• BMB Reports
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• v.43 no.9
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• pp.584-592
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• 2010

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.

• Proceedings of the Korean Society of Propulsion Engineers Conference
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• 2017.05a
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• pp.128-130
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• 2017

$NaBH_4$ was added to improve the water reactivity of aluminum powder as a solid propellant for underwater propulsion. Aluminum powders showed different combustion characteristics depending on the amount of $NaBH_4$ added. When $NaBH_4$ was added, it was burned by reaction with water even at a temperature much lower than the boiling point. In this study, it was confirmed that $NaBH_4$ is an effective additive to accelerate the vapor reaction with Al powder.

• Korean Chemical Engineering Research
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• v.53 no.1
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• pp.11-15
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• 2015

Sodium borohydride, $NaBH_4$, shows a number of advantages as hydrogen source for portable proton exchange membrane fuel cells(PEMFCs). Properties of $NaBH_4$ hydrolysis reaction using unsupported Co-B, Co-P-B catalyst were studied. BET surface area of catalyst, yield of hydrogen, effect of $NaBH_4$ concentration and durability of catalyst were measured. The BET surface area of unsupported Co-B catalyst was $75.7m^2/g$ and this value was 18 times higher than that of FeCrAlloy supported Co-B catalyst. The hydrogen yield of $NaBH_4$ hydrolysis reaction by unsupported catalysts using 20~25 wt% $NaBH_4$ solution was 97.6~98.5% in batch reactor. The hydrogen yield decrease to 95.3~97.0% as the concentration of $NaBH_4$ solution increase to 30 wt%. The loss of unsupported catalyst was less than that of FeCrAlloy supported catalyst during $NaBH_4$ hydrolysis reaction and the loss increased with increasing of $NaBH_4$ concentration. In continuous reactor, hydrogen yield of $NaBH_4$ hydrolysis was 90% using 1.2 g of unsupported Co-P-B catalyst with $3{\ell}/min$ hydrogen generation rate.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.110-117
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• 2015

All infants should be screened for phenylketonuria (PKU) within the three days of life, in order to allow timely dietary intervention to protect children with PKU from neurologic damage in Korea. A commonly used cut-off level for diagnosis of PKU is $240{\mu}mol/L$ (4 mg/dL). Up to 2% of cases of hyperphenylalaninemias (HPA) detected by the screening test will account for a disorder of $BH_4$ metabolism. Therefore, analysis of blood or urinary pterins is essential, backed up with measurement of DHPR activity, as this allows differentiation of $BH_4$ disorders. A $BH_4$ loading test and measurement of neurotransmitters in CSF provide further important information to the severity of $BH_4$ deficiency and $BH_4$ loading test can detect patients with $BH_4$ deficiency and $BH_4$ responsive PKU. Several protocols for $BH_4$ loading test have been described, involving treatment with $BH_4$ for periods ranging from 1 day to 1 month, and using doses of $BH_4$ of 10-20 mg/kg. There is general agreement that a reduction on blood phenylalanine of at least 30% in response to $BH_4$ loading indicates a clinically significant effect, although in some tests a lower cut-off value may be defined for individual patients, or no specific cut-off value is proposed. The frequency of $BH_4$ responsiveness is highest in patients with mild HPA and mild to moderate PKU resulting from PAH mutations with residual activity.

• Journal of the Korean Society of Propulsion Engineers
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• v.23 no.3
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• pp.88-95
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• 2019

The hydrogen torch ignition system has been widely used to ignite a pure aluminum for aluminum powder combustion system because of its simple ignition method. However, the conventional hydrogen torch ignition system has a disadvantage that requires a high-pressure tank to supply hydrogen, which leads to the increase of the weight. In order to solve this problem, a hydrogen ignition system using $NaBH_4$, a solid chemical hydride, was designed in this study. The thermal decomposition of $NaBH_4$ was initiated approximately at $500^{\circ}C$ and hydrogen was generated. The parameters affecting the thermal decomposition characteristics of $NaBH_4$ were analyzed and the aluminum combustion test was carried out using $NaBH_4$-based hydrogen ignition system to study the applicability to a practical aluminum-combustion propulsion system.

• Korean Chemical Engineering Research
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• v.49 no.5
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• pp.516-520
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• 2011

Sodium borohydride, $NaBH_4$, shows a number of advantages as hydrogen source for portable proton exchange membrane fuel cells (PEMFCs). The hydrogen yield of sodium borohydride hydrolysis reaction was studied. The effect of temperature, $NaBH_4$ concentration, NaOH concentration and catalyst type on the hydrogen yield from $NaBH_4$ hydrolysis reaction were measured. The catalysts of Co-P/Cu, Co-B/Cu and Co-P-B/Cu were used in this study and there was no different effect of these catalysts on the hydrogen yield from $NaBH_4$. Under the temperature of $60^{\circ}C$, the hydrogen yield decreased as $NaBH_4$ concentration increased due to formation of gel with by-products and reactants. The gel formed during $NaBH_4$ hydrolysis reaction diminished the hydrogen evolution rate and total volume of hydrogen. Addition of NaOH stabilizer enhanced the formation of gel and then decreased the hydrogen yield.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.86-92
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• 2016

