脂对泛醌细胞色素c还原酶的影响

用羟基磷灰石柱亲和层析法制备了高纯度的缺脂泛醌细胞色素c还原酶．脂的缺失使该酶活力丢失,部分细胞色素（约52.8％细胞色素b和82.5％细胞色素c₁）呈现还原状态．将缺脂泛醌细胞色素。还原酶与磷脂重组,可恢复其活性,同时那些呈还原状态的细胞色素也恢复到氧化态.此结果表明如此制备的缺脂泛醌细胞色素c还原酶仍保持着活力所必需的构象状态,细胞色素氧化还原状态随脂缺失的变化反映了脂与蛋白的相互作用.     

琥珀酸脱氢酶与线粒体内膜的结合——泛醌的影响

猪心肌制剂经含水4%丙酮抽提除去泛醌(Q)及部分脂后,其琥珀酸细胞色素c 还原酶活力丧失,但在反应系统中添加Q 可恢复此活力。去Q 制剂再经碱处理除去琥珀酸脱氢酶后,与新鲜制备的水溶性琥珀酸脱氢酶重组,其重组活力,包括结合的琥珀酸脱氢酶和琥珀酸细胞色素还原酶活力,与正常重组(未去除Q 的)相比,结果相似,指出Q 对琥珀酸脱氢酶与膜的结合无明显的影响,脂环境也不是重要因素。     

琥珀酸脱氢酶与线粒体内膜的结合——泛醌的影响

猪心肌制剂经含水4%丙酮抽提除去泛醌(Q)及部分脂后,其琥珀酸细胞色素c还原酶活力丧失,但在反应系统中添加Q可恢复此活力。去Q制剂再经碱处理除去琥珀酸脱氢酶后,与新鲜制备的水溶性琥珀酸脱氢酶重组,其重组活力,包括结合的琥珀酸脱氢酶和琥珀酸细胞色素还原酶活力,与正常重组(未去除Q的)相比,结果相似,指出Q对琥珀酸脱氢酶与膜的结合无明显的影响,脂环境也不是重要因素。     

日本血吸虫琥珀酸氧化酶的研究

应用測压法和分光光度法証明了日本血吸虫含有琥珀酸氧化酶,琥珀酸脫氫酶,琥珀酸-細胞色素c还原酶和細胞色素氧化酶等完整系統。血吸虫的琥珀酸氧化酶活力与細胞色素c浓度有关,浓度增加,酶活力上升,在0.4×10~(-5)—2×10~(-5)M之間与酶活力成直綫关系。酶活力与磷酸盐浓度亦有一定关系,浓度愈低,酶活力愈強。在酶作用的最适条件下(琥珀酸鈉,0.02M;細胞色素c,2×10~(-5)M;磷酸盐緩冲液,0.01M,pH7.4)測定合抱成虫匀浆的酶活力,結果为:氧耗量Qo_2=30.3微升/小时/毫克氮量;琥珀酸耗量Q_S=322微克/小时/毫克氮量;延胡索酸产生量Q_F=157微克/小时/毫克氮量。当雌雄虫分別測定时,在等氮量基础上,雌虫酶活力比雄虫高。丙二酸鈉,二乙基二硫代氨基甲酸鈉(銅試剂)和氰化物都能強烈地抑制琥珀酸氧化酶活力。治疗血吸虫病常用的几种銻剂在2×10~(-3)M时,体外試驗,对此酶活力无明显的抑制作用。此外,氰化物除抑制細胞色素氧化酶外,还能抑制琥珀酸脫氫酶(用甲烯蓝方法測定)。与細胞色素c相似,維生素K_3亦能刺激匀浆的呼吸。此外,我們发現了日本血吸虫匀浆經过加热处理后,可以分离出一种耐热的“还原物貭”,对細胞色素c有化学的还原作用。本文还討論了血吸虫琥珀酸的代謝途径和細胞色素系統在呼吸鏈中可能占有重要地位。     

