Very simple, tougher cuts are well....tougher because they contain crap loads of connective tissue. When you cook something low and slow in a stew or on the bbq that connective tissue breaks down and basically melts but the proteins are not hot enough to denature and clump together, resulting in water loss and tougher meat.
Cuts from the tender parts of an animal typically do not have nearly the amount of connective tissue or fat and therefore will turn into shoe leather if cooked all the way through as there is nothing but protein and water. Very little fat and connective tissue mean that if cooked for long periods the proteins will simply conjoin and therefore toughen. This isn't so with something like beef chuck as cooking at a low temperature won't allow the protein to conjoin and the fat and tissue assist in retaining moisture. Dry heat is the only way to go for lean cuts, you want as little water loss as possible otherwise things turn ugly.
Hope that helps.
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