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Study offers innovative profile of enzyme that aids tumor growth
October 23, 2006Findings point toward potential new treatments for ovarian, breast cancers
"Using a combination of enzyme activity and metabolite profiling, we determined that this protein-whose function was previously unknown-serves as a key regulator of a lipid signaling network that contributes to cancer," said Benjamin F. Cravatt, a Scripps Research professor and a member of its Skaggs Institute for Chemical Biology who led the study. "The heightened expression of KIAA1363 in several cancers indicates that it may be a critical factor in tumorgenesis. In addition, network components, including KIAA1363 itself, might be considered potential diagnostic markers for ovarian cancer."
This experimental method of integrated molecular profiling used in the study should also advance the functional study of metabolic enzymes in any biological system, according to Cravatt.
To date, understanding the roles of uncharacterized enzymes in cell physiology and pathology has remained problematic. Typically, the activities of enzymes have been studied in vitro using purified protein preparations. The outcome of these test-tube studies can be difficult to translate into clear characterizations of the roles that enzymes play in living systems, where these proteins generally operate within larger metabolic networks.
A primary advantage of metabolite profiling in natural biological systems is that it circumvents some of the most time-consuming steps that accompany in vitro enzyme analysis while generating data more directly related to their naturally occurring activities.
"Our hypothesis was that the determination of catalytic activities for enzymes like KIAA1363 could be done directly in living systems through the integrated application of profiling technologies that survey both the enzymatic proteome and its primary biochemical output, the metabolome," Cravatt said.
So, the team drew both on proteomics-the large-scale study of the structure and function of proteins-and metabolomics-the systematic study of cellular processes, specifically their small-molecule metabolite profiles-to begin to decipher the complex metabolic and signaling networks of cancer.
According to the study, one of the primary advantages of the functional proteomic technology employed (activity-based protein profiling) is that it can be used to identify inhibitors for uncharacterized enzymes like KIAA1363. Moreover, because inhibitors are screened against many enzymes in parallel, both potency and selectivity factors are assigned simultaneously.
The development of a selective inhibitor of KIAA1363 was possible due to the availability of an activity-based proteomics probe for this enzyme. Such probes are now available for many enzyme classes that participate in cell metabolism, so Cravatt suggests "a large swath of the enzyme proteome" could be addressed using the study's experimental strategy.
"The success of our study opens the door to assembling the full range of enzymes into both metabolic and signaling networks contributing to complex pathologies like cancer," Cravatt said. "This could lead to the discovery of new markers for diagnosis and targets for treatment."
Scripps Research Institute
To date, understanding the roles of uncharacterized enzymes in cell physiology and pathology has remained problematic. Typically, the activities of enzymes have been studied in vitro using purified protein preparations. The outcome of these test-tube studies can be difficult to translate into clear characterizations of the roles that enzymes play in living systems, where these proteins generally operate within larger metabolic networks.
A primary advantage of metabolite profiling in natural biological systems is that it circumvents some of the most time-consuming steps that accompany in vitro enzyme analysis while generating data more directly related to their naturally occurring activities.
"Our hypothesis was that the determination of catalytic activities for enzymes like KIAA1363 could be done directly in living systems through the integrated application of profiling technologies that survey both the enzymatic proteome and its primary biochemical output, the metabolome," Cravatt said.
So, the team drew both on proteomics-the large-scale study of the structure and function of proteins-and metabolomics-the systematic study of cellular processes, specifically their small-molecule metabolite profiles-to begin to decipher the complex metabolic and signaling networks of cancer.
According to the study, one of the primary advantages of the functional proteomic technology employed (activity-based protein profiling) is that it can be used to identify inhibitors for uncharacterized enzymes like KIAA1363. Moreover, because inhibitors are screened against many enzymes in parallel, both potency and selectivity factors are assigned simultaneously.
The development of a selective inhibitor of KIAA1363 was possible due to the availability of an activity-based proteomics probe for this enzyme. Such probes are now available for many enzyme classes that participate in cell metabolism, so Cravatt suggests "a large swath of the enzyme proteome" could be addressed using the study's experimental strategy.
