• Korean Journal of Animal Reproduction
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• v.17 no.2
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• pp.165-171
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• 1993

While ornithine decarboxylase (ODC) is considered a key enzyme in the biosynthesis of polyamines, difluoromethylornithine(DFMO) acts as an inhibitor of polyamine synthesis. Cycling crossbred gilts were randomly assigned to one of two (treatment and control) groups (6/group). An indwelling silicone catheter was surgically implanted in the jugular vein of each animal. DFMO was dissolved in saline(200 mg/ml) and adminstered by i. m. injection at a dose of 80 mg/kg/day. The control group received an equivalent volume saline injection. DFMO was injected 3 times daily(08:00. 16:00. 24:00h) from day 16 of estrous cycle to 21 or until estrus. Once daily blood samples (10ml) were taken from day 14 until two days after the last DFMO treatment. Window blood samples were collected every 15 min for 8 h (from 08:00 to 16:00h) starting on day 16 and continuing until day 21 from one gilt per day. Serum progesterone (P$_4$), estradiol (E$_2$), LH and FSH were measured. Typical concentration profiles for P$_4$ and E$_2$ were seen during the follicular phase regardless of DFMO treatment. Injection of DFMO suppressed the preovulatory LH concentration in the serum(p<0.01) while having no effect on FSH profile. The present results indicate that DFMO had an inhibitory effect on LH secretion in the pig, but did not affect PI, E2 or FSH release.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.3
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• pp.440-447
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• 2009

Domestic ruminant animals are reared in diverse production systems, ranging from extensive systems under semi-arid and tropical conditions with poor feed resources to intensive systems in temperate and cold areas with high quality feed. Nitrogen (N) recycling between the body and gut of ruminants plays a key role in the adaptation to such diverse nutritional conditions. Ammonia and microbial protein produced in the gut and urea synthesized in the liver are major players in N-recycling transactions. In this review, we focus on the physiological factors affecting urea production and recycling. Sheep and buffalo probably have higher abilities to reabsorb urea from the kidney compared with cattle. This affects the degree of urea-N recycling between the body and gut at both low and high N intakes. The synthesis and gut entry of urea also differs between cattle bred for either dairy or beef production. Lactating dairy cows show a higher gut entry of urea compared with growing cattle. The synthesis and recycling of urea dramatically increases after weaning, so that the functional development of the rumen exerts an essential role in N transactions. Furthermore, high ambient temperature increases urea production but reduces urea gut entry. An increase in total urea flux, caused by the return to the ornithine cycle from the gut entry, is considered to serve as a labile N pool in the whole body to permit metabolic plasticity under a variety of physiological, environmental and nutritional conditions.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.220-226
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• 2005

Temperature and medium composition were changed with the aim of increasing growth and erythropoietin (EPO) production in EPO-producing Chinese hamster ovary (CHO) cells. We used the CHO cell line, IBE, and its derivative, CO5, which over-expresses the first two enzymes of the urea cycle, carbamoyl phosphate synthetase I (CPS I) and ornithine transcar-bamoylase (OTC). When supplements were added to the medium at $33\;^{\circ}C$, the growth of IBE and CO5 cells increased by $27\%\;and;26\%$, respectively and the maximum yield of EPO was increased by $40\%$ in both cell lines. The absolute EPO concentration in the CO5 cells was always $55{\sim}60\%$ higher than in the IBE cells. In addition, when the two cell lines were continuously cultured with supplements at $33\;^{\circ}C$ until their growth rates approached those at $37\;^{\circ}C$, the growth rates of both IBE and CO5 cells increased by $54\%$ and their maximum EPO levels increased by up to $73\%\;and\;56\%$, respectively. Therefore, the growth and EPO expression levels of CO5 cells increased 2.2-fold and 2.6-fold, respectively, compared to those of the IBE cells. These results indicate that adaptation to lower temperature as well as medium supplementation could be important for improving cell growth and EPO production.

