• Title/Summary/Keyword: Ornithine cycle

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A Case of Molecular Diagnosis of Ornithine Transcarbamylase Deficiency (분자 유전학적 검사로 진단된 Ornithine Transcarbamylase Deficiency 1 예)

  • Lee, Eun-Sil
    • Journal of Yeungnam Medical Science
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    • v.24 no.2
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    • pp.322-328
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    • 2007
  • Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea cycle metabolism; it is inherited in an X-linked manner. The OTC catalyzes the third step of the urea cycle, the conversion of ornithine and carbamyl phosphate to citrulline. Deficiency of OTC leads to the accumulation of ammonia, causing neurological deficits. In most affected hemizygote males, OTC deficiency manifests as hyperammonemic coma that often leads to death in the newborn period, and those who recover from the coma may be neurologically impaired due to the sequelae of the hyperammonemic encephalopathy. In some, late-onset manifestations develop. We report a male neonate with early onset OT deficiency that had apnea and was comatous. On mutation analysis using DNA sequencing after polymerase chain reaction (PCR) amplification of the 10 exons, deletions of 10 bases in codon 285, causing a frame shift was detected in exon 8. The mother and a sister were diagnosed as female carriers. Therefore, genetic counseling and the risk assessment could be provided to the family.

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Ornithine Decarboxylase Activity in Porcine Reproductive Tissues (Gilt에 있어서 Tissue내에 함유되어 있는 Ornithine Decarboxylase의 활성)

  • ;J.R. Diehl
    • Korean Journal of Animal Reproduction
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    • v.17 no.2
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    • pp.159-164
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    • 1993
  • The tissue levels of ornithine decarboxylase (ODC) during the estrous cycle and pregnancy were investigated in the pig. Sexually mature female cycling pigs were used. One animal was sacrificed on estrous cycle days 3, 10, 17, 18, 19, 20 and during pregnancy on day 11. 12, B. 14, 18, 19, 20, 48, 50 and 52. Tissues from the hypothalamus, pituitary, uterus, ovary and skeletal muscle were removed. They were homogenized in buffer, and supernatants were used for measurement of protein concentration and ODC activity. The release of $^14$CO$_2$ from radiolabeled ornithine was proportional to the amout of protein added over the range of 0.125~4mg and to the incubation time. ODC appered to have some relationship with the biological functions of the pituitary, ovary and uterus during the reproductive period, especially on day 19 of the estrous cycle, while it showed no such activities in hypothalamus and skeletal muscle of mature pigs. Uterine tissues had significantly more ODC activity than other tissues tested(p < 0.05).

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Neurological Outcome of Patients with Late-onset Ornithine Transcarbamylase Deficiency (지발형 오르니틴 트랜스카바미라제 결핍증 환자들의 신경학적 예후)

  • Jang, Kyung Mi;Hwang, Su-Kyeong
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.22 no.1
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    • pp.15-20
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    • 2022
  • The most common urea cycle disorder is ornithine transcarbamylase deficiency. More than 80 percent of patients with symptomatic ornithine transcarbamylase deficiency are late-onset, which can present various phenotypes from infancy to adulthood. With no regards to the severity of the disease, characteristic fluctuating courses due to hyperammonemia may develop unexpectedly, and can be precipitated by various metabolic stressors. Late-onset ornithine transcarbamylase deficiency is not merely related to a type of genetic variation, but also to the complex relationship between genetic and environmental factors that result in hyperammonemia; therefore, it is difficult to predict the prevalence of neurological symptoms in late-onset ornithine transcarbamylase deficiency. Most common acute neurological manifestations include psychological changes, seizures, cerebral edema, and death; subacute neurological manifestations include developmental delays, learning disabilities, intellectual disabilities, attention-deficit/hyperactivity disorder, executive function deficits, and emotional and behavioral problems. This review aims to increase awareness of late-onset ornithine transcarbamylase deficiency, allowing for an efficient use of biochemical and genetic tests available for diagnosis, ultimately leading to earlier treatment of patients.