"The success of our study opens the door to assembling the full range of enzymes into both metabolic and signaling networks contributing to complex pathologies like cancer," Cravatt said. "This could lead to the discovery of new markers for diagnosis and targets for treatment."
Scripps Research Institute
Enzymes Current Events and Enzymes News RSSCancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Researchers begin to decipher metabolism of sexual assault drug
It's a naturally occurring brain chemical with an unwieldy name: 4-hydroxybutyrate (4-HB). Taken by mouth, it can be abused or used as a date-rape drug.
The Protein Srebp2 Drives Cholesterol Formation in Prion-Infected Neuronal Cells Which May Promote Prion-Dependent Diseases
The regulating protein Srebp2 drives cholesterol formation, which prions need for their propagation, in prion-infected neuronal cells.
UCR plant scientist's research spawns new discoveries showing how crops survive drought
Breakthrough research done earlier this year by a plant cell biologist at the University of California, Riverside has greatly accelerated scientists' knowledge on how plants and crops can survive difficult environmental conditions such as drought.
New explanation for nature's hardiest life form
Got food poisoning? The cause might be bacterial spores, en extremely hardy survival form of bacteria, a nightmare for health care and the food industry and an enigma for scientists.
No-entry zones for AIDS virus
The AIDS virus inserts its genetic material into the genome of the infected cell. Scientists of the German Cancer Research Center have now shown for the first time that the virus almost entirely spares particular sites in the human genetic material in this process. This finding may be useful for developing new, specific AIDS drugs.
Largest-ever database for liver proteins may lead to treatments for hepatitis
Scientists at a group of 11 research centers in China are reporting for the first time assembly of the largest-ever collection of data about the proteins produced by genes in a single human organ.
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
Wet ethanol production process yields more ethanol and more co-products
Using a wet ethanol production method that begins by soaking corn kernels rather than grinding them, results in more gallons of ethanol and more usable co-products, giving ethanol producers a bigger bang for their buck - by about 20 percent.
Researchers identify drug candidate for treating spinal muscular atrophy
A chemical cousin of the common antibiotic tetracycline might be useful in treating spinal muscular atrophy (SMA), a currently incurable disease that is the leading genetic cause of death in infants.
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Source Naturals Daily Essential Enzymes, 500 mg, Capsules, 360 capsules by Source Naturals Enzyme supplement. Digestive aid. Bio Algin. 1st Place winner 2004 VITY awards. Each vegetarian capsule contains 500 mg of an all - vegetarian, broad spectrum blend of digestive enzymes. Contains no yeast, dairy, egg, gluten, soy or wheat. Contains no sugar, salt, preservatives, or artificial color, flavor or fragrance. (These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.) |
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Source Naturals Daily Essential Enzymes in Vegetarian Capsules, 500 mg, Capsules, 240 capsules by Source Naturals Enzyme supplement. Digestive aid. Bio Algin. Vegetarian. 1st Place winner VITY awards. Each vegetarian capsule contains 500 mg of an all - vegetarian, broad spectrum blend of digestive enzymes. Suitable for vegetarians. Contains no yeast, dairy, egg, gluten, soy or wheat. Contains no sugar, salt, preservatives, or artificial color, flavor or fragrance. (These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.) |
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Rainbow Light Advanced Enzyme System, Plant-Source, Vcaps, 180 vcaps by Rainbow Light Enzyme supplement. 50% More free. Potent & full support. Eases digestive discomfort. Plant-source enzymes. Superior VegeGuard Digestive Support with plant-source enzymes and soothing botanicals. Advanced Enzyme System formula provides: Potent, full-spectrum enzyme support - from a broad range of enzymes, including brush border enzymes to help break down all types of food including difficult-to-digest carbohydrates. Relief from digestive discomfort - with enzyme rich foods and targeted botanicals to help alleviate occasional gas and bloating. (This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.) Plant-source enzymes - to supplement enzyme-depleted foods including cooked or processed foods.... |
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Super Enzymes 180 tabs by NOW NOW Super Enzyme tablets are a comprehensive blend of enzymes that support healthy digestive functions. Bromelain, Ox Bile, Pancreatin and Papain have been formulated to optimize the breakdown of fats, carbohydrates and protein for maximum assimilation. * Picture may be of different size or flavor |
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