酿酒酵母酚类抑制物耐受性脂质组学研究

通过脂质组学分析方法从细胞膜磷脂分布方面探究适应进化酿酒酵母酚酸耐受性机制。主要利用高效液相色谱-质谱(LC-MS)对酚酸胁迫下适应进化菌株和原始菌株脂质成分检测并进行统计学比较分析。检测出565种脂质代谢物,包含细胞膜磷脂185种。相比初始菌株,适应进化菌株细胞膜中磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)和磷脂酰肌醇(PI)类磷脂分子相对含量增加,含有长链(C32-C36)和双不饱和脂酰链的磷脂分子含量增加。统计学分析表明显著性差异磷脂分子主要为含有长链不饱和脂酰链的PC和PE类磷脂分子。推测适应进化菌株通过膜磷脂重塑提高细胞膜完整性,对酚类抑制物起到选择性屏障作用,从而保持细胞活性。     

脂类也能形成螺旋状结构

北京医学院生物物理教研室林克椿教授1981年在美国Stanford大学工作期间,发现在Ca~(2 )的作用下,硷性磷脂(心磷脂,CL)和磷脂酰胆硷(PC)的混合物可形成折叠紧凑的单螺旋状和双螺旋状脂质体;并提出用Ca~(2 )促进的膜与膜之间接触解释此现象。作者将含有克分子比为37∶63的CL和二肉蔻酰磷脂酰胆硷(DMPC)双相混合物的氯仿-甲醇溶液蒸     

乳腺癌转移中的磷脂酰胆碱和溶血磷脂酰胆碱分析（英文）

我们以前曾报道花生四烯酸(arachidonic acid,AA)代谢产物可以促进乳腺癌细胞增殖和迁移.为了进一步寻找维持高转移乳腺癌细胞中AA高水平代谢的内源机制,深入探求AA代谢促进乳腺癌细胞转移的分子机理,我们应用HPLC/ESI/MSn技术检测和分析了乳腺癌MCF-7和高转移乳腺癌LM-MCF-7细胞中溶血磷脂酰胆碱(lysophosphatidylcholines,Lyso PCs)和磷脂酰胆碱(phosphatidylcholines,PCs)的成分和含量.发现了10种Lyso PC的含量在LM-MCF-7细胞中显著高于MCF-7细胞,有6种PC可水解产生AA,它们在LM-MCF-7细胞中的含量显著低于MCF-7细胞,提示这些溶血磷脂含量的升高和磷脂含量的降低可能与乳腺癌转移相关.在LM-MCF-7细胞中,COX-2抑制剂吲哚美辛(indomethacin,Indo)和LOX抑制剂(nordihydroguaiaretic acid,NDGA)共同作用可明显下调c PLA2的活性,应用HPLC-ESI-MSn技术比较c PLA2活性下调前后LM-MCF-7细胞中Lyso PC和PC含量的变化,发现其中4种PC可被c PLA2水解产生AA.还发现,细胞内Lyso PC与PC的比值可以反映c PLA2的活性.通过以上研究进一步证实了由c PLA2活性调节的AA释放及代谢对乳腺癌转移具有重要作用.     

我国健康成人红细胞膜脂类的脂酸组成

 本文采用双向簿层层析分离红细胞膜脂类,继以毛细管气相色谱法分析其脂酸含量,检测了15名我国健康成人红细胞膜脂类的脂酸摩尔百分组成。结果表明:各脂类中,脂酸的类别基本相同,但其含量组成相差甚远。如磷脂酰乙醇胺(PE)富含C_(20:4);磷脂酰胆碱(PC)富含C_(18:2);神经鞘磷脂(SM)主要含C_(16:0);磷脂酰丝氨酸(PS)主要含C_(18:0);而以红细胞糖苷脂(GL)中脂酸含量最少。膜总脂中饱和脂酸与不饱和脂酸的含量大致相等,胆碱磷脂(PC+SM)的脂酸饱和度则明显高于氨基磷脂(PE+PS)。     

