一月克劳斯
Progress Update as seen in the August 2006 PAF通讯 |
The strength of our research lies in the finding that some forms of mutant PCC are very responsive to an addition of small chemicals called chemical chaperones. These altered forms of the enzyme are not deficient in their ability to carry out the enzymatic reaction but rather in their ability to form the proper structure and assume the correct shape. The chaperone helps them to fold with a large increase in activity. We have carried out the initial experiments on normal and three mutant forms of PCC in a bacterial system in which the human enzyme can be manufactured. Later, we have used the chaperones in skin cell cultures derived from controls and propionic acidemia patients. Again, in some cases we saw large increases in PCC activity. We will continue to screen different chemicals and different mutations for their ability to yield more active PCC. The hope is that this approach can be introduced in clinical practice and help some patients to overcome their metabolic disease. The real promise is that some of the drugs, which gave us the best results, are already in use in clinical practice to treat other disorders.
PCC Website: http://www.uchsc.edu/cbs/pcc/about_pcc.htm
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分类存档: 新闻 & 公告
博士. Kraus Research studies in PA
Research Studies in Propionic Acidemia |
博士. Jan Kraus’ laboratory, Dept. of Pediatrics, University of Colorado School of Medicine – 更新 11/2011
丙酸血症 (PA) is a serious life threatening inherited disorder of metabolism. The disease is caused by deficiency of an enzyme called Propionyl CoA Carboxylase or PCC for short. PCC is a large enzyme consisting of six alpha and six beta subunits. The enzyme deficiency in turn is caused by mutations in either the PCCA or PCCB gene. My laboratory is currently supported by PAF for two projects associated with this disease. The first project deals with the determination of the mutations or inherited changes in the DNA of propionic acidemia patients from USA whose DNA samples have been submitted to the Corriell Institute. Most of these patients are members of the PA foundation. Knowing the mutations will lead to better understanding of the disease and lead to improved treatment for the affected patients. We will also determine which of the two mutations in each patient came from which parent. This determination, in turn, will enable diagnoses of mutation carrier status in both parents’ families. The second project is entitled Enzyme Replacement Therapy for Propionic Acidemia. The main objective of this research proposal is to develop a therapeutic treatment of propionic acidemia (PA) by enzyme replacement therapy. Hurdles with enzyme replacement therapy include the delivery of the active enzyme into the patient cells as well as directing it to the correct location within the cell. In the case of PCC it needs to be delivered to the mitochondria. The mitochondria are separate membrane enclosed organelles within the cell that mainly supply the energy for cells. One promising way to deliver the PCC subunits across both the cell and mitochondrial membrane is the use of what is known as the TAT peptide. This peptide can cross cellular membranes and will also take along anything that is attached to it. Thus we propose to use the TAT peptide and a mitochondrial targeting sequence as a way to deliver the functioning PCC subunits to cells. The peptide and the targeting sequence will then be removed from PCC by another enzyme already present in mitochondria. None of this work would have been possible without generous support from the Propionic Acidemia Foundation. Please give money to the foundation to support these and other studies on this devastating disease.
更新 10/2010 “This project deals with the determination of the mutations or inherited changes in the DNA of Propionic Acidmia patients from USA whose DNA samples have been submitted to the Coriell Institute. Most of thse patients are members of the PA Foundation. Knowing mutations will lead to better understanding of the disease and lead to improved treatment for the affected patients. We will also determine which of the two mutations in each patient came from which parent. This determination, in turn will enable diagnoses of mutation carrier status in both parents’ families.” |
Duke Biomarkers
Duke University
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胰腺炎
胰腺炎
Pancreatitis is an inflammation of the pancreas. It can be a complication of Propionic Acidemia. Symptoms may include vomiting, nausea, tender abdomen, and fever. Blood tests of amylase and lipase (pancreatits enzymes) will confirm a diagnosis of pancreatitis.
Molecular
Medication Links
Medication Links Carbaglu (potential medication for treatment of elevated ammonia)
Carnitine – also see Sites of Interest Supplementation Gut Motility |
肝移植
高氨血症
Hyperammonemia Links
Hyperammonemia is excess ammonia in the blood. 等离子氨的正确抽取和处理非常重要,en. For more information, see CHECKAMMONIA.com
- Emedicine, 高氨血症
- Metabolic changes associated with hyperammonemia in patients with propionic acidemia.