The easiest way for you to answer your question is to compare the structures of furan and tetrahydrofuran, or to compare the structures of folate (Vitamin B3 IIRC) and tetrahydrofolate. There is a simple method to calculate the oxidation number of a carbon atoms, which might be put to good use here. You raise an interesting point about regiochemistry, but to the best of my knowledge, there is only one isomer of tetrahydrofolate that is commonly encountered biologically.