血红素对一些黄酶的抑制作用

血红素对一些黄酶都具有强烈的抑制作用,并且血红素过老化以后对一些黄酶活力的抑制程度因受体不同而有显著差别。在相同的抑制剂浓度下,心肌制剂琥珀酸及NADH氧化酶系中以氧气、细胞色素c和PMS为受体时的活力没有影响,但对以正铁氰化钾、DGPIP和细胞色素b为受体时的活力则有明显抑制。对水溶性琥珀酸脱氢酶、黄递酶和NADH-细胞色素c还原酶以不同受体进行反应时的抑制情况也与上述结果相似,说明抑制作用点直接与琥珀酸脱氢酶及NADH脱氢酶有关。老化血红素对黄嘌呤氧化酶的抑制作用不同,它不影响DCPIP为受体时的活力而却抑制细胞色素c的还原。老化血红素对胆硷氧化酶系及α-甘油磷酸氧化酶系的抑制行为与NADH及琥珀酸氧化酶系相似,看来胆硷和α-甘油磷酸脱氢酶可能也都是黄酶。老化血红素对以上黄酶的抑制都是可逆的,并且从检查6个酶系的结果知道这些抑制皆属竞争性类型。     

活体内磷脂酰胆碱替代磷脂酰乙醇胺影响E.coli细胞的功能

【目的】通过磷脂酰胆碱(PC)阳性大肠杆菌菌株与磷脂酰乙醇胺(PE)阳性野生型和PE阴性突变型菌株比较,并用PC+PE+双阳性菌株佐证,从细菌形态、生理生化以及巨噬细胞对细菌的吞噬作用等方面探讨活体内磷脂酰胆碱能否替代磷脂酰乙醇胺。【方法】光学和电子显微镜观察细菌形态和结构;不同条件培养细菌并使用分光光度计测定OD600值,评估细菌的生长情况;使用SDS-PAGE和2-D电泳法测定细菌间质蛋白组分;用小鼠RAW264.7巨噬细胞系检测细菌的粘附和吞噬作用。【结果】与短棒状的PE+野生型细菌AD93/pDD72相比,PC+细菌AD93/ptac67中仍有25%丝状体;与PE-突变体AD93一样,PC+细菌AD93/ptac67仍需要添加二价离子Mg2+或Ca2+才能生长;与野生型AD93/pDD72相比,PC+细菌AD93/ptac67的周质蛋白组分、粘附率与相对吞噬效率呈现明显的差异;与野生型细菌Top10/ptac85相比,PE+PC+双阳性细菌Top10/ptac66的细胞壁外层、抗逆性和周质蛋白组分也显示差别。【结论】在活体内,膜磷脂中PC替代PE不能使PE-突变体细胞的功能完全恢复至野生型状态,PE和PC在功能上存在明显的差别,两者在功能上不能相互替代。     

Effect of modification of storage atmosphere on phospholipids and ultrastructure of cauliflower mitochondria

Differences in mitochondrial membrane composition and ultrastructure were studied after storage of cauliflower ( Brassica oleracea , L., Botrytis group) for 5 days at 25°C in air or under controlled atmospheres: 3% O₂, 21% O₂+ 15% CO₂ or 3% O₂+ 15% CO₂. In air, postharvest senescence involved a 20% decrease in mitochondrial phospholipid content. A large reduction in the relative abundance of phosphati-dylcholine (PC) and in the degree of unsaturation of PC and phosphatidyl ethanolamine (PE) was observed. However, the degree of unsaturation increased in cardiolipin (CL). Storage under 3% O₂ did not prevent phospholipid breakdown. Low O₂ prevented the relative decrease in PC observed during storage in air and the loss of linoleic acid from PC, but not from PE. This relative protection offered by the low O₂ atmosphere was lost under 3% O₂+ 15% CO₂. The high CO₂ atmospheres caused twice as much loss in phospholipids as that observed during storage in air. Extensive loss of mitochondrial protein, a marked decrease in phospholipid to protein ratio, and electron micrograph observations suggest structural alterations in the presence of high CO₂.     

The effect of adriamycin and duramycin on calcium translocation in liposome systems modeled on the inner mitochondrial membrane