Content Analyses of Fiber, Protein and Amino Acids of Fully Ripe Fruits of Korea Native Squash, Cucurbita moschata Poir (한국재래종 호박 완숙과의 섬유질, 단백질 및 아미노산 함량 비교분석)

  • Youn, Sun-Joo;Jun, Ha-Joon;Kang, Sun-Chul
    • Applied Biological Chemistry
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    • v.47 no.4
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    • pp.403-408
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    • 2004
  • We studied active substances like crude cell wall components, crude protein, composing amino acids and free amino acids including orinithine cycle-related amino acids such as asparagine, ornithine and citrullin in fully ripe fruits of Korean native squash, Cucurbita moschata Poir. Crude protein content of 'Jeju 2' was the highest with $2,830\;{\mu}g/g$, while 'Sangju' was the lowest with $1,319\;{\mu}g/g$. Regarding the contents of crude cell wall components, fruit 'Kanghaw' was the highest with 2,961 mg% while 'Namhea' was the lowest with 1,582 mg%. Pectin contents of crude cell wall components were the highest in 'Kanghaw' (2,198 mg%) followed by 'Jeju 2' (2,178 mg%) and 'Jeju l' (1,461 mg%). The main contents of amino acids in squash were glutamic acid, aspartic acid, lysine, leucine and valine, which comprised to be more than 50% of total amino acid contents. Especially, in 'Jeju 2' aspartic acid and threonine were not detected. In fully ripe fruits, a total of 34 kinds of free amino acids were detected including 8 kinds of essential amino acids (histidine, isoleucine, leucine, lysine, phenylalanine, methionine, threonine and valine). More than 50% of the total free amino acids were aspartic acid and asparagine, and also all varieties were detected in ornithine, citrullin, and arginine, which are related to Ornithine cycle. There was a big difference in the contents of arginine in all varieties whereas the contents of ornithine and citrullin were very similar. 'Teaan' 29.34% was 7 times higher than 'Namhea' 4.30% in regards to arginine contents.

A neonate with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome from a consanguineous Pakistani family

  • Kim, Yoo-Mi;Lim, Han Hyuk;Gang, Mi Hyeon;Lee, Yong Wook;Kim, Sook Za;Kim, Gu-Hwan;Yoo, Han-Wook;Ko, Jung-Min;Chang, Meayoung
    • Journal of Genetic Medicine
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    • v.16 no.2
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    • pp.85-89
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    • 2019
  • Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.

Characterization of a gene encoding ornithine carbamoyltransferase from rice

  • Islam Sikdar, Shafiqul;Kim, Jung-Sup
    • Journal of Plant Biotechnology
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    • v.36 no.4
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    • pp.397-402
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    • 2009
  • Ornithinine carbamoyltransferase (OTC) is an enzyme that catalyzes the key step in arginine biosynthesis in bacteria and plants. OTC is also involved in the urea cycle and deficiency of the enzyme in human leads to disease. The argF gene encoding OTC has been reported in many bacteria and few plants. Here we report the characterization of a gene encoding OTC from rice (OsOTC). Analysis of a cDNA sequence from rice revealed that the full-length open reading frame of OsOTC consisted of 367 amino acids, corresponding to a protein of approximately 39.7 kDa. The predicted amino acid sequence of OsOTC harbor distinct five OTC signature sites and is highly homologous to that of enzymes of plants, animals and many bacterial OTCs. Expression of OsOTC in argF mutants of Escherichia coli showed that the gene was able to functionally complement to the mutant. These results suggest that the OsOTC encode a protein for ornithine carbamoyltransferase in rice.

Adenovirus-mediated Expression of Both Antisense Ornithine Decarboxylase and S-adenosylmethionine Decarboxylase Induces G1 Arrest in HT-29 Cells

  • Gong, Lei;Jiang, Chunying;Zhang, Bing;Hu, Haiyan;Wang, Wei;Liu, Xianxi
    • BMB Reports
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    • v.39 no.6
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    • pp.730-736
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    • 2006
  • To evaluated the effect of recombinant adenovirus Ad-ODC-AdoMetDCas which can simultaneously express both antisense ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) on cell cycle distribution in colorectal cancer cell and investigated underlying regulatory responses, human colorectal cancer cells HT-29 were cultured in RPMI 1640 medium and infected with Ad-ODC-AdoMetDCas. Cell cycle progression was detected by flow cytometry analysis. The expression levels of cell cycle regulated proteins were measured by Western blot analysis. The mRNA level of cyclin D1 was measured by RT-PCR. And a luciferase reporter plasmid of cyclin D1 promoter was constructed to observe the effect of Ad-ODC-AdoMetDCas on cyclin D1 promoter activity. The results showed that recombinant adenovirus Ad-ODC-AdoMetDCas significantly induced $G_1$ arrest, decreased levels of cyclin D1 protein and mRNA and suppressed the promoter activity. Ad-ODC-AdoMetDCas also inhibited nuclear translocation of $\beta$-catenin. In conclusion, downregulation of ODC and AdoMetDC mediated by Ad-ODC-AdoMetDCas transfection induces $G_1$ arrest in HT-29 cells and the arrest was associated with suppression of cyclin D1 expression and inhibition of $\beta$-catenin nuclear translocation. As a new anticancer reagent, the recombinant adenovirus Ad-ODC-AdoMetDCas holds promising hope for the therapy of colorectal cancers.

