• 대한화장품학회:학술대회논문집
• /
• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book II
• /
• pp.12-25
• /
• 2003

L-camitine ($\beta$ -hydroxy-${\gamma}$ -trimethyl-ammoniumbutyric acid) is a small water-soluble molecule important in mammalian fat metabolism. It is essential for the normal oxidation of fatty acids by the mitochondria, and is involved in the trans-esterification and excretion of acyl-CoA esters. In this paper, to investigate the relationship between aging and L-camitine, we investigated the effects of in vitro MMP inhibition and activity and expression of UVA-induced MMP 1 in human skin fibroblasts. Fluorometric assays of the proteolytic activities of MMP-l were performed using fluorescent collagen substrates. ELISA (enzyme linked immuno sorbent assay), gelatin-substrate zymography, and RT-PCR ELISA techniques were used for the effects of L-camitine on MMP expression and activity, MMP mRNA expression in UVA irradiated fibroblast. L-camitine inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 2.45mM, and L-carnitine showed strong inhibition on MMP-2 (gelatinase) activity in UVA irradiated fibroblast by zymography. Also, UVA induced MMP expression was reduced 40% by treated with L-carnitine, and MMP-l mRNA expression was reduced dose-dependent manner. Therefore L-carnitine was able to significantly inhibition the MMP activity, regulation of MMP expression in protein and mRNA level. All these results suggest that L-carnitine may be useful as new anti-aging cofactor for protection against UVA induced MMP expression and activity.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제19권1호
• /
• pp.76-81
• /
• 2016

Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme functioning in mitochondrial fatty acid oxidation (FAO) of the liver. Patients with CPT1A deficiency have impaired mitochondrial FAO and display hypoketotic hypoglycemia and hepatic encephalopathy as typical manifestations. In this report, we present a case of CPT1A deficiency presenting jaundice as the first manifestation. A 1.9 years old boy showed jaundice and elevated levels of free and total carnitine were observed. From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified. At the age of 2.2 years, hypoglycemia, tachycardia, and altered mental status developed just after cranioplasty for craniosynostosis. High glucose infusion rate was required for recovery of his vital signs and mentality. Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date.

• 한국식품과학회지
• /
• 제47권1호
• /
• pp.95-102
• /
• 2015

본 연구는 분유모델시스템에 $\small{L}$-carnitine, pyridoxine hydrochloride, $\small{DL}$-${\alpha}$-tocopheryl acetate를 첨가하여 Maillard 반응에 의해 생성된 MRPs를 저감화 시키기 위한 최적조건을 찾기 위해 RSM의 CCD를 이용하였다. $\small{L}$-Carnitine ($X_1$), pyridoxine hydrochloride($X_2$), $\small{DL}$-${\alpha}$-tocopheryl acetate ($X_3$)의 농도를 독립변수로 하고 형광도와 HMF 함량을 종속변수로 각각 설정하였다. 종속변수 회귀식의 결정계수($R^2$)는 각각 0.942, 0.861로 반응표면분석 모델에 적합하였다. 형광도와 HMF 함량은 $\small{L}$-carnitine과 pyridoxine hydrochloride의 농도가 낮을 때 $\small{DL}$-${\alpha}$-tocopheryl acetate의 농도가 감소할수록 그 값이 급격히 감소하였다. $\small{L}$-Carnitine의 농도가 높을 때 pyridoxine hydrochloride의 농도가 $20{\mu}M$ 이하로 감소할수록 형광도가 감소하였고 HMF 함량은 $\small{L}$-carnitine의 농도에 관계없이 pyridoxine hydrochloride의 농도가 $20{\mu}M$ 이하로 감소할수록 감소하는 경향을 나타냈다. 본 실험에서 분유모델시스템에서 생성된 MRPs를 저감화 할 수 있는 최적조건으로 $\small{L}$-carnitine, pyridoxine hydrochloride, $\small{DL}$-${\alpha}$-tocopheryl acetate의 농도는 각각 2.26, 15.77, $20.63{\mu}M$이었다. 이때 형광도는 77.4%였고 HMF 함량은 248.7 ppb로 각각 유단백질-유당 마이얄 반응생성물(LC, lactose+sodium caseinate)대비 MRPs를 22.6, 23.1% 감소시킬 수 있다고 예측할 수 있었다. 또한, RSM을 통해 찾은 최적 조건의 실험값으로 형광도는 79.3%였고 HMF 함량은 247.6 ppb로 각각 LC대비 MRPs를 20.7, 17.8% 감소 시켰다. 따라서, $\small{L}$-carnitine, pyridoxine hydrochloride, $\small{DL}$-${\alpha}$-tocopheryl acetate의 최적화된 혼합을 통하여 분유 제조 시 MRPs 생성을 저감화 시킬 수 있을 것으로 생각된다.

