Uptake, Metabolism and Excretion of Orally and Intravenously Administered,14C- and3H-LabeledN-Acetylneuraminic Acid Mixture in the Mouse and Rat

Nöhle, Ulrich; Schauer, Roland

doi:10.1515/bchm2.1981.362.2.1495

Cited by 52 publications

(44 citation statements)

References 13 publications

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“…Taken together, these data indicate that the capacity to synthesize Neu5Gc may not be lost completely in humans. Further studies will be needed to ascertain whether this represents the up-regulation of another minor pathway for the synthesis of Neu5Gc, such as the suggested use of the donor glycolyl-CoA (69,70), or the incorporation of Neu5Gc from dietary sources (71).…”

Section: Discussionmentioning

confidence: 99%

A mutation in human CMP-sialic acid hydroxylase occurred after theHomo-Pandivergence

Chou

Takematsu

Díaz

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

527

432

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Sialic acids are important cell-surface molecules of animals in the deuterostome lineage. Although humans do not express easily detectable amounts of N-glycolylneuraminic acid (Neu5Gc, a hydroxylated form of the common sialic acid N-acetylneuraminic acid, Neu5Ac), it is a major component in great ape tissues, except in the brain. This difference correlates with lack of the hydroxylase activity that converts CMP-Neu5Ac to CMP-Neu5Gc. Here we report cloning of human and chimpanzee hydroxylase cDNAs. Although this chimpanzee cDNA is similar to the murine homologue, the human cDNA contains a 92-bp deletion resulting in a frameshift mutation. The isolated human gene also shows evidence for this deletion. Genomic PCR analysis indicates that this deletion does not occur in any of the African great apes. The gene is localized to 6p22-p23 in both humans and great apes, which does not correspond to known chromosomal rearrangements that occurred during hominoid evolution. Thus, the lineage leading to modern humans suffered a mutation sometime after the common ancestor with the chimpanzee and bonobo, potentially affecting recognition by a variety of endogenous and exogenous sialic acid-binding lectins. Also, the expression of Neu5Gc previously reported in human fetuses and tumors as well as the traces detected in some normal adult humans must be mediated by an alternate pathway.

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Section: Discussionmentioning

confidence: 99%

A mutation in human CMP-sialic acid hydroxylase occurred after theHomo-Pandivergence

Chou

Takematsu

Díaz

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

527

432

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“…Our group demonstrated that 0.23% of a labelled dose of sialic acid was taken up into the brain of 3-day-old piglets by 2 h after intravenous administration (Downing et al, 2001). However, older animals did not show significant incorporation of labelled sialic acid after acute dosing (Nöhle & Schauer, 1981). Morgon and Winick (unpublished results) also found that when sialic acid was injected after 30 days of age (by which time the rat brain had completed its growth), neither behaviour nor brain biochemistry was affected.…”

Section: Exogenous Administration Of Sialic Acidmentioning

confidence: 94%

“…Rat intestinal cell walls are highly permeable to free sialic acid. Radioactively labelled forms of sialic acid and sialyl lactose were found to be well absorbed (B90%) by rat pups, 30% being retained in the body, and 3-4% in the brain after 6 h (Nöhle & Schauer, 1981). However, Brand-Miller et al (1998) demonstrated with breath hydrogen methodology that most HMOs resist digestion in the small intestine of breast-fed infants and undergo fermentation in the colon.…”

Section: Digestion and Absorption Of Sialic Acidmentioning

confidence: 99%

“…Oral and intravenous administration of radioactively labelled forms of both sialic acid and sialyl-lactose (a trisaccharide) were found to be well absorbed (B90%) by 20-day-old rat pups, 30% being retained in the body, and 3-4% in the brain after 6 h (Nöhle & Schauer, 1981). Our group demonstrated that 0.23% of a labelled dose of sialic acid was taken up into the brain of 3-day-old piglets by 2 h after intravenous administration (Downing et al, 2001).…”

