<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kawanishi, Kunio</style></author><author><style face="normal" font="default" size="100%">Saha, Sudeshna</style></author><author><style face="normal" font="default" size="100%">Diaz, Sandra</style></author><author><style face="normal" font="default" size="100%">Vaill, Michael</style></author><author><style face="normal" font="default" size="100%">Sasmal, Aniruddha</style></author><author><style face="normal" font="default" size="100%">Siddiqui, Shoib S</style></author><author><style face="normal" font="default" size="100%">Choudhury, Biswa</style></author><author><style face="normal" font="default" size="100%">Sharma, Kumar</style></author><author><style face="normal" font="default" size="100%">Chen, Xi</style></author><author><style face="normal" font="default" size="100%">Schoenhofen, Ian C</style></author><author><style face="normal" font="default" size="100%">Sato, Chihiro</style></author><author><style face="normal" font="default" size="100%">Kitajima, Ken</style></author><author><style face="normal" font="default" size="100%">Freeze, Hudson H</style></author><author><style face="normal" font="default" size="100%">Münster-Kühnel, Anja</style></author><author><style face="normal" font="default" size="100%">Ajit Varki</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Evolutionary conservation of human ketodeoxynonulosonic acid production is independent of sialoglycan biosynthesis.</style></title><secondary-title><style face="normal" font="default" size="100%">J Clin Invest</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Clin Invest</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021 Mar 01</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">131</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Human metabolic incorporation of nonhuman sialic acid (Sia) N-glycolylneuraminic acid into endogenous glycans generates inflammation via preexisting antibodies, which likely contributes to red meat-induced atherosclerosis acceleration. Exploring whether this mechanism affects atherosclerosis in end-stage renal disease (ESRD), we instead found serum accumulation of 2-keto-3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (Kdn), a Sia prominently expressed in cold-blooded vertebrates. In patients with ESRD, levels of the Kdn precursor mannose also increased, but within a normal range. Mannose ingestion by healthy volunteers raised the levels of urinary mannose and Kdn. Kdn production pathways remained conserved in mammals but were diminished by an M42T substitution in a key biosynthetic enzyme, N-acetylneuraminate synthase. Remarkably, reversion to the ancestral methionine then occurred independently in 2 lineages, including humans. However, mammalian glycan databases contain no Kdn-glycans. We hypothesize that the potential toxicity of excess mannose in mammals is partly buffered by conversion to free Kdn. Thus, mammals probably conserve Kdn biosynthesis and modulate it in a lineage-specific manner, not for glycosylation, but to control physiological mannose intermediates and metabolites. However, human cells can be forced to express Kdn-glycans via genetic mutations enhancing Kdn utilization, or by transfection with fish enzymes producing cytidine monophosphate-Kdn (CMP-Kdn). Antibodies against Kdn-glycans occur in pooled human immunoglobulins. Pathological conditions that elevate Kdn levels could therefore result in antibody-mediated inflammatory pathologies.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">&lt;p&gt;https://www.ncbi.nlm.nih.gov/pubmed/33373330?dopt=Abstract&lt;/p&gt;
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