• Preventive Nutrition and Food Science
• /
• 제4권1호
• /
• pp.75-78
• /
• 1999

Acetylcarnitine, a metabilite of carnitine, has been porven to be a potent inhibitor of ethanol oxidation in hepatocytes. It inhibits the activity of alcohol dehydrognase (ADH), but not the microsomal ethanol oxidizing system. which was significatly inhibited by acetylcarnitine at NAD ; acetylcarnitine $\leq$1. the main objectives of his study were to ascertain the interaction between acetylcarnitine and NAD on ADH activity and to elucidate whether different species have different effects. Tehpost-mocrosomal supernatant (PMS) was prepared from normal rat, guinea pig, mouse and broilers by differential centrifugation . Horse and yeast ADH were purchased from the Sigma Chemical Co. Prepared and purchased ADH are used for determination of ADH activity in the presence or absence of carnitine and acetylcar- nitine. Binding studies showed that acetylcarnitine did bind to ADH in a dose realted manner when low NAD ; acetylcar- nitine ratio was provided. It was found that the inhibitionof ADH activity occurred only when NAD concentration was less than the inhibitor concentration . Crystalline and crude ADH preparation from different vertebrate species wer inhibited by acetylcarnitine, whereas the yeast ADH was not affected by acetylcarnitine.

• Journal of Microbiology and Biotechnology
• /
• 제16권9호
• /
• pp.1468-1471
• /
• 2006

The last step in L-carnitine biosynthesis in eukaryotic organisms is mediated by ${\gamma}$-butyrobetaine hydroxylase (EC1.14.11.1), a dioxygenase that converts ${\gamma}$-butyrobetaine to L-carnitine. This enzyme was previously identified from rat liver and humans, and the peptide sequence of human ${\gamma}$-butyrobetaine hydroxylase was used to search the Neurospora crassa genome database, which led to an identification of an open reading frame (ORF) consisting of 1,407 bp encoding a polypeptide of 468 amino acids. When this protein was expressed in Saccharomyces cerevisiae, the crude cell-free extract exhibited ${\gamma}$-butyrobetaine hydroxylase activity.

• 운동영양학회지
• /
• 제16권1호
• /
• pp.1-9
• /
• 2012

Long chain fatty acids (LCFAs) are transported into cells via plasma transporters, are activated to fatty acyl-CoA by fatty acyl-CoA synthase (ACS), and enter mitochondria via the carnitine system (CPT1/CACT/CPT2). The mitochondrial carnitine system plays an obligatory role in β-oxidation of LCFAs by catalyzing their transport into the mitochondrial matrix. Fatty acyl-CoAs are oxidized via the β-oxidation pathway, which results in the production of acetyl-CoA. The acetyl-CoA can be imported into the tricarboxylic acid (TCA) cycle for oxidation in the mitochondrial matrix or can be used for malonyl-CoA synthesis by acetyl-CoA carboxylase 2 (ACC2) in the cytoplasm. In skeletal muscle, ACC2 catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, which is a potent endogenous inhibitor of carnitine palmitoyltransferase 1 (CPT1). Thus, ACC2 indirectly inhibits the influx of fatty acids into the mitochondria. Fatty acid metabolism can also be regulated by malonyl-CoA-mediated inhibition of CPT1.

• 한국임상약학회지
• /
• 제11권2호
• /
• pp.49-56
• /
• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is a naturally existing molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioefuivalence of two ALC tablets, $Nicetile^{TM} (Dong-A Pharmaceutical Co.) and $L-Cartin^{TM}$ (Kuhn Il Pharmaceutical Co.), according to the guidelines of Korea Food and Drug Administration (KFDA). The ALC release from the two ALC tablets in vitro was tested using KP VII Apparatus II method in various dissolution media (pH 1.2, 6.0 and 6.8). Twenty six normal male volunteers, $24.46\pm3.67$ years in age and $64.45\pm5.54$ kg in body weight, were divided into two groups and a randomized $2\times2$cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. The dissolution profiles of the two ALC tablets were similar in all the dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were $0.35\%,\;0.93\%\;and\;2.34\%$ respectively, when calculated against the $Nicetile^{TM} tablet. The powers $(1-\beta)\;for\;AUC_t$ , and Cmax were $98.72\%\;and\;85.48\%$, respectively. Minimum detectable differences $(\Delta)\;at\;\alpha=0.05\;and\;1-\beta=0.8$ were less than $20\%,\;(e.g.,\;13.21\%\;and\;18.42\%\;for\;AUC_t,\;and\;C_{max}$ respectively). The $90\%$ confidence intervals were within $\pm20\%\;(e.g.,\;-7.38\sim8.09\;and\;-9.86\sim11.72\;for\;AUC_t,\;and\;C_{max}$, respectively). These two parameters met the criteria of KFDA for bioequivalence, indicating that $L-Cartin^{TM}$ tablet is bioequivalent to $Nicetile^{TM} tablet.

