Urinary levels of neopterin and biopterin in Autism

Messahel, Souad; Pheasant, Anne E.; Pall, Hardev; Ahmed-Choudhury, Jalal; Sungum-Paliwal, R.S; Vostanis, Panos

doi:10.1016/s0304-3940(97)00976-2

Cited by 45 publications

(24 citation statements)

References 21 publications

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“…However, mammals synthesize the pteridine tetrahydrobiopterin, and also catabolize pteridines (39). Engineered fruit accumulated free pteridines in the order of 0.36 mg per portion, which would represent Ͻ10% of the pteridines that humans excrete in the urine per day (40,41). In addition, it is reported that the medicinal legume, velvet bean, contains Ϸ470 nmol/g fresh weight of total pteridines in the pericarp (42), 25-fold more than our engineered fruit.…”

Section: Discussionmentioning

confidence: 82%

Folate biofortification of tomato fruit

Garza

Gregory²,

Hanson³

2007

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

215

142

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Folate deficiency leads to neural tube defects and other human diseases, and is a global health problem. Because plants are major folate sources for humans, we have sought to enhance plant folate levels (biofortification). Folates are synthesized from pteridine, p-aminobenzoate (PABA), and glutamate precursors. Previously, we increased pteridine production in tomato fruit up to 140-fold by overexpressing GTP cyclohydrolase I, the first enzyme of pteridine synthesis. This strategy increased folate levels 2-fold, but engineered fruit were PABA-depleted. We report here the engineering of fruit-specific overexpression of aminodeoxychorismate synthase, which catalyzes the first step of PABA synthesis. The resulting fruit contained an average of 19-fold more PABA than controls. When transgenic PABA-and pteridine-overproduction traits were combined by crossing, vine-ripened fruit accumulated up to 25-fold more folate than controls. Folate accumulation was almost as high (up to 15-fold) in fruit harvested green and ripened by ethylenegassing, as occurs in commerce. The accumulated folates showed normal proportions of one-carbon forms, with 5-methyltetrahydrofolate the most abundant, but were less extensively polyglutamylated than controls. Folate concentrations in developing fruit did not change in controls, but increased continuously throughout ripening in transgenic fruit. Pteridine and PABA levels in transgenic fruit were >20-fold higher than in controls, but the pathway intermediates dihydropteroate and dihydrofolate did not accumulate, pointing to a flux constraint at the dihydropteroate synthesis step. The folate levels we achieved provide the complete adult daily requirement in less than one standard serving. metabolic engineering ͉ vitamin

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Section: Discussionmentioning

confidence: 82%

Folate biofortification of tomato fruit

Garza

Gregory²,

Hanson³

2007

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

215

142

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“…Biopterin and neopterin were increased in the urine of 3-5-year-old autistic children (Messahel et al, 1998). Similarly, neopterin was increased in the plasma of autistic children (Sweeten et al, 2003).…”

Section: Neurologicmentioning

confidence: 90%

“…Neopterin levels are raised significantly during exacerbation of autoimmune diseases, and are lower during remission, thus acting as a marker of disease activity (Fuchs et al, 1993). Due to an increase in BH4 biosynthesis, levels of biopterin were also found to be increased in autistic patients (Messahel et al, 1998). IFNγ causes many types of cells to make BH4; any one of these cells could be the source of biopterin (Werner et al, 1989).…”

Section: Neurologicmentioning

confidence: 99%

Theoretical aspects of autism: biomarkers—a review

Ratajczak¹

2011

Journal of Immunotoxicology

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“…The same research group observed that the macrophage product neopterin, was higher in serum samples from individuals with ASD compared with controls, which may reflect increased cell-mediated immune activation and IFN-production (Sweeten et al, 2003). Higher IFN-and neopterin levels correlated significantly with elevated, circulating numbers of monocytes observed in autistic children (Sweeten et al, 2003) with elevated urine levels of neopterin and biopterin (Messahel et al, 1998).…”

Section: Maternal Immune System Status Findingsmentioning

confidence: 92%

Autoimmunity in Autism Spectrum Disorders

Al-Ayadhi¹

2011

Autism - A Neurodevelopmental Journey From Genes to Behaviour

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Urinary levels of neopterin and biopterin in Autism

Cited by 45 publications

References 21 publications

Folate biofortification of tomato fruit

Folate biofortification of tomato fruit

Theoretical aspects of autism: biomarkers—a review

Autoimmunity in Autism Spectrum Disorders

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