• Journal of the Korean Child Neurology Society
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• v.25 no.3
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• pp.204-207
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• 2017

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH syndrome) is a neurometabolic disorder with highly variable clinical severity ranging from mild learning disability to severe encephalopathy. Diagnosis of HHH syndrome can easily be delayed or misdiagnosed due to insidious symptoms and incomplete biochemical findings, in that case, genetic testing should be considered to confirm the diagnosis. HHH syndrome is caused by biallelic mutations of SLC25A15, which is involved in the urea cycle and the ornithine transport into mitochondria. Here we report a boy with spastic paraplegia and asymptomatic younger sister who have compound heterozygous mutations of c.535C>T (p.R179^*) and c.116C>A (p.T39K) in the SLC25A15 gene. We identified that p.T39K mutation is a novel pathogenic mutation causing HHH syndrome and that p.R179^*, which is prevalent in Japanese and Middle Eastern heritage, is also found in the Korean population.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.77-79
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• 2002

The urea cycle, consisting of a series of six enzymatic reactions, plays key roles to prevent the accumulation of toxic nitrogenous compound and synthesize arginine de novo. Five well characterized diseases have been described, resulting from an enzymatic defect in the biosynthesis of one of the normally expressed enzyme. This presentation will focus on two representative diseases; ornithine transcarbamylase(OTC) deficiency and citrullinemia(argininosuccinate synthetase deficiency). OTC deficiency is one of the most common inborn error of urea cycle, which is inherited in X-linked manner. We identified 17 different mutations in 20 unrelated Korean patients with OTC deficiency; L9X, R26P, R26X, T44I, R92X, G100R, R141Q, G195R, M205T, H214Y, D249G, R277W, F281S, 853 del C, R320X, V323M and 10 bp del at nt. 796-805. These mutations occur at well conserved nucleotide sequences across species or CpG hot spot. The L9X and R26X lead to the disruption of leader sequences, required for directing mitochondrial localization of the OTC precursor. Their phenotypes are severe, and neonatal onset. The G100R, R277W and V323M mutations were uniquely identified in patients with late onset OTC deficiency. The other genotypes are associated with neonatal onset. Out of 20 patients with OTC deficiency, only 6 patients are alive; two were liver transplanted, and normal in growth and development at 2, 4 years after transplantation respectively. Citrullinemia is an autosomal recessive disease, caused by the mutations in the argininosuccinate synthetase(ASS) gene. We identified in 3 major mutations in 11 unrelated Korean patients with citrullinemia; G324S, $IVS6^{-2}$ A to G, and 67 bp ins at nt 1125-1126. Among these, the 67 base pair insertion mutation is novel. The allele frequency of each mutation is; G324S(45%), IVS6-2 A to G(32%), and 67 base pair insertion(14%). All patients are diagnosed at neonatal or infantile age. Interestingly, two patients presented with stroke like episode. Out of 11 patients, 5 patients died. Among 6 patients alive, one patient was successfully liver transplanted.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.15-21
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• 2021

Purpose: Urea cycle disorder (UCD) is an inherited inborn error of metabolism, acting on each step of urea cycle that cause various phenotypes. The purpose of the study was to investigate the long-term clinical consequences in different groups of UCD to characterize it. Methods: Twenty-two patients with UCD genetically confirmed were enrolled at Pusan National University Children's hospital and reviewed clinical features, biochemical and genetic features retrospectively. Results: UCD diagnosed in the present study included ornithine transcarbamylase deficiency (OTCD) (n=10, 45.5%), argininosuccinate synthase 1 deficiency (ASSD) (n=6, 27.3%), carbamoyl-phosphate synthetase 1 deficiency (CPS1D) (n=3, 13.6%), hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS) (n=2, 9.1%), and arginase-1 deficiency (ARG1D) (n=1, 4.5%). The age at the diagnosis was 32.7±66.2 months old (range 0.1 to 228.0 months). Eight (36.4%) patients with UCD displayed short stature. Neurologic sequelae were observed in eleven (50%) patients with UCD. Molecular analysis identified 37 different mutation types (14 missense, 6 nonsense, 6 deletion, 6 splicing, 3 delins, 1 insertion, and 1 duplication) including 14 novel variants. Progressive growth impairment and poor neurological outcomes were associated with plasma isoleucine and leucine concentrations, respectively. Conclusion: Although combinations of treatments such as nutritional restriction of proteins and use of alternative pathways for discarding excessive nitrogen are extensively employed, the prognosis of UCD remains unsatisfactory. Prospective clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth or neurological outcomes and decrease metabolic crisis episodes in patients with UCD.