• Journal of Pharmaceutical Investigation
• /
• 제31권1호
• /
• pp.49-55
• /
• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, $Nicetile^{TM}$ (Dong-A pharmaceutical Co., Ltd.) and $Neurocetil^{TM}$ (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, $22.80{\pm}2.76$ year in age and $63.07{\pm}7.98\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the $Nicetile^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 94.87% and 87.17%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 15.58% and 19.16% $AUC_t\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-11.84{\sim}6.41$ and $-10.57{\sim}11.88$for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Neurocetil^{TM}$ tablet is bioequivalent to $Nicetile^{TM}$ tablet.

• 생명과학회지
• /
• 제20권1호
• /
• pp.33-39
• /
• 2010

본 연구는 10주간 주 3회, 1회 운동시간 50분을 한 결과, 비만여고생을 대상으로 L-카르니틴 섭취와 복합운동이 신체조성, 혈중지질 및 아디포넥틴에 미치는 영향을 구명하기 위하여 체지방률 35% 이상 비만여고생을 대상으로 실험하였다. 신체조성에서는 운동과 카르니틴 섭취를 병행한 군에서 체중, 체지방량 및 체지방률이 유의하게 감소하였고, 제지방량이 유의하게 증가하였다. 혈중지질변화에서는 T-C는 대조군에서 집단 내 변화를 보였으며, TG는 복합운동과 카르니틴섭취를 병행한 군에서 유의하게 감소하였다. 아디포넥틴의 변화에서는 복합운동과 카르니틴섭취를 병행한 군이 유의하게 증가하였다. 이러한 연구결과를 토대로 보다 효과적인 운동프로그램과 적절한 식이요법으로 비만을 개선하는데 효과가 있을 것으로 사료된다.

• Applied Biological Chemistry
• /
• 제38권3호
• /
• pp.218-223
• /
• 1995

고염분으로 삼투압 스트레스를 받은 Yersinia enterocolitica ATCC 9610 세포내에 축적되는 osmolyte를 $^{13}C$ NMR을 통해 조사하였다. 자연계에 흔히 존재하는 가장 강력한 osmolyte로 알려진 glycine betaine의 삼투압 스트레스를 받은 Y. enterocolitica ATCC 9610 세포내 농도 (801.9 nmol/mg protein)는 삼투압 스트레스를 받지 않은 세포 (19.2 nmol/mg protein) 보다 41.8배 많이 검출되어 Y. enterocolitica ATCC 9610의 가장 주요한 osmolyte로 작용하였다. Proline도 284.8 nmol/mg protein의 농도로 검출되어 Y. enterocolitica ATCC 9610의 osmolyte로 작용하였다. Glycine betaine을 비롯한 각종 osmolyte가 삼투압 스트레스를 받은 Y. enterocolitica 세포성장에 미치는 역할을 검증하기 위해 Y. enterocolitica의 성장속도에 미치는 이들의 영향을 조사하였다. 2.5%의 NaCl이 첨가된 MMA 배지에 glycine betaine과 proline을 각각 첨가했을때, 1mM glycine betaine의 경우 osmolyte를 첨가하지 않은 대조구에 비해 성장속도가 3.6배 증가하였으며 5mM proline의 경우는 1.3배 증가하였다. Dimethylglycine도 2.5%의 NaCl을 첨가한 MMA 배지에 5mM의 농도로 첨가하였을때 대조구에 비해 성장속도가 3.1배 증가하였는데, monomethylglycine은 삼투압 스트레스를 받은 Y. enterocolitica의 성장에 어떤 영향도 미치지 못하였다. Carnitine은 2.5%의 NaCl이 첨가된 MMA 배지에 5mM의 농도로 첨가되었을때 대조구에 비해 2.4배 성장속도가 증가하였으며 choline은 성장에 어떤 영향도 미치지 못하였다. 이상의 결과로 glycine betaine은 Y. enterocolitica ATCC 9610의 가장 주요한 osmolyte로 작용하며, proline, dimethyglyine 그리고 carnitine도 Y. enterocolitica ATCC 9610의 osmolyte로 작용하여 삼투압 스트레스를 받은 Y. enterocolitica ATCC 9610의 성장속도를 증가시켰다.