BH4-deficient hyperphenylalaninemia in Russia

Гундорова, П.; Kuznetcova, I.; Baydakova, Galina; Степанова, Анна; Itkis, Yulia S.; Какаулина, В. С.; Алферова, И. П.; Lyazina, Lidya V; Andreeva, Lilya P; Канивец, И. В.; Zakharova, Ekaterina; Kutsev, Sergey I.; Polyakov, A. V.

doi:10.1371/journal.pone.0249608

Cited by 13 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glycopeptide is a natural low-phenylalanine protein extracted from whey and is rich in valine, isoleucine, and threonine. After purification, glycopeptides mixed with other essential amino acids (tyrosine, tryptophan, arginine, cysteine, and histidine) can be used as a low-phenylalanine diet [6][7][8]. Dietary formulations containing glyco-macropeptides are better tasting and more acceptable than conventional lowphenylalanine diets.…”

Section: Discussionmentioning

confidence: 99%

“…In the event of a mutation in the gene encoding PAH, the activity of PAH synthesized by the liver is reduced or absent, or the deficiency of its coenzyme BH4 will lead to the blockage of the normal metabolic pathway of Phe in the body. As a result, substrates and secondary metabolites are accumulated in the body, and the reduction of normal metabolites and the accumulation of abnormal metabolites will trigger a series of PKU diseases characterized by intellectual impairment [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influencing Factors on the Use of Tetrahydrobiopterin in Patients with Phenylketonuria

Gao¹

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. To explore and analyze the influencing factors of tetrahydrobiopterin therapy in patients with phenylketonuria. Methods. 86 children with phenylketonuria (PKU) diagnosed and treated in our hospital from February 2019 to September 2021 were randomly enrolled. All the children underwent coenzyme hydroxybiopterin and urinary pterin spectrum analysis, and the children with deficiency received gene mutation testing. Results. The results of urine pterin analysis showed that 82 patients had higher urinary N and B contents than the normal reference values, with the N/B slightly higher than the normal B% within the normal range. 4 patients had extremely high urinary N/B and B% <5% and were diagnosed as BH4 deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, and a combined stress test was performed. The blood Phe level was (720–1200) μmol/L 3 h after Phe loading, and the blood Phe concentration decreased to (120–240) μmol/L 4–6 h after oral administration of 7.5 mg/kg BH4 tablet. After one week of treatment, the blood Phe concentration decreased significantly to 239 ± 173 μmol/L, with a decrease rate of 52.14 ± 25.28%. It shows that the application of tetrahydrobiopterin intervention therapy is effective in patients with PKU. The results of the full-length cDNA analysis of the PTPS gene showed that a total of 4 gene mutations were found. A C ⟶ T substitution occurred at the 259th base, and the 87th proline (Pro) in the coding region was converted to serine (Ser) (P87S). G ⟶ A substitution at base 286 converts aspartic acid (Asp) at position 96 of the coding region to asparagine (Asn) (D96N). A ⟶ G substitution occurs at the 155th base to convert asparagine (Asn) at position 52 of the coding region to serine (Ser) (N52S). G ⟶ C substitution occurs at the 430th base to convert glycine at position 144 (Gly) to arginine (Arg) (G144R). G144R is a new mutation type. The gene mutation types of the 4 patients were P87S/D96N, N52S/G144R, D96N/P87S, and P87S/P87S, all of which were from their parents, which conformed to the law of autosomal recessive inheritance. Conclusion. PKU is caused by the defect of phenylalanine hydroxylase activity in children, which causes phenylalanine metabolism disorder, and tetrahydrobiopterin intervention therapy can affect the activity of phenylalanine hydroxylase, increase the decline rate of blood Phe, significantly reduce the level of phenylalanine in children, and promote intellectual recovery. The dose of tetrahydrobiopterin should be tailored, with small doses for mild phenotypes and long-term treatment using even smaller doses.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influencing Factors on the Use of Tetrahydrobiopterin in Patients with Phenylketonuria

Gao¹

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…The QDPR gene encodes dihydropteridine reductase in the biopterin metabolism pathway, which catalyzes the quinone dihydrobiopterin reduction mediated by NADH (Chandrashekaran et al, 2018;Si et al, 2017). QDPR gene is involved in hyperphenylalaninemia and has no direct relationship with glucose metabolism (Gundorova et al, 2021). However, the QDPR gene can indirectly regulate glucose levels (Xu et al, 2014) through folic acid.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide selective detection of Mile red‐bone goat using next‐generation sequencing technology

Hong

Zhou

et al. 2021

Ecology and Evolution

View full text Add to dashboard Cite

show abstract

“…Hence, we speculated that PTS might be a novel potential target of LUAD, and we carried out experiments to study its effect and mechanism on LUAD. PTS has been extensively studied as an important cofactor for enzymes such as hepatic phenylalanine hydroxylase ( 23 , 24 ). Similarly, knockdown of PTS has been reported to suppress colorectal tumor cells growth ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

PTS is activated by ATF4 and promotes lung adenocarcinoma development via the Wnt pathway

Ma¹,

Wang²,

Li³

et al. 2022

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background: The effects and mechanism of 6-pyruvoyl-tetrahydropterin synthase (PTS) on lung adenocarcinoma (LUAD) were studied in LUAD cells and mice with subcutaneously transplanted tumors. Methods: PTS level in tissues and cells was tested by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). The impacts of PTS on cell viability, proliferation, apoptosis, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, transwell assay, and wound healing assay, respectively. The Cancer Genome Atlas (TCGA) analysis and dual luciferase assay were conducted to predict and verify the relationship between PTS and activating transcription factor 4 (ATF4). A mouse model was established by subcutaneous injection with cancer cells. Tumor volume was calculated as V = ab 2 /2. Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to measure cell proliferation and apoptosis in tumors.Results: PTS was highly expressed in LUAD. Higher PTS level was correlated with late clinical stages and poor survival of patients. Down-regulation of PTS inhibited the viability and proliferation and induced apoptosis of LUAD cells. PTS was activated by ATF4, and up-regulation of ATF4 reversed the inhibitory effect of PTS silencing on LUAD cells. Silencing of PTS inhibited the Wnt pathway. Down-regulation of PTS inhibited tumor growth in mice.Conclusions: PTS was highly expressed in LUAD. PTS was activated by ATF4 and promoted LUAD development via the Wnt pathway.

show abstract

BH4-deficient hyperphenylalaninemia in Russia

Cited by 13 publications

References 36 publications

Influencing Factors on the Use of Tetrahydrobiopterin in Patients with Phenylketonuria

Influencing Factors on the Use of Tetrahydrobiopterin in Patients with Phenylketonuria

Genome‐wide selective detection of Mile red‐bone goat using next‐generation sequencing technology

PTS is activated by ATF4 and promotes lung adenocarcinoma development via the Wnt pathway

Contact Info

Product

Resources

About