Document Detail


Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid.
MedLine Citation:
PMID:  22692204     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although N-acetyl groups are common in nature, N-glycolyl groups are rare. Mammals express two major sialic acids, N-acetylneuraminic acid and N-glycolylneuraminic acid (Neu5Gc). Although humans cannot produce Neu5Gc, it is detected in the epithelial lining of hollow organs, endothelial lining of the vasculature, fetal tissues, and carcinomas. This unexpected expression is hypothesized to result via metabolic incorporation of Neu5Gc from mammalian foods. This accumulation has relevance for diseases associated with such nutrients, via interaction with Neu5Gc-specific antibodies. Little is known about how ingested sialic acids in general and Neu5Gc in particular are metabolized in the gastrointestinal tract. We studied the gastrointestinal and systemic fate of Neu5Gc-containing glycoproteins (Neu5Gc-glycoproteins) or free Neu5Gc in the Neu5Gc-free Cmah(-/-) mouse model. Ingested free Neu5Gc showed rapid absorption into the circulation and urinary excretion. In contrast, ingestion of Neu5Gc-glycoproteins led to Neu5Gc incorporation into the small intestinal wall, appearance in circulation at a steady-state level for several hours, and metabolic incorporation into multiple peripheral tissue glycoproteins and glycolipids, thus conclusively proving that Neu5Gc can be metabolically incorporated from food. Feeding Neu5Gc-glycoproteins but not free Neu5Gc mimics the human condition, causing tissue incorporation into human-like sites in Cmah(-/-) fetal and adult tissues, as well as developing tumors. Thus, glycoproteins containing glycosidically linked Neu5Gc are the likely dietary source for human tissue accumulation, and not the free monosaccharide. This human-like model can be used to elucidate specific mechanisms of Neu5Gc delivery from the gut to tissues, as well as general mechanisms of metabolism of ingested sialic acids.
Authors:
Kalyan Banda; Christopher J Gregg; Renee Chow; Nissi M Varki; Ajit Varki
Related Documents :
398704 - Methylation patterns of trna at different concentrations of dimethylsulphate.
11284704 - Editing by a trna synthetase: dna aptamer-induced translocation and hydrolysis of a mis...
20925334 - Expanding the genetic code of yeast for incorporation of diverse unnatural amino acids ...
6290814 - Synthesis and biological properties of ovine corticotropin-releasing factor (crf).
644654 - Mechanisms of the anemia in trypanosomiasis: studies on the role of the hemolytic fatty...
2513324 - Phospholipid remodeling in human neutrophils. parallel activation of a deacylation/reac...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2012-10-31     Revised Date:  2013-08-20    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28852-64     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of California San Diego, La Jolla, California 92093-0687, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Heterophile / metabolism*
Autoantigens / metabolism*
Gastrointestinal Tract / metabolism*
Glycoproteins / genetics,  metabolism*
Humans
Meat Products*
Mice
Mice, Knockout
Neuraminic Acids / metabolism*
Species Specificity
Grant Support
ID/Acronym/Agency:
R01 GM032373/GM/NIGMS NIH HHS; R01GM32373/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Heterophile; 0/Autoantigens; 0/Glycoproteins; 0/Neuraminic Acids; 1113-83-3/N-glycolylneuraminic acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Metabolism of vertebrate amino sugars with N-glycolyl groups: incorporation of N-glycolylhexosamines...
Next Document:  Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating the intracellular fate of ...