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HMGCR Gene - GeneCards | HMDH Protein | HMDH …

The biosynthesis, function and taxonomic significance ofbranched-chain fatty acids in bacteria have been reviewed ().

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Synthesis and biosynthesis Synthesis

Hu SS, Bradshaw HB, Benton VM, Chen JS, Huang SM, Minassi A, Bisogno T, Masuda K, Tan B, Roskoski R Jr, Cravatt BF, Di Marzo V, Walker JM. (2009)The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, viaconjugation of arachidonic acid with dopamine.
Prostaglandins Leukot Essent Fatty Acids. 81(4):291-301.

Biological Membranes and Membrane Transport …

Seeliger JC, Holsclaw CM, Schelle MW, Botyanszki Z, Gilmore SA, Tully SE, Niederweis M, Cravatt BF, LearyJA, Bertozzi CR. (2012). Elucidation and Chemical Modulation of Sulfolipid-1 Biosynthesis in Mycobacterium tuberculosis.
J Biol Chem. 2012 Mar 9;287(11):7990-8000.

Steroid Hormones - The Medical Biochemistry Page

Steroid producing cells through the use of multiple cholesterol supply sources discussed above maintain adequate cholesterol reserves primarily in the form of lipid droplets that enable them to quickly respond to tropic hormone stimulation with the rapid mobilization of cellular cholesterol reserves and ensuing transport to mitochondria for steroidogenesis. In adrenal and ovarian cells, cellular stores of cholesterol esters are constantly replenished by the delivery of plasma cholesterol through endocytic or selective pathway (depending on species and lipoprotein type), whereas this chore in Leydig cells, under normal physiological conditions, is mainly achieved through increased de novo cholesterol synthesis. During acute hormonal stimulation, these endogenously stored cholesterol esters are rapidly mobilized (hydrolyzed) and released free-cholesterol is efficiently transported to and within the mitochondria for its conversion to pregnenolone, the precursor of all steroid hormones. This entire process involving the intracellular cholesterol mobilization, processing and transport to the appropriate site within the mitochondria for side-chain cleavage and pregnenolone production can be broadly divided into two separate, but equally important segments: a) mobilization of cholesterol from intracellular stores, particularly from lipid droplets; b) transport of mobilized cholesterol to the outer mitochondrial membrane; and c), transfer of this cholesterol from the outer to the inner mitochondrial membrane. In the following sections, we will discuss characteristics of these three segments of intracellular cholesterol transport and also summarize current understanding about the functional roles of key proteins and factors involved in the mobilization of cellular cholesteryl esters, intracellular transport of newly released cholesterol to the outer mitochondrial membrane and its subsequent translocation to the inner mitochondrial membrane for the initiation of steroidogenesis.

The mechanism by which SR-BI mediates selective transfer of CE from the cell surface to cell interior is not clearly defined, but may require participation of accessory proteins and lipids, alterations in physicochemical characteristics of the plasma membrane and the physical forms of SR-BI itself. The entire process of "selective" cholesterol ester delivery and its subsequent utilization for steroid synthesis can be broadly divided into three distinct steps, each of which may involve multiple complex processes. The first step in the selective CE uptake is the transfer of lipoprotein-associated CE to the plasma membrane, the second step entails the translocation of CE from the plasma membrane to lipid droplets within the interior of the cell; and the third step in the process is the movement of cholesterol from intracellular lipid droplets to mitochondria for steroid hormone synthesis.

The steroid hormones are all derived from cholesterol

Leung D, Saghatelian A, Simon GM, Cravatt BF. (2006) Inactivation of N-acyl phosphatidylethanolaminephospholipase D reveals multiple mechanisms for the biosynthesis of endocannabinoids.
Biochemistry. 45(15):4720-4726.

Although adrenal, ovarian and testicular steroidogenesis is primarily under the control of tissue-specific tropic hormones (discussed below); the availability of adequate cholesterol substrate is also a critical requirement for the optimal steroid hormone production. The steroidogenic tissues and cells have the potential to obtain cholesterol for steroid synthesis from at least four potential sources (Fig. ): a) cholesterol synthesized de novo from acetate; b) cholesterol obtained from plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL); c) cholesterol-derived from the hydrolysis of stored cholesterol esters in the form of lipid droplets; and d) cholesterol interiorized from the plasma membrane. Although all three major steroidogenic organs (adrenal, testis and ovary) can synthesize cholesterol de novo under the influence of the tropic hormone, the adrenal and ovary preferentially utilize cholesterol supplied from plasma LDL and HDL via the LDL-receptor mediated endocytic pathway and SR-BI-mediated selective pathway, respectively [,-]. The use of LDL or HDL as the source of cholesterol for steroidogenesis appears to be species dependent; rodents preferentially utilize the SR-BI/selective pathway while humans, pigs and cattle primarily employ the LDL/LDL-receptor endocytic pathway to meet their cholesterol need for steroid synthesis. In contrast, testicular Leydig cells under normal physiological conditions rely heavily on the use of endogenously synthesized cholesterol for androgen (testosterone) biosynthesis [,].

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The Cravatt Lab - Scripps Research Institute

...itial phases of apoptosis. The ability of lipids to travel from the ER to mitochondria is not a novel finding. For instance, most of the enzymes of the phospholipid synthetic pathway reside in the ER =-=(42)-=-. However, some enzymes, such as phosphatidylserine decarboxylase, are located in mitochondria (43). This enzyme is critical for the formation of phosphatidylethanolamine from phosphatidylserine (43–4...

How does yeast respond to pressure? - SciELO

Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are unique in that they require cholesterol not only for membrane biogenesis, maintenance of membrane fluidity and cell signaling, but also as the starting material for the biosynthesis of steroid hormones. It is not surprising, then, that cells of steroidogenic tissues have evolved with multiple pathways to assure the constant supply of cholesterol needed to maintain optimum steroid synthesis. The cholesterol utilized for steroidogenesis is derived from a combination of sources: 1) de novo synthesis in the endoplasmic reticulum (ER); 2) the mobilization of cholesteryl esters (CEs) stored in lipid droplets through cholesteryl ester hydrolase; 3) plasma lipoprotein-derived CEs obtained by either LDL receptor-mediated endocytic and/or SR-BI-mediated selective uptake; and 4) in some cultured cell systems from plasma membrane-associated free cholesterol. Here, we focus on recent insights into the molecules and cellular processes that mediate the uptake of plasma lipoprotein-derived cholesterol, events connected with the intracellular cholesterol processing and the role of crucial proteins that mediate cholesterol transport to mitochondria for its utilization for steroid hormone production. In particular, we discuss the structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites, where P450scc (CYP11A) is localized and where the conversion of cholesterol to pregnenolone (the common steroid precursor) takes place.

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