• BMB Reports
• /
• 제33권1호
• /
• pp.54-58
• /
• 2000

Recent research results regarding the very long chain transmembrane ${\alpha},{\omega}-dicarboxylic$ components in the membrane of extremophilic eubacteria, such as Sarcina ventriculi, Thennotoga maritima, and Thermoanaerobacter ethanolicus have raised interesting questions concerning the physical and biochemical function on these components in the membrane. In order to understand the dynamic characteristics of these acids which reside in the bilayer membrane, 580 ps molecular dynamic simulations at 300 K were performed for two model systems. These systems were the bilayer with regular chain (C16:0 or C18:1) fatty acid methyl esters and the fatty acid bilayer containing very long chain transmembrane dicarboxylic acid methyl esters (${\alpha},{\omega}-15,16-dimethyltriacotane-dioate$ dimethyl ester; C32:0). Our analyses indicate that very long chain transmembrane dicarboxylic acids have a noticeable influence on the bilayer dynamics at a sub-nanosecond time scale. The center-ofmass mean-squared-displacement (MSD) of regular chain fatty acids adjacent to the very long chain transmembrane dicarboxylic acids decreased, the long-axis order parameter increased, and the reorientational motions of methylene groups were slowed along the hydrocarbon chains. These results indicate that the very long chain transmembrane dicarboxylic acids reduce the molecular order of the whole bilayer membrane.

• Asian-Australasian Journal of Animal Sciences
• /
• 제29권11호
• /
• pp.1646-1652
• /
• 2016

Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and metabolism and is sufficient to induce specific metabolic processes, including de novo lipid biosynthesis. Elongation of very-long-chain fatty acids 1 (ELOVL1) is a ubiquitously expressed gene and the product of which was thought to be associated with elongation of carbon (C) chain in fatty acids. In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on ELOVL1 expression and docosahexaenoic acid (DHA, C22:6 n-3) synthesis in bovine mammary epithelial cells (BMECs). We found that rapamycin decreased the relative abundance of ELOVL1 mRNA, ELOVL1 expression and the level of DHA in a time-dependent manner. These data indicate that ELOVL1 expression and DHA synthesis are regulated by mTORC1 in BMECs.

• Biomolecules & Therapeutics
• /
• 제22권2호
• /
• pp.83-92
• /
• 2014

Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology.

• Journal of Microbiology and Biotechnology
• /
• 제10권3호
• /
• pp.386-393
• /
• 2000

Recent research on the fatty acyl chains in the membrane lipids in Sarcina ventriculi has shown that unusually long chain bifunctional fatty acyl components are the major components of the total lipid. However, these studies did not yield any information on the complete structures of the lipid species containing these fatty acids. In this study, the structures of a new family of glucolipids containing bifunctional acyl chains are described. These structures were determined using NMR(Nuclear Magnetic Resonance) Spectroscopy, GC (Gas Chromatography)/MS (Mass Spectrometry), FTIR (Fourier Transform Infrared) spectroscopy, and FAB (Fast Atom Bombardment) mass spectrometric studies. One of the major bifunctional acyl components of the $\alpha$-glucolipids was an $\omega$-formylmethyl ester indicating the presence of plasmalogen. The general structure of the lipid components was one in which the two head groups were separated by a membrane-spanning acyl species. One head group component is a glycerol moiety of each head group, and the other is a glyceryl clucoside. Two regular chain fatty acids, one on the glycerol moiety of each head group, are also present and meet in the middle of the membrane, roughly equidistant from each head group.

