Assignments got your hair on fire?

Douse the flames with our full-range writing service!

Experienced academic writing professionals are at your fingertips. Use this handy tool to get a price estimate for your project.

Cholesterol precursors: More than mere markers of biosynthesis

Smith-Lemli-Opitz syndrome (SLOS; see ref. ) is due to mutation of the gene coding for 7-dehydrocholesterol reductase (DHCR7). DHCR7 reduces the Δ7 double bond in 7-dehydrocholesterol (7-DHC) to yield cholesterol in the final step of cholesterol synthesis. Impaired DHCR7 activity causes an accumulation of 7-DHC and cholesterol deficiency. Clinical manifestations of SLOS (Figure ) are variable, and the phenotypic spectrum is broad. Severely affected infants have multiple congenital anomalies and devastating neurological impairment. In contrast, mild SLOS combines learning and autistic-like behavioral problems with minor physical anomalies. Typical craniofacial findings include microcephaly; ptosis; a short, upturned nose; and micrognathia. Cleft palate occurs in approximately half of the patients. Limb anomalies include short thumbs, postaxial polydactyly, and 2-3 toe syndactyly. SLOS is a relatively common genetic disorder. The clinical incidence has been estimated to be on the order of 1 in 20,000 to 1 in 60,000. However, the carrier frequency for SLOS mutations suggests an incidence on par with more well-known genetic disorders, such as phenylketonuria (1 in 14,000) and osteogenesis imperfecta (1 in 20,000).

AB - Previous studies have demonstrated that as the density of cultured oral epithelial cells increases, there is a concomitant increase in phospholipids and cholesterol ester synthesis and a decrease in that of cholesterol and sterol precursors. Other studies have suggested that the effects of exogenous cholesterol sulfate may be similar to growth responses and influence metabolic steps related to cell density. To further examine this possibility, in the present study lipid synthesis was monitored in hamster cheek pouch epithelial cells in cultures established at different cells densities and in the presence of varying amounts of exogenous cholesterol sulfate. Cell [ 14C]acetate incorporation into lipids was measured in cultures established at four densities ranging from very subconfluent to very dense (postconfluent) in two media, Dulbecco's modified Eagle's medium (DMEM) with 5% fetal bovine serum and KSFM, a non-serum containing keratinocyte medium. Results indicated that the relative proportion of radiolabel incorporated into different lipid classes changed with cell density. In DMEM, the percentage of radiolabel incorporated into total phospholipids and fatty acids increased significantly with increasing cell density whereas percent incorporation into cholesterol, sterol precursors, and cholesterol esters significantly decreased. In KSFM cultures, proportionate phospholipids labeling was significantly increased in more dense cultures whereas cholesterol and cholesterol esters labeling was significantly decreased. In subconfluent and confluent cultures exposed to 10 or 25 μM cholesterol sulfate, the relative proportions of phospholipid labeling also increased significantly compared to dimethyl sulfoxide (solvent) controls, whereas sterol precursors, fatty acids, and cholesterol esters labeling was signifcantly decreased. These results indicate that cholesterol sulfate can affect cellular lipid synthesis in a manner similar to that which occurs with increasing cell density, and strengthen the hypothesis that cholesterol sulfate may regulate lipid metabolic pathways related to growth and differentiation.

Cholesterol synthesis is estimated to require ≈30 separate reactions involving different ..

For example, the synthesis of phospholipids requires acetyl CoA, ..

Previous studies have demonstrated that as the density of cultured oral epithelial cells increases, there is a concomitant increase in phospholipids and cholesterol ester synthesis and a decrease in that of cholesterol and sterol precursors. Other studies have suggested that the effects of exogenous cholesterol sulfate may be similar to growth responses and influence metabolic steps related to cell density. To further examine this possibility, in the present study lipid synthesis was monitored in hamster cheek pouch epithelial cells in cultures established at different cells densities and in the presence of varying amounts of exogenous cholesterol sulfate. Cell [ 14C]acetate incorporation into lipids was measured in cultures established at four densities ranging from very subconfluent to very dense (postconfluent) in two media, Dulbecco's modified Eagle's medium (DMEM) with 5% fetal bovine serum and KSFM, a non-serum containing keratinocyte medium. Results indicated that the relative proportion of radiolabel incorporated into different lipid classes changed with cell density. In DMEM, the percentage of radiolabel incorporated into total phospholipids and fatty acids increased significantly with increasing cell density whereas percent incorporation into cholesterol, sterol precursors, and cholesterol esters significantly decreased. In KSFM cultures, proportionate phospholipids labeling was significantly increased in more dense cultures whereas cholesterol and cholesterol esters labeling was significantly decreased. In subconfluent and confluent cultures exposed to 10 or 25 μM cholesterol sulfate, the relative proportions of phospholipid labeling also increased significantly compared to dimethyl sulfoxide (solvent) controls, whereas sterol precursors, fatty acids, and cholesterol esters labeling was signifcantly decreased. These results indicate that cholesterol sulfate can affect cellular lipid synthesis in a manner similar to that which occurs with increasing cell density, and strengthen the hypothesis that cholesterol sulfate may regulate lipid metabolic pathways related to growth and differentiation.

Xu G, Servatius RJ, Shefer S, et al. (1998) Relationship between abnormal cholesterol synthesis and retarded learning in rats. Metabolism, Clinical and Experimental 47 (7): 878–882.

