The Effect of a Low-Protein Diet and Dietary Supplementation of Threonine on Tyrosine and 2-(2-Nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-Induced Corneal Lesions, the Extent of Tyrosinemia, and the Activity of Enzymes Involved in Tyrosine Catabolism in the Rat

Lock, EA; Gaskin, P; Ellis, MK; Robinson, Mervyn; Wm, Provan; Ll, Smith

doi:10.1006/taap.1998.8404

Cited by 19 publications

(7 citation statements)

References 18 publications

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“…Secondly, in rats, threonine supplementation has been shown to partly prevent the ocular lesions caused by tyrosine toxicity [72-75]. Although the underlying mechanism is still unknown, it has been suggested that blood tyrosine concentrations decrease if tyrosine administration is combined with threonine [73,74].…”

Section: Resultsmentioning

confidence: 99%

“…Although the underlying mechanism is still unknown, it has been suggested that blood tyrosine concentrations decrease if tyrosine administration is combined with threonine [73,74]. Therefore, it can be hypothesized that threonine could protect against ocular lesions by lowering blood tyrosine concentrations either by competition with tyrosine and/or phenylalanine for uptake at the gut-blood barrier or in the renal tubules, or by promoting tyrosine oxidation in the liver [75]. However, as threonine supplementation has also been shown to partly prevent ocular lesions with NTBC administration without reducing blood tyrosine concentrations, the positive effects of threonine do not seem to be solely due to a reduction of hypertyrosinemia [75].…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, it can be hypothesized that threonine could protect against ocular lesions by lowering blood tyrosine concentrations either by competition with tyrosine and/or phenylalanine for uptake at the gut-blood barrier or in the renal tubules, or by promoting tyrosine oxidation in the liver [75]. However, as threonine supplementation has also been shown to partly prevent ocular lesions with NTBC administration without reducing blood tyrosine concentrations, the positive effects of threonine do not seem to be solely due to a reduction of hypertyrosinemia [75]. To conclude, additional phenylalanine supplementation in HT1 patients clearly increased the otherwise very low blood phenylalanine concentrations (level 4), but the possible clinical effects remain to be investigated.…”

Section: Resultsmentioning

confidence: 99%

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Single amino acid supplementation in aminoacidopathies: a systematic review

Vliet

Derks

Rijn

et al. 2014

Orphanet J Rare Dis

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Aminoacidopathies are a group of rare and diverse disorders, caused by the deficiency of an enzyme or transporter involved in amino acid metabolism. For most aminoacidopathies, dietary management is the mainstay of treatment. Such treatment includes severe natural protein restriction, combined with protein substitution with all amino acids except the amino acids prior to the metabolic block and enriched with the amino acid that has become essential by the enzymatic defect. For some aminoacidopathies, supplementation of one or two amino acids, that have not become essential by the enzymatic defect, has been suggested. This so-called single amino acid supplementation can serve different treatment objectives, but evidence is limited. The aim of the present article is to provide a systematic review on the reasons for applications of single amino acid supplementation in aminoacidopathies treated with natural protein restriction and synthetic amino acid mixtures.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Single amino acid supplementation in aminoacidopathies: a systematic review

Vliet

Derks

Rijn

et al. 2014

Orphanet J Rare Dis

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show abstract

“…Early investigations into the administration of nitisinone demonstrated that corneal injury can first be detected as soon as 1 week after dosing, but usually takes longer to reach its peak at around 4 weeks [15]. More recent studies show that in some investigations, no patients demonstrated any corneal symptoms whilst being on nitisinone for a number of years [16].…”

Section: Discussionmentioning

confidence: 99%

Osteoarticular cells tolerate short-term exposure to nitisinone—implications in alkaptonuria

et al. 2015

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“…As a side effect of nitisinone treatment, plasma tyrosine levels are elevated in treated HT-1 patients, but the magnitude of elevation is reduced by coinstitution of a low-protein diet. The pharmacokinetics, pharmacodynamics, and toxicology of nitisinone have been well studied in mice and humans (28)(29)(30)(31)(32). Standard doses of 1-2 mg/kg/d in humans and up to 160 mg/kg/d in mice have been well tolerated (33,34).…”

Section: Introductionmentioning

confidence: 99%

Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism

Onojafe¹,

Adams²,

Simeonov³

et al. 2011

J. Clin. Invest.

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Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin. We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice homozygous for either the Tyr c-2J null allele or the Tyr c-h allele, which model OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyr c-h/c-h mice manifested increased pigmentation in their fur and irides and had more pigmented melanosomes. High levels of tyrosine improved the stability and enzymatic function of the Tyr c-h protein and also increased overall melanin levels in melanocytes from a human with OCA-1B. These results suggest that the use of nitisinone in OCA-1B patients could improve their pigmentation and potentially ameliorate vision loss.

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The Effect of a Low-Protein Diet and Dietary Supplementation of Threonine on Tyrosine and 2-(2-Nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-Induced Corneal Lesions, the Extent of Tyrosinemia, and the Activity of Enzymes Involved in Tyrosine Catabolism in the Rat

Cited by 19 publications

References 18 publications

Single amino acid supplementation in aminoacidopathies: a systematic review

Single amino acid supplementation in aminoacidopathies: a systematic review

Osteoarticular cells tolerate short-term exposure to nitisinone—implications in alkaptonuria

Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism

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