Chronic liver diseases are a serious health problem worldwide. One of the frequently reported glycan alterations in liver disease is aberrant fucosylation, which was suggested as a marker for noninvasive serologic monitoring. We present a case study that compares site specific glycoforms of four proteins including haptoglobin, complement factor H, kininogen-1, and hemopexin isolated from the same patient. Our exoglycosidase-assisted LC-MS/MS analysis confirms the high degree of fucosylation of some of the proteins but shows that microheterogeneity is protein- and site-specific. MSn analysis of permethylated detached glycans confirms the presence of LeY glycoforms on haptoglobin, which cannot be detected in hemopexin or complement factor H; all three proteins carry Lewis and H epitopes. Core fucosylation is detectable in only trace amounts in haptoglobin but with confidence on hemopexin and complement factor H, where core fucosylation of the bi-antennary glycans on select glycopeptides reaches 15-20% intensity. These protein-specific differences in fucosylation, observed in proteins isolated from the same patient source, suggest that factors other than up-regulation of enzymatic activity regulate the microheterogeneity of glycoforms. This has implications for selection of candidate proteins for disease monitoring and suggests that site-specific glycoforms have structural determinants, which could lead to functional consequences for specific subsets of proteins or their domains.
- MeSH
- glykoproteiny krev sekrece MeSH
- glykosylace MeSH
- hepatitida C krev MeSH
- jaterní cirhóza krev virologie MeSH
- játra sekrece MeSH
- konformace sacharidů MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- posttranslační úpravy proteinů * MeSH
- sacharidové sekvence MeSH
- sekvence aminokyselin MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- biotransformace MeSH
- extracelulární matrix MeSH
- imunologické faktory farmakologie terapeutické užití MeSH
- játra sekrece MeSH
- komplementární terapie metody MeSH
- léčivé přípravky MeSH
- ledviny sekrece MeSH
- lidé MeSH
- lymfatický systém sekrece MeSH
- systém (enzymů) cytochromů P-450 MeSH
- xenobiotika imunologie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- MeSH
- ABC transportéry farmakokinetika MeSH
- finanční podpora výzkumu jako téma MeSH
- játra enzymologie fyziologie sekrece MeSH
- lidé MeSH
- mnohočetná léková rezistence fyziologie genetika imunologie MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům farmakokinetika fyziologie genetika MeSH
- transportní proteiny farmakokinetika MeSH
- xenobiotika farmakokinetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
