those reported for other study areas. Higher metal concentrations measured in the wet monsoon season suggest that the input was mainly due to terrestrial runoff.
Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Rios , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Malásia , Rios/química , Estações do Ano , Poluentes do Solo/químicaRESUMO
Unnatural analogues of sialic acid can be delivered to mammalian cell surfaces through the metabolic transformation of unnatural N-acetylmannosamine (ManNAc) derivatives. In previous studies, mannosamine analogues bearing simple N-acyl groups up to five carbon atoms in length were recognized as substrates by the biosynthetic machinery and transformed into cell surface sialoglycoconjugates [Keppler, O. T., et al. (2001) Glycobiology 11, 11R-18R]. Such structural alterations to cell surface glycans can be used to probe carbohydrate-dependent phenomena. This report describes our investigation into the extent of tolerance of the pathway toward additional structural alterations of the N-acyl substituent of ManNAc. A panel of analogues with ketone-containing N-acyl groups that varied in the length or steric bulk was chemically synthesized and tested for metabolic conversion to cell surface glycans. We found that extension of the N-acyl chain to six, seven, or eight carbon atoms dramatically reduced utilization by the biosynthetic machinery. Likewise, branching from the linear chain reduced metabolic conversion. Quantitation of metabolic intermediates suggested that cellular metabolism is limited by the phosphorylation of the N-acylmannosamines by ManNAc 6-kinase in the first step of the pathway. This was confirmed by enzymatic assay of the partially purified enzyme with unnatural substrates. Identification of ManNAc 6-kinase as a bottleneck for unnatural sialic acid biosynthesis provides a target for expanding the metabolic promiscuity of mammalian cells.
Assuntos
Ácido N-Acetilneuramínico/biossíntese , Ácido N-Acetilneuramínico/química , Carbono/química , Núcleo Celular/metabolismo , Citosol/metabolismo , Relação Dose-Resposta a Droga , Células HL-60 , Células HeLa , Hexosaminas/química , Humanos , Células Jurkat , Cetonas/química , Espectrometria de Massas , Modelos Biológicos , Modelos Químicos , Ácido N-Acetilneuramínico/metabolismo , Fosforilação , Ligação Proteica , Espectrometria de Massas por Ionização por Electrospray , Especificidade por Substrato , Fatores de TempoRESUMO
Oligosaccharides on proteins and lipids play central roles in human health and disease. The molecular analysis of glycoconjugate function has benefited tremendously from new methods for their chemical synthesis, which provides homogeneous material not attainable from biosynthetic systems. Still, glycoconjugate synthesis requires the manipulation of multiple stereocenters and protecting groups and remains the domain of a few expert laboratories around the world. This Account summarizes chemoselective approaches for assembling homogeneous glycoconjugates that attempt to reduce the barriers to their synthesis. The objective of these methods is to make glycoconjugate synthesis accessible to a broader community, thereby accelerating progress in glycobiology.