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Delayed Motor Milestones Achievement in Infancy Associates with Perturbations of Amino Acids and Lipid Metabolic Pathways.

ABSTRACT: The relationship between developmental milestone achievement in infancy and later cognitive function and mental health is well established, but underlying biochemical mechanisms are poorly described. Our study aims to discover pathways connected to motor milestone achievement during infancy by using untargeted plasma metabolomic profiles from 571 six-month-old children in connection with age of motor milestones achievement (Denver Developmental Index) in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) mother-child cohort. We used univariate regression models and multivariate modelling (Partial Least Squares Discriminant Analysis: PLS-DA) to examine the associations and the VDAART (Vitamin D Antenatal Asthma Reduction Trial) cohort for validation. The univariate analyses showed 62 metabolites associated with gross-motor milestone achievement (p < 0.05) as well as the PLS-DA significantly differentiated between slow and fast milestone achievers (AUC = 0.87, p = 0.01). Higher levels of tyramine-O-sulfate in the tyrosine pathway were found in the late achievers in COPSAC (p = 0.0002) and in VDAART (p = 0.02). Furthermore, we observed that slow achievers were characterized by higher levels of fatty acids and products of fatty acids metabolism including acyl carnitines. Finally, we also observed changes in the lysine, histidine, glutamate, creatine and tryptophan pathways. Observing these metabolic changes in relation to gross-motor milestones in the first year of life, may be of importance for later cognitive function and mental health.

SUBMITTER: Vinding RK

PROVIDER: S-EPMC7570268 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Delayed Motor Milestones Achievement in Infancy Associates with Perturbations of Amino Acids and Lipid Metabolic Pathways.

Vinding Rebecca Kofod RK Rago Daniela D Kelly Rachel S RS Gürdeniz Gözde G Rasmussen Morten Arendt MA Stokholm Jakob J Bønnelykke Klaus K Litonjua Augusto A AA Weiss Scott T ST Lasky-Su Jessica J Bisgaard Hans H Chawes Bo Lund BL

Metabolites 20200819 9

The relationship between developmental milestone achievement in infancy and later cognitive function and mental health is well established, but underlying biochemical mechanisms are poorly described. Our study aims to discover pathways connected to motor milestone achievement during infancy by using untargeted plasma metabolomic profiles from 571 six-month-old children in connection with age of motor milestones achievement (Denver Developmental Index) in the Copenhagen Prospective Studies on Ast ...[more]

PMID: 32824932

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Project description:Time-resolved fluorescence and differential scanning calorimetry (DSC) were used to examine how two amino acids, L-phenylalanine (L-PA) and N-acetyl-DL-tryptophan (NAT), affect the temperature-dependent membrane affinity of two structurally similar coumarin solutes for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles. The 7-aminocoumarin solutes, coumarin 151 (C151) and coumarin 152 (C152), differ in their substitution at amine position-C151 is a primary amine, and C152 is a tertiary amine-and both solutes show different tendencies to associate with lipid bilayers consistent with differences in their respective log-P-values. Adding L-PA to the DPPC vesicle solution did not change C151's propensity to remain freely solvated in aqueous solution, but C152 showed a greater tendency to partition into the hydrophobic bilayer interior at temperatures below DPPC's gel-liquid crystalline transition temperature (Tgel-lc). This finding is consistent with L-PA's ability to enhance membrane permeability by disrupting chain-chain interactions. Adding NAT to DPPC-vesicle-containing solutions changed C151 and C152 affinity for the DPPC membranes in unexpected ways. DSC data show that NAT interacts strongly with the lipid bilayer, lowering Tgel-lc by up to 2°C at concentrations of 10 mM. These effects disappear when either C151 or C152 is added to solution at concentrations below 10 μM, and Tgel-lc returns to a value consistent with unperturbed DPPC bilayers. Together with DSC results, fluorescence data imply that NAT promotes coumarin adsorption to the vesicle bilayer surface. NAT's effects diminish above Tgel-lc and imply that unlike L-PA, NAT does not penetrate into the bilayer but instead remains adsorbed to the bilayer's exterior. Taken in their entirety, these discoveries suggest that amino acids-and by inference, polypeptides and proteins-change solute affinity for lipid bilayers with specific effects that depend on individualized amino-acid-lipid-bilayer interactions.

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Delayed Motor Milestones Achievement in Infancy Associates with Perturbations of Amino Acids and Lipid Metabolic Pathways.

Publications

Delayed Motor Milestones Achievement in Infancy Associates with Perturbations of Amino Acids and Lipid Metabolic Pathways.

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