Regulation of Cholesterol and Fatty Acid Synthesis

Xu G, Salen G, Shefer S, et al. (1995) Treatment of the cholesterol biosynthetic defect in Smith–Lemli–Opitz syndrome reproduced in rats by BM 15.766. Gastroenterology 109 (4): 1301–1307.

Inborn errors of cholesterol synthesis cause human malformation syndromes, including Smith-Lemli-Opitz syndrome, lathosterolosis, desmosterolosis, X-linked dominant chondrodysplasia punctata type 2, and congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Because adequate cholesterol is not transported across the placenta, low cholesterol and elevated sterol precursor levels are present during embryogenesis. It has been debated whether the malformations result from low cholesterol or the buildup of sterol precursors. In this issue of the JCI, Engelking et al. provide evidence that sterol precursor accumulation plays a pivotal role in the genesis of facial malformations (see the related article beginning on page 2356).

Versatile Services that Make Studying Easy
We write effective, thought-provoking essays from scratch
We create erudite academic research papers
We champion seasoned experts for dissertations
We make it our business to construct successful business papers
What if the quality isn’t so great?
Our writers are sourced from experts, and complete an obstacle course of testing to join our brigade. Ours is a top service in the English-speaking world.
How do I know the professor won’t find out?
Everything is confidential. So you know your student paper is wholly yours, we use CopyScape and WriteCheck to guarantee originality (never TurnItIn, which professors patrol).
What if it doesn’t meet my expectations?
Unchanged instructions afford you 10 days to request edits after our agreed due date. With 94% satisfaction, we work until your hair is comfortably cool.
Clients enjoy the breezy experience of working with us
Click to learn our proven method

Cholesterol synthesis steps and regulation - SlideShare


Biosynthesis of Cholesterol | The Biochemistry Questions …

Tint GS, Irons M, Elias ER, et al. (1994) Defective cholesterol biosynthesis associated with the Smith–Lemli–Opitz syndrome. New England Journal of Medicine 330: 107–113.

8/18/2008 · Biosynthesis of Cholesterol

Wassif CA, Krakowiak PA, Wright BS, et al. (2005) Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith–Lemli–Opitz syndrome fibroblasts. Molecular Genetics and Metabolism 85 (2): 96–107. Epub February 5.

Progesterone Inhibits Cholesterol Biosynthesis in …

Rossi M, Vajro P, Iorio R, et al. (2005) Characterization of liver involvement in defects of cholesterol biosynthesis: long‐term follow‐up and review. American Journal of Medical Genetics 132 (2): 144–151.

Endogenous synthesis of cholesterol in the human …

Krakowiak PA, Wassif CA, Kratz L, et al. (2003) Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5‐desaturase deficiency. Human Molecular Genetics 12 (13): 1631–1641.

Endogenous synthesis of cholesterol in the human ..

N2 - Previous studies have demonstrated that as the density of cultured oral epithelial cells increases, there is a concomitant increase in phospholipids and cholesterol ester synthesis and a decrease in that of cholesterol and sterol precursors. Other studies have suggested that the effects of exogenous cholesterol sulfate may be similar to growth responses and influence metabolic steps related to cell density. To further examine this possibility, in the present study lipid synthesis was monitored in hamster cheek pouch epithelial cells in cultures established at different cells densities and in the presence of varying amounts of exogenous cholesterol sulfate. Cell [ 14C]acetate incorporation into lipids was measured in cultures established at four densities ranging from very subconfluent to very dense (postconfluent) in two media, Dulbecco's modified Eagle's medium (DMEM) with 5% fetal bovine serum and KSFM, a non-serum containing keratinocyte medium. Results indicated that the relative proportion of radiolabel incorporated into different lipid classes changed with cell density. In DMEM, the percentage of radiolabel incorporated into total phospholipids and fatty acids increased significantly with increasing cell density whereas percent incorporation into cholesterol, sterol precursors, and cholesterol esters significantly decreased. In KSFM cultures, proportionate phospholipids labeling was significantly increased in more dense cultures whereas cholesterol and cholesterol esters labeling was significantly decreased. In subconfluent and confluent cultures exposed to 10 or 25 μM cholesterol sulfate, the relative proportions of phospholipid labeling also increased significantly compared to dimethyl sulfoxide (solvent) controls, whereas sterol precursors, fatty acids, and cholesterol esters labeling was signifcantly decreased. These results indicate that cholesterol sulfate can affect cellular lipid synthesis in a manner similar to that which occurs with increasing cell density, and strengthen the hypothesis that cholesterol sulfate may regulate lipid metabolic pathways related to growth and differentiation.

What are the precursors for synthesis of the eicosanoids

Hoffman GF, Gibson KM, Brandt IK, et al. (1986) Mevalonic aciduria: an inborn error of cholesterol and nonsterol isoprene biosynthesis. New England Journal of Medicine 314: 1610–1614.

precursors of cholesterol synthesis…

Cooper MK, Wasif CA, Krakowiak PA, et al. (2003) A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis. Nature Genetics 33: 508–513.

89%
of clients claim significantly improved grades thanks to our work.
98%
of students agree they have more time for other things thanks to us.
Clients Speak
“I didn’t expect I’d be thanking you for actually improving my own writing, but I am. You’re like a second professor!”