• 대한유전성대사질환학회지
• /
• 제22권1호
• /
• pp.1-8
• /
• 2022

Long-chain fatty acid oxidation disorders (LC-FAOD) are an autosomal recessive inherited rare disease group that result in an acute metabolic crisis and chronic energy deficiency owing to the deficiency in an enzyme that converts long-chain fatty acids into energy. LC-FAOD includes carnitine palmitoyltransferase type 1 (CPT1), carnitine-acylcarnitine translocase (CACT), carnitine palmitoyltransferase type 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), and trifunctional protein (TFP) deficiencies. Common symptoms of LC-FAOD are hypoketotic hypoglycemia, cardiomyopathy, and myopathy. Depending on symptom onset, the disease can be divided as neonatal period, late infancy and early childhood, adolescence, or adult onset, but symptoms can appear at any time. The neonatal screening test (NBS) can be used to identify the characteristic plasma acylcarnitine profiles for each disease and confirmed by deficient enzyme analysis or molecular testing. Before introduction of NBS, the mortality rate of LC-FAOD was very high. With NBS implementation as routine neonatal care, the mortality rate was dramatically decreased, but severe symptoms such as rhabdomyolysis recur frequently and affect the quality of life. Triheptanoin (Dojolvi^®), the first drug for pediatric and adult patients with molecularly confirmed LC-FAOD, has recently been approved by the US Food and Drug Administration in 2020. In this review, the diagnosis of LC-FAOD and treatment including triheptanoin are summarized.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
• /
• pp.129.1-129.1
• /
• 2000

• Bulletin of the Korean Chemical Society
• /
• 제23권12호
• /
• pp.1778-1784
• /
• 2002

Novel membrane lipids containing the unusual very long chain fatty $acid{\alpha}{\omega}-1316-dimethyloctacosanedioate$, dimethyl. Ester (DME C30) was isolated and purified from thermophilic anaerobic eubacterium, Thermoanaerobacter ethanolicus. Structures of the lipids containing the bifunctional fatty acyl components were proposed by various analyses such as $^1H,\;^{13}C,\;^{31}P$ nuclear magnetic resonance (NMR), Fourier transform infrared(FTIR) spectroscopy, gas chromatography/mass spectrometry (GC/MS) and fast atom bombardment mass spectrometry (FAB/MS). Combined with the GC/MS, $^1H,\;and\;^{13}C$NMR data, we confirmed that the head groups of the lipids contained the glycerol and/or glucosamine molecules. $^{31}P$ NMR spectrum also showed that the lipids contained phosphate in a phosphodiester linkage. The proposed structures of these novel lipid components were the ones in which two head groups were linked by the membrane spanning fatty acyl component(DME C30)and regular chain fatty acids on glycerol moiety of each head group.

• 대한유전성대사질환학회지
• /
• 제12권1호
• /
• pp.49-53
• /
• 2012

X 연관 부신백질이영양증(adrenoleukodystrophy, ALD)은 과산화소체베타산화과정(peroxisomal ${\beta}$-oxidation)의 장애로 매우긴사슬지방산(very long chain fatty acids, VLCFA)이 신경계의 백질과 부신피질 및 고환에 축척된다. 이 질환은 과산화소체막단백질(peroxisomal membrane protein)을 형성하는 Xq28에 위치하는 ATP-binding cassette, subfamily D, member 1 (ABCD1) 유전자 돌연변이에 의해 주로 발생한다. X 연관 ALD는 다양한 임상양상을 보이는데 전형적인 소아대뇌형 부신백질이영양증은 10세 이전의 남아에서 대뇌백질에 빠르게 진행하는 탈수초현상을 보인다. 8세 된 남자 환아로 정상발달과정을 보이던 중 초등학교 입학 후에 집중장애와 산만한 모습으로 인해 주의력결핍과다활동장애로 진단받고 치료를 받았었다. 환아는 내원 8개월 전부터 말이 어눌해 지고 걸을 때 오른 발을 끌며 자주 넘어지는 모습을 보여 내원하였고 오른쪽 상, 하지의 근력이 떨어지는 양상이 관찰되었다. 검사상 부신기능저하증 소견을 보였으며 혈청 지방산 분석검사에서는 C26:0, C42:0/C22:0, C26:0/C22:0가 증가하였다. 뇌 자기공명영상에서는 T2와 FLAIR 강조영상에서 양측의 두정후두부의 백질과 소뇌의 백질에서 대칭적으로 고신호강도를 보였다. 환아는 부신백질이영양증로 진단하였고 ABCD1 유전자 분석 검사에서 새로운 c.983delT (p.Met329CysfsX7) 돌연변이가 확인되었다. X 연관 ALD는 유전자형과 표현형에 연관성이 없으며 다양한 임상양상을 보이기 때문에 환자들마다 임상증상을 잘 관찰해야 하며 향후 유전자 기능을 좀 더 파악하고 임상증상에 영향을 주는 다른 요소에 대한 연구가 필요할 것이라 사료된다.

