Friday, February 5, 2010

Genes, enzymes and Dupuytren's: the alphabet name game.

A proteinase is an enzyme which breaks down proteins. Metalloproteinases (MPs) are proteinases with a molecular structure and function involves a metal atom, usually zinc. Matrix Metalloproteinases (MMPs) are MPs which act outside of cells, in the tissue matrix. Human collagenases are MMPs which break down different types of collagen. Membrane-type MMPs (MT-MMPs) are MMPs which are attached to cell membranes and protrude into the extracellular matrix. ADAMTS (A Disintegrin And Metalloproteinase with Thrombospondin Motifs) are another subgroup of MMPs. ADAMTs cut off or shed portions of proteins which protrude out of the cell wall, and are classified as sheddases (I am not making this up). TIMPs (Tissue inhibitors of Metalloproteinases) block the action of MMPs. This lecture handout outlines investigation of which genes relating to MMPs and ADAMTs are activated in osteoarthritis and Dupuytren's disease (full text: http://www.dupuytrenfoundation.org/DupPDFs/2007_Clark.pdf). In active Dupuytren's disease, five genes were involved: MMP13, which codes for collagenase 3 (breaks down type II collagen (in cartilage), and to a lesser extent types I and III collagen (in Dupuytren's cords); MMP14 codes for MMP-14, a MT-MMP collagenase which activates collagenase 3 and is activated by poor circulation; ADAMTS5, which codes for aggrecanase, an ADAMTS which breaks down cartilage; ADAMTS14, which is linked to procollagen processing; ADAMTS16, which codes for an enzyme whose function is unknown. More information on this is available here: (full text: http://www.dupuytrenfoundation.org/DupPDFs/2008_Murphy.pdf). Dupuytren's is somehow related to the way that all of these genes interact. Here's a simple question based on all of this: if Dupuytren's is related to not enough collagenase function, and zinc is needed for collagenase to function, and EDTA is an additive put in soda pop because it removes metals such as zinc, could drinking too much of your favorite carbonated beverage raise your risk for Dupuytren's?

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