Researchers at Case Western Reserve University School of Medicine have uncovered the mechanism1 that enables the enzyme2 Lecithin: retinol acyltransferase to store vitamin A--a process that is indispensable for vision. Without this information, our knowledge was inadequate3 to understand the molecular4 mechanisms5 of blindness caused by mutations in the enzyme, said Marcin Golczak, assistant professor of pharmacology at Case Western Reserve and an author of the study.The researchers hope the new information will be used to design small molecule7 therapies for degenerative eye diseases. The same enzymatic9 activity of LRAT that allows specific cells to absorb vitamin A can be used to transport small molecule drugs to the eye. These drugs would accumulate in eye tissue, lowering the effective dose and reducing risk of systemic side effects.Their work is published in the journal Nature Chemical Biology.Golczak, medical student Avery E. Sears, pharmacology instructor10 Philip D. Kiser and pharmacology chair Krzysztof Palczewski compared the function of LRAT and closely related enzymes11 that belong to N1pC/P60 family. They found that small variations in the protein sequences determine the substrate specificity--the substances on which the enzymes act--and thus govern physiological12 functions of these enzymes.LRAT regulates cellular13 uptake of vitamin A by helping14 convert it to a usable form called retinyl ester. Retinyl ester is essential for our eyes to function. Consequently, lack of LRAT leads to vitamin A deficiency and blindness.Unlike LRAT, a close relative, HRAS-like tumor15 suppressor 3, referred to as HRASLS3, does not process vitamin A, but is involved in regulation of triglycerides breakdown16 in white fat cells. Triglycerides provide an energy source for body tissues. But excess accumulation leads to obesity17 and related metabolic18 syndrome19, increasing the risk of heart disease, diabetes20 and other health problems.Mice lacking HRASLS3 gained no weight when fed high-calorie diets--even mice that were genetically21 engineered to be obese22 and lacking leptin, the hormone23 that signals mammals when theyve eaten enough food.The functions of these enzymes were known, but until now, there has been little understood about what enables the close relatives to go about their different jobs. The researchers looked at how LRAT is different from the rest of its protein family.Evolution of enzymatic activities via gene8 duplication, mutation6 and selection has led to the present diversity of metabolic capabilities, Golczak said. Our studies explain what modification24 in the cellular enzymatic machinery25 enables vertebrates to efficiently26 take up and store excess vitamin A.
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1 mechanism n.机械装置；机构，结构 参考例句： The bones and muscles are parts of the mechanism of the body.骨骼和肌肉是人体的组成部件。 The mechanism of the machine is very complicated.这台机器的结构是很复杂的。
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