Purpose: The $BH_4$ loading test is an important test that distinguishes PKU from $BH_4$ deficiency and identifies the $BH_4$ reactivity of PKU patients. Phenylalanine and $BH_4$ loading tests are useful methods that can shorten the length of hospital stay while improving patients' convenience. However, sufficient research on the dose of phenylalanine loading and $BH_4$ administration time after the loading has not been carried out. The present study investigates the effectiveness of the existing phenylalanine loading method by analyzing the medical records of six patients who underwent the $BH_4$ loading test after taking 100 mg/kg of phenylalanine patients. Methods: The medical records of six patients who underwent the $BH_4$ load test after taking 100 mg/kg of phenylalanine were examined out of 207 patients who were followed up in the Genetic Metabolic Clinic in Soonchunhyang University Hospital. All of the six patients had a low phenylalanine diet. First, they were taking 100 mg/kg of phenylalanine. 3 hours later, 20 mg/kg of $BH_4$ were loaded. The phenylalanine levels in the blood were continuously measured at 1, 2, 4, 6, 8, 12, and 24 hours by setting the time the $BH_4$ was loaded as the basal. Results: The average of the highest phenylalanine concentrations of six patients was $20.0{\pm}11.70mg/dL$. One reached the highest concentration seven hours after taking phenylalanine; another reached it five hours after that, and the remaining three reached it four hours after that. Only one patient reached the highest concentration within three hours. The phenylalanine levels of four out of six patients (66%) rose above $400{\mu}mol/L$ after being loaded with phenylalanine. The phenylalanine levels of the remaining two were 6.1 mg/dL ($366{\mu}mol/L$) and 5 mg/dL ($300{\mu}mol/L$), respectively. Conclusion: One of six patients (16%) reached the highest concentration three hours after taking 100 mg/kg of phenylalanine and four patients (66%) reached $400{\mu}mol/L$ or higher phenylalanine levels. There were patients whose phenylalanine levels did not rise above $400{\mu}mol/L$ using a commonly known test method; moreover, this method had the disadvantage of reaching the highest concentration after more than three hours. Therefore, it is considered that taking 200 mg/kg or more of phenylalanine and performing $BH_4$ loading four to six hours after taking phenylalanine are helpful in proper diagnosis.

• Transactions of the Korean hydrogen and new energy society
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• v.20 no.4
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• pp.300-308
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• 2009

In a pursuit of the development of alternative mobile power sources with a high energy density, a planar and air-breathing PEMFCs with a new type of hydrogen cartridge which uses onsite $H_2$ generated from sodium borohydride ($NaBH_4$) hydrolysis have been investigated for use in advanced power systems. Two types of $H_2$ generation through $NaBH_4$ hydrolysis are available: (1) using organic acids such as sulphuric acid, malic acid, and sodium hydrogen carbonate in aqueous solution with solid $NaBH_4$ and (2) using solid selected catalysts such as Pt, Ru, CoB into the stabilized alkaline $NaBH_4$ solution. It might therefore be relevant at this stage to evaluate the relative competitiveness of the two methods mentioned above. The effects of flow rate of stabilized $NaBH_4$ solution, MEA (Membrane Electrode Assembly) improvement, and type and flow control of the catalytic acidic solution have been studied and the cell performances of the planar, air-breathing PEMFCs using $NaBH_4$ has been measured from aspects of power density, fuel efficiency, energy density, and fast response of cell. In our experiments, planar, air-breathing PEMFCs using $NaBH_4$ achieved to maximum power density of 128mW/$cm^2$ at 0.7V and energy efficiency of 46% and has many advantages such as low operating temperature, sustained operation at a high power density, compactness, the potential for low cost and volume, long stack life, fast star-up and suitability for discontinuous operation.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.177-183
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• 2010

Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BBinduced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with $N^G$-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2005.04a
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• pp.53-60
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• 2005

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting $1\%$ of the population above the age of 65 and is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although the underlying cause of dopaminergic cell death or the mechanism by which these cells degenerate is still not clearly understood, oxidative stress, mitochondrial dysfunction, and protein misfolding are thought to play important roles in the dopaminergic degeneration in PD. Tetrahydrobiopterin (BH4) is synthesized exclusively in the monoaminergic, including dopaminergic, cells and serves as an endogenous and obligatory cofactor for syntheses of the potential oxidative stressors dopamine and nitric oxide. In addition to its contribution toward the syntheses of these two potentially toxic molecules, BH4 itself can directly generate oxidative stress. BH4 undergoes oxidation during the hydroxylation reaction as well as nonenzymatic autooxidation to produce hydrogen peroxide and superoxide radical. We have previously suggested BH4 as an endogenous molecule responsible for the dopaminergic neurodegeneration. BH4 exerts selective toxicity to dopamine-producing cells via generation of oxidative stress, mitochondrial dysfunction, and apoptosis. BH4 also induces morphological, biochemical, and behavioral characteristics associated with PD in vivo. BH4 as well as enzyme activity and gene expression of GTP cyclohydrolase I, the rate-limiting enzyme in BH4 synthesis pathway, are readily upregulated by cellular changes such as calcium influx and by various stimuli including stress situations. This points to the possibility that cellular availability of BH4 might be increased in aberrant conditions, leading to increased extracellular BH4 subsequent degeneration. The fact that BH4 is specifically and endogenously synthesized in dopaminergic cells, Is readily upregulated, and generates oxidative stress-related cell death provides physical relevance of this molecule as an attractive candidate with which to explain the mechanism of pathogenesis of PD.