Adriamycin (doxorubicin, AdM) is a potent antineoplastic agent which binds specifically and with high affinity to the acidic phospholipid cardiolipin (CL) [Goormaghtigh et al. (1980) Biochim. Biophys. Acta 597, 1]. Duramycin (DM), a polypeptide antibiotic, has been reported to interact selectively with phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol [Navarro et al. (1985) Biochemistry 24, 4645]. The selectivity of DM-PE interaction was confirmed. AdM and DM were then used to explore the roles of CL and PE in Ca2+ translocation in a phosphatidylcholine (PC)/PE/CL liposome system modeled on the inner mitochondrial membrane with the following results: (i) AdM (100-400 microM) altered Ca2+ uptake by PC/PE/CL (4/4/1, mol/mol) liposomes in a concentration-dependent fashion which varied with temperature, external Ca2+ concentration, and liposome PE content. (ii) Addition of AdM was qualitatively equivalent to increasing temperature, Ca2+ concentration, or liposome PE content, and cooperative interactions among these parameters were observed. An increase in any one factor generally enhanced Ca2+ uptake; simultaneous increases in several factors inhibited uptake. (iii) Inhibition of Ca2+ uptake was correlated with efflux of Arsenazo III. (iv) Ca2+ uptake by PC/PE/CL liposomes is biphasic [Kester and Sokolove (1989) Biochim. Biophys. Acta 980, 127]. DM suppressed the PE-dependent slow phase and stimulated the PE-independent initial phase. Ca2+ uptake by PC/PE/CL liposomes in the presence of DM resembled uptake by PC/CL liposomes. These data confirm the ability of PE to enhance the slow, highly temperature-dependent component of CL-mediated Ca2+ translocation and suggest that this process is sensitive to lipid phase behavior.     

Changes in phospholipid composition and phospholipase D activity during the differentiation of Physarum polycephalum

Changes in phospholipid composition and phospholipase D activity were observed during a differentiation from haploid myxoamoebae to diploid plasmodia of a true slime mold, Physarum polycephalum. In the amoeboid stage, the main components of phospholipid fraction were phosphatidylethanolamine (PE, 43.3%), phosphatidylcholine (PC, 28.8%) and phosphatidylinositol (PI, 8.0%), but in the plasmodial stage, PC was dominant (40.7%) and other main components were PE (31.5%) and phosphatidic acid (PA, 11.0%). The specific activity of phospholipase D in the plasmodia was 5.7-times higher than that in the myxoamoebae when measured in the presence of Ca2+ at the alkaline pH. In the amoeboid stage, phospholipase A activity (A1 or A2) was detected at the alkaline pH with Ca2+. Phospholipase D activity in the plasmodia was characterized: pH optimum was 6.0; Ca2+ was required for the reaction and Ba2+ could substitute partly for Ca2+; PE was the best substrate for the hydrolytic activity and PC and PI were not appreciably hydrolyzed; and all detergents tested inhibited the enzyme activity.     

Lipid peroxidation and phospholipase A2 activity in liposomes composed of unsaturated phospholipids: a structural basis for enzyme activation

The effect of lipid peroxidation on membrane structure and phospholipase A2 activity was studied using liposomes composed of bovine liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The phospholipids were mixed at set ratios and sonicated to yield small unilamellar vesicles. The liposome preparations were subjected to lipid peroxidation as induced by cumene hydroperoxide and hematin. Under these conditions, a sharp increase in lipid peroxidation was noted over a 30 min incubation period and was accompanied by loss of polyunsaturated fatty acids (PUFA). Liposomes enriched in PE were most extensively peroxidized with a preferred oxidation of this phospholipid. The extent of PC oxidation was also greater in liposomes containing the largest proportions of PE. Analysis of liposome anisotropy, via steady-state fluorescence polarization of diphenylhexatriene indicated that progressive increases in either PE content or the level of lipid peroxidation increased the apparent microviscosity of the vesicles. Moreover, lipid peroxidation increased anisotropy more effectively than variations in the ratios of PE vs. PC. Thus, peroxidation of 5-10% of the phospholipids produced the same anisotropy increase as a 20% increase in the ratio of PE vs. PC. Analysis of vesicle turbidity suggested that fusion was also more readily achieved through lipid peroxidation. When liposomes were incubated with 0.4 U/ml of snake venom phospholipase A2, a direct correlation was found between the degree of lipid peroxidation and the extent of phospholipid hydrolysis. The more unsaturated phospholipid, PE, was most extensively hydrolyzed following peroxidation. Increasing the proportion of PE also resulted in more extensive phospholipid hydrolysis. These findings indicate that lipid peroxidation produces a general increase in membrane viscosity which is associated with vesicle instability and enhanced phospholipase A2 attack. A structural basis for membrane phospholipase A2 activation as a consequence of lipid peroxidation is discussed in light of these findings.     

