Cellular transport of l-histidine in Hartnup disease

Halvorsen, S; Hygstedt, Olof; Jagenburg, Rudolf; Sjaastad, Ottar

doi:10.1172/jci106121

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…The association of urine histidine levels with rare variants in SLC6A19 in our study highlights the encoded amino acid transporter as the relevant transport protein. This is in agreement with findings from patients with Hartnup disease, where bi-allelic loss-of-function mutations in SLC6A19 lead to a reabsorption defect of histidine in renal tubular cells 45 . Associations between rare variants and lipid metabolites on the other hand may be better detected in blood, such as for APOA5 and diacylglycerol 18 , consistent with extra-renal handling and/or excretion.…”

Section: Discussionsupporting

confidence: 92%

Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism

et al. 2021

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Metabolite levels in urine may provide insights into genetic mechanisms shaping their related pathways. We therefore investigate the cumulative contribution of rare, exonic genetic variants on urine levels of 1487 metabolites and 53,714 metabolite ratios among 4864 GCKD study participants. Here we report the detection of 128 significant associations involving 30 unique genes, 16 of which are known to underlie inborn errors of metabolism. The 30 genes are strongly enriched for shared expression in liver and kidney (odds ratio = 65, p-FDR = 3e−7), with hepatocytes and proximal tubule cells as driving cell types. Use of UK Biobank whole-exome sequencing data links genes to diseases connected to the identified metabolites. In silico constraint-based modeling of gene knockouts in a virtual whole-body, organ-resolved metabolic human correctly predicts the observed direction of metabolite changes, highlighting the potential of linking population genetics to modeling. Our study implicates candidate variants and genes for inborn errors of metabolism.

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Section: Discussionsupporting

confidence: 92%

Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism

et al. 2021

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“…After ingestion of carnosine, serum concentrations of 3-alanine and of histidine were within normal limits, whereas after ingestion of an equimolar mixture of the two constituent amino acids, absorption of histidine was grossly reduced but f-alanine absorption was normal. Halvorsen, Hygstedt, Jagenburg, and Sjaastad (1969) have recently published a study of L-histidine absorption in two cases of Hartnup disease. They found extremely flat tolerance curves for serum histidine comparable to the results of Navab and Asatoor (1970).…”

Section: Discussionmentioning

confidence: 99%

Intestinal absorption of two dipeptides in Hartnup disease

Asatoor¹,

Cheng²,

Edwards³

et al. 1970

Gut

125

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SUMMARY The results of oral tolerance tests of two dipeptides and of their constituent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide.

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“…This simplifies interpretation of the results. T o take a specific example, the failure of the plasma concentration of His to rise after free His in our patients might be contributed to by increased renal and tissue clearance (12), but the large rise in the concentration of this amino acid after the peptide-containing preparation indicates that these factors are unlikely to be entirely responsible, and suggests that malabsorption of the free amino acid plays an important part.…”

Section: Discussionmentioning

confidence: 73%

Intestinal Absorption of Amino Acids and Peptides in Hartnup Disorder

et al. 1976

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Absorption of free and peptide-bound amino acids was investigated in a girl with Hartnup disorder aged 26 months. Plasma levels of amino acids were followed after oral administration of (1) an amino acid mixture simulating casein and (2) an equivalent dose of a partial enzymic hydrolysate of casein containing oligopeptides in addition to free amino acids. The results suggested that many neutral amino acids were poorly absorbed when given in the free form, but much more readily absorbed when given as peptides. Unexpectedly, the results also suggested that glutamic acid was poorly absorbed when given in the free form. The results obtained with threonine could not be interpreted. There was an increased renal clearance of many neutral amino acids, including glycine, but clearance of proline was not increased. Most amino acids with an increased renal clearance also appeared to be poorly absorbed when given by mouth in the free form.

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Cellular transport of l-histidine in Hartnup disease

Cited by 8 publications

References 12 publications

Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism

Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism

Intestinal absorption of two dipeptides in Hartnup disease

Intestinal Absorption of Amino Acids and Peptides in Hartnup Disorder

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