• Animal Bioscience
• /
• 제36권1호
• /
• pp.132-143
• /
• 2023

Objective: The aim was to study the influence of cooling milk at 9℃ at the farm versus keeping it at 20℃ on Parmigiano Reggiano cheese lipolysis. Methods: A total of six cheesemaking trials (3 in winter and 3 in summer) were performed. In each trial, milk was divided continuously into two identical aliquots, one of which was kept at 9℃ (MC9) and the other at 20℃ (MC20). For each trial and milk temperature, vat milk (V-milk) and the resulting 21 month ripened cheese were analysed. Results: Fat and dry matter and fat/casein ratio were lower in MC9 V-milk (p≤0.05) than in MC20. Total bacteria, mesophilic lactic acid and psychrotrophic and lipolytic bacteria showed significant differences (p≤0.05) between the two V-milks. Regarding cheese, fat content resulted lower and crude protein higher (p≤0.05) both in outer (OZ) and in inner zone (IZ) of the MC9 cheese wheels. Concerning total fatty acids, the MC9 OZ had a lower concentration of butyric, capric (p≤0.05) and medium chain fatty acids (p≤0.05), while the MC9 IZ had lower content of butyric (p≤0.05), caproic (p≤0.01) and short chain fatty acids (p≤0.05). The levels of short chain and medium chain free fatty acids (p≤0.05) were lower and that of long chain fatty acids (p≤0.05) was higher in MC9 OZ cheese. The principal component analysis of total and free fatty acids resulted in a clear separation among samples by seasons, whereas slight differences were observed between the two different milk temperatures. Conclusion: Storing milk at 9℃ at the herd affects the chemical composition of Parmigiano Reggiano, with repercussion on lipolysis. However, the changes are not very relevant, and since the cheese can present a high variability among the different cheese factories, such changes should be considered within the "normal variations" of Parmigiano Reggiano chemical characteristics.

• Journal of Nutrition and Health
• /
• 제16권1호
• /
• pp.10-20
• /
• 1983

In order to establish tissue lipid status in animal on feeding of various dietary fat and oils, each group of rats was fed a semisynthetic diet containing 10%(w/w) mackerel oil (MO), eel oil (EO), soybean oil (SO), rapeseed oil (RO) or beef tallow (BT) for 1, 2 and 4 weeks, After each feeding period, levels of cholesterol, triglyceride and phospholipid were measured in serum. Fatty acid ${\leftarrow}$ composition was also investigated in serum and tissue lipids. Levels of total serum cholesterol were lower but HDL-cholesterol were higher in fish oil groups, which resulted in significantly higher ratio of HDL to total cholesterol in the fish oil groups. Fish oil groups, in general, also had lower levels of serum triglyceride and phospholipid than other groups, but S0 group maintained as low phospholipid levrl as fish oil groups. Fatty acid composition of dietary fat was reflected in all the tissues investigated but with varying degrees. Very long chain fatty acids, specific components exclusively found in fish oils were most well reflected in liver and relatively well in serum, whereas linoleic acid and erucic acid of SO and RO in the diet were better shown up in heart and adipose tissue. It attracted a particular attention that major proportions of long chain monoenoic acids $(C_{22:1})$ occurring both in MO and RO were detected separately in liver and heart plus adipose tissue, the result of which strongly indicates that there is a significant difference in metabolism between isomers $(C_{22:1}\;w\;11\;and\;C_{22:1}\;w\;9,\;respectively)$. It is suggested from this study that differences in lipid status as well as in the levels of serum lipids result from uniqueness in metabolism of each different fatty acid and give rise to distinguishable change in serum lipoprotein pattern, followed by diet with different fat sources.