Low-salt diet alters the phospholipid composition of rat colonocytes

The effect of low-salt diet on phospholipid composition and remodeling was examined in rat colon which represents a mineralocorticoid target tissue. To elucidate this question, male Wistar rats were fed a low-salt diet and drank distilled water (LS, low-salt group) or saline instead of water (HS, high-salt group) for 12 days before the phospholipid concentration and fatty acid composition of isolated colonocytes were examined. The dietary regimens significantly influenced the plasma concentration of aldosterone which was high in LS group and almost zero in HS group. Plasma concentration of corticosterone was unchanged. When expressed in terms of cellular protein content, a significantly higher concentration of phospholipids was found in LS group, with the exception of sphingomyelin (SM) and phosphatidylserine (PS). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accounted for more than 70% of total phospholipids in both groups. A comparison of phospholipid distribution in LS and HS groups demonstrated a higher percentage of PE and a small, but significant, decrease of PC and SM in LS group. The percentage of phosphatidylinositol (PI), PS and cardiolipin (CL) were not affected by mineralocorticoid treatment. With respect to the major phospholipids (PE, PC), a higher level of n-6 polyunsaturated fatty acids (PUFA) and lower levels of monounsaturated fatty acids were detected in PC of LS group. The increase of PUFA predominantly reflected an increase in arachidonic acid by 53%. In comparison to the HS group, oleic acid content was decreased in PC and PE isolated from colonocytes of the LS group. Our data indicate that alterations in phospholipid concentration and metabolism can be detected in rats with secondary hyperaldosteronism. The changes in phospholipid concentration and their fatty acid composition during fully developed effect of low dietary Na+ intake may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.     

Phospholipid Composition and Metabolism of Micrococcus denitrificans

The phospholipid composition of Micrococcus denitrificans was unusual in that phosphatidyl choline (PC) was a major phospholipid (30.9%). Other phospholipids were phosphatidyl glycerol (PG, 52.4%), phosphatidyl ethanolamine (PE, 5.8%), an unknown phospholipid (5.3%), cardiolipin (CL, 3.2%), phosphatidyl dimethylethanolamine (PDME, 0.9%), phosphatidyl monomethylethanolamine (PMME, 0.6%), phosphatidyl serine (PS, 0.5%), and phosphatidic acid (0.4%). Kinetics of ³²P incorporation suggested that PC was formed by the successive methylations of PE. Pulse-chase experiments with pulses of ³²P or acetate-1-¹⁴C to exponentially growing cells showed loss of isotopes from PMME, PDME, PS, and CL with biphasic kinetics suggesting the same type of multiple pools of these lipids as proposed in other bacteria. The major phospholipids, PC, PG, and PE, were metabolically stable under these conditions. The fatty acids isolated from the complex lipids were also unusual in being a simple mixture of seven fatty acids with oleic acid representing 86% of the total. Few free fatty acids and no non-extractable fatty acids associated with the cell wall or membrane were found.     

Effects of age-dependent or liposome-induced alterations in the phospholipid composition on sphingomyelin biosynthesis in rat liver microsomal and plasma membranes.

1. The effects of age-dependent or liposome-induced alterations in the phospholipid composition of rat liver plasma and microsomal membranes on the phosphatidylethanolamine:ceramide-phosphoethanolamine (PE:Cer-PEt) and phosphatidylcholine:ceramide-phosphocholine (PC:Cer-PCh) transferase activities were studied. 2. In all cases under study the PE:Cer-PEt transferase activity was found to be several times higher than that of PC:Cer-PCh transferase in both plasma and microsomal rat liver membranes. 3. The presence of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in plasma membranes was observed to enhance the PE:Cer-PEt transferase activity, while phosphatidylserine (PS) inhibited it.     