Section: Exogenous Administration Of Sialic Acidmentioning

confidence: 99%

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The role and potential of sialic acid in human nutrition

2003

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Sialic acids are a family of nine-carbon acidic monosaccharides that occur naturally at the end of sugar chains attached to the surfaces of cells and soluble proteins. In the human body, the highest concentration of sialic acid (as N-acetylneuraminic acid) occurs in the brain where it participates as an integral part of ganglioside structure in synaptogenesis and neural transmission. Human milk also contains a high concentration of sialic acid attached to the terminal end of free oligosaccharides, but its metabolic fate and biological role are currently unknown. An important question is whether the sialic acid in human milk is a conditional nutrient and confers developmental advantages on breast-fed infants compared to those fed infant formula. In this review, we critically discuss the current state of knowledge of the biology and role of sialic acid in human milk and nervous tissue, and the link between sialic acid, breastfeeding and learning behaviour.

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“…In our previous preclinical studies, even with one-third of sialic acid amounts in 6'-sialyllactose in molar ratio, it provided a similar prophylactic effect as free NeuAc and ManNAc in preventing the development of myopathic phenotype in the GNE myopathy mice (Malicdan et al, 2009). When given orally, 6'-sialyllactose has been reported to have a longer retention in blood than NeuAc (Nö ule and Schauer, 1981). In this study, we evaluated the effects of a sustained compound, 6'-sialyllactose, in the recovery of cellular sialylation and myopathic phenotype in symptomatic old GNE myopathy mice.…”

mentioning

confidence: 92%

Sialyllactose ameliorates myopathic phenotypes in symptomatic GNE myopathy model mice

Yonekawa

Malicdan

Cho

et al. 2014

Brain

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Patients with GNE myopathy, a progressive and debilitating disease caused by a genetic defect in sialic acid biosynthesis, rely on supportive care and eventually become wheelchair-bound. To elucidate whether GNE myopathy is treatable at a progressive stage of the disease, we examined the efficacy of sialic acid supplementation on symptomatic old GNE myopathy mice that have ongoing, active muscle degeneration. We examined the therapeutic effect of a less metabolized sialic acid compound (6'-sialyllactose) or free sialic acid (N-acetylneuraminic acid) by oral, continuous administration to 50-week-old GNE myopathy mice for 30 weeks. To evaluate effects on their motor performance in living mice, spontaneous locomotion activity on a running wheel was measured chronologically at 50, 65, 72 and 80 weeks of age. The size, force production, and pathology of isolated gastrocnemius muscle were analysed at the end point. Sialic acid level in skeletal muscle was also measured. Spontaneous locomotion activity was recovered in 6'-sialyllactose-treated mice, while NeuAc-treated mice slowed the disease progression. Treatment with 6'-sialyllactose led to marked restoration of hyposialylation in muscle and consequently to robust improvement in the muscle size, contractile parameters, and pathology as compared to NeuAc. This is due to the fact that 6'-sialyllactose is longer working as it is further metabolized to free sialic acid after initial absorption. 6'-sialyllactose ameliorated muscle atrophy and degeneration in symptomatic GNE myopathy mice. Our results provide evidence that GNE myopathy can be treated even at a progressive stage and 6'-sialyllactose has more remarkable advantage than free sialic acid, providing a conceptual proof for clinical use in patients.

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Uptake, Metabolism and Excretion of Orally and Intravenously Administered,¹⁴C- and³H-LabeledN-Acetylneuraminic Acid Mixture in the Mouse and Rat

Cited by 52 publications

References 13 publications

A mutation in human CMP-sialic acid hydroxylase occurred after theHomo-Pandivergence

A mutation in human CMP-sialic acid hydroxylase occurred after theHomo-Pandivergence

The role and potential of sialic acid in human nutrition

Sialyllactose ameliorates myopathic phenotypes in symptomatic GNE myopathy model mice

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