The Ornithine Transcarbamylase (OTC) Deficiency Identified by a Novel Mutation (새로운 유전자 돌연변이로 확진된 Ornithine Transcarbamylase (OTC) 결핍증 1례)

  • Song, Ari;Lee, Kiwuk;Yang, Aram;Kim, Jinsup;Park, Hyung-Doo;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.16 no.3
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    • pp.148-154
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    • 2016
  • A urea cycle disorder is a condition caused by a defect of the enzymes in the urea cycle, and deficiency of ornithine transcarbamylase (OTC), which converts carbamoyl phosphate and ornithine into citrulline, is the most common type of the disorder. OTC deficiency induces the accumulation of precursors of urea, ammonia, and glutamine, leading to neurological symptoms including hypotonia, respiratory failure, seizure, lethargy, and coma and sometimes to death. Because OTC deficiency is inherited in an X-linked manner, typical symptoms such as vomiting, poor feeding, and lethargy appear mainly in male neonates. We recently had a case that presented with neonatal onset lethargy, vomiting, and apnea in a 4-day-old boy. He was diagnosed with OTC deficiency by biochemical phenotype, including hyperammonemia and an increased orotic acid level in the urine. Genetic analysis of the OTC gene showed a novel mutation c.780_781insCAGGCAGTGT (p.Ile261Glnfs*35). He was treated for hyperammonemia using continuous venovenous hemofiltration (CVVH) at 118 hours after birth. After 4 days of CVVH, his consciousness and blood ammonia concentration were normalized, and he was discharged at the age of 53 days. At around 12 months of age, bilateral femur fractures and osteomyelitis occurred in this patient. Two months after the fracture, he died of septic shock, insulin-resistant hyperglycemia, and multi-organ failure.

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Enhancement of Erythropoietin Production from Chinese Hamster Ovary(CHO) Cells by Introduction of the Urea Cycle Enzymes, Carbamoyl Phosphate Synthetase I and Ornithine Transcarbamylase

  • Kim, Na-Young;Lee, Yun-Jeong;Kim, Hyung-Jin;Choi, Jung-Ho;Kim, Jung-Kwon;Chang, Kern-Hee;Kim, Jung-Hoe;Kim, Hong-Jin
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.844-851
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    • 2004
  • Efficient mammalian erythropoietin (EPO)-expression systems are required for therapeutic applications. The accumulation of ammonia is a major problem in the production of recombinant proteins in cultured animal cells. To counter this problem we introduced the first two genes of the urea cycle, carbamoyl phosphate synthetase (CPSI) and ornithine transcarbamylase (OTC), into IBE Chinese Hamster Ovary (CHO) cells by stable transfection. The resulting cell line, CO5, had a higher growth rate and accumulated less ammonia per cell than the parental cell line, IBE. In addition, it produced 2 times more EPO than the parent, and the purified EPO contained a higher proportion of acidic isoforms with approximately 15% more sialic acid.

The efficient Erythropoietin expression system in Chinese Hamster Ovary cells by introduction of urea cycle enzymes

  • Lee, Yun-Jeong;Kim, Jung-Kwon;Kim, Hyung-Jin;Kim, Na-Young;Kim, Jung-Hoe;Kim, Hong-Jin
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.231.2-231.2
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    • 2003
  • The efficient EPO (Erythropoietin) expression system in Chinese Hamster Ovary (CHO) cells was devised through the removal of ammonium ion accumulated in the media by introducing urea cycle enzymes. Previously, we developed C05 cell by transfecting the carbamoly phosphate synthase (CPS) and ornithine transcarbamoylase (OTC) into the EPO expressing CHO cell, IBE. (omitted)

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