Enhanced phospholipase B activity and alteration of phospholipids and neutral lipids in Saccharomyces cerevisiae exposed to N-nitrosonornicotine

A tobacco-specific nitrosamine (TSNA), N-nitrosonornicotine (NNN), is a potent carcinogen present in cigarette smoke, and chronic exposure to it can lead to pulmonary cancer. NNN causes changes in phospholipid metabolism and the mechanism is yet to be elucidated. Exposure of Saccharomyces cerevisiae to 50 μM NNN leads to a substantial decrease in phosphatidylserine (PS) by 63%, phosphatidylcholine (PC) by 42% and phosphatidylethanolamine (PE) by 36% with a concomitant increase in lysophospholipids (LPL) by 25%. The alteration in phospholipid content was dependent on increasing NNN concentration. Reduced phospholipids were accompanied with increased neutral lipid content. Here we report for the first time that NNN exposure, significantly increases phospholipase B (PLB) activity and the preferred substrate is PC, a major phospholipid responsible for a series of metabolic functions. Furthermore, NNN also promotes the alteration of fatty acid (FA) composition; it increases the long chain fatty acid (C18 series) in phospholipids specifically phosphatidylethanolamine (PE) and PS; while on the contrary it increases short chain fatty acids in cardiolipin (CL). NNN mediated degradation of phospholipids is associated with enhanced PLB activity and alteration of phospholipid composition is accompanied with acyl chain remodelling. Understanding the altered phospholipid metabolism produced by NNN exposure is a worthwhile pursuit because it will help to understand the toxicity of tobacco smoke.     

Depletion of phosphatidylcholine in yeast induces shortening and increased saturation of the lipid acyl chains: evidence for regulation of intrinsic membrane curvature in a eukaryote

To study the consequences of depleting the major membrane phospholipid phosphatidylcholine (PC), exponentially growing cells of a yeast cho2opi3 double deletion mutant were transferred from medium containing choline to choline-free medium. Cell growth did not cease until the PC level had dropped below 2% of total phospholipids after four to five generations. Increasing contents of phosphatidylethanolamine (PE) and phosphatidylinositol made up for the loss of PC. During PC depletion, the remaining PC was subject to acyl chain remodeling with monounsaturated species replacing diunsaturated species, as shown by mass spectrometry. The remodeling of PC did not require turnover by the SPO14-encoded phospholipase D. The changes in the PC species profile were found to reflect an overall shift in the cellular acyl chain composition that exhibited a 40% increase in the ratio of C16 over C18 acyl chains, and a 10% increase in the degree of saturation. The shift was stronger in the phospholipid than in the neutral lipid fraction and strongest in the species profile of PE. The shortening and increased saturation of the PE acyl chains were shown to decrease the nonbilayer propensity of PE. The results point to a regulatory mechanism in yeast that maintains intrinsic membrane curvature in an optimal range.     

Age-related changes in mitochondrial membrane composition of rainbow trout (Oncorhynchus mykiss) heart and brain

Membrane composition, particularly of mitochondria, could be a critical factor by determining the propagation of reactions involved in mitochondrial function during periods of high oxidative stress such as rapid growth and aging. Considering that phospholipids not only contribute to the structural and physical properties of biological membranes, but also participate actively in cell signaling and apoptosis, changes affecting either class or fatty acid compositions could affect phospholipid properties and, thus, alter mitochondrial function and cell viability. In the present study, heart and brain mitochondrial membrane phospholipid compositions were analyzed in rainbow trout during the four first years of life, a period characterized by rapid growth and a sustained high metabolic rate. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and phospholipid class compositions of heart and brain mitochondria, and fatty acid compositions of individual phospholipid classes were determined. Rainbow trout heart and brain mitochondria showed different phospholipid compositions (class and fatty acid), likely related to tissue-specific functions. Furthermore, changes in phospholipid class and fatty acid compositions with age were also tissue-dependent. Heart mitochondria had lower proportions of cardiolipin (CL), phosphatidylserine (PS) and phosphatidylinositol, and higher levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with age. Heart mitochondrial membranes became more unsaturated with age, with a significative increase of peroxidation index in CL, PS and sphingomyelin (SM). Therefore, heart mitochondria became more susceptible to oxidative damage with age. In contrast, brain mitochondrial PC and PS content decreased in 4-year-old animals while there was an increase in the proportion of SM. The three main phospholipid classes in brain (PC, PE and PS) showed decreased n-3 polyunsaturated fatty acids, docosahexaenoic acid and peroxidation index, which indicate a different response of brain mitochondrial lipids to rapid growth and maturation.