His207 and Asp82 most likely facilitate this process. Other studies claim that Tyr83 of subunit D is coordinated to a nearby histidine as well as the O1 carbonyl oxygen of ubiquinone. The histidine residue decreases the pKa of tyrosine, making it more suitable to donate its proton to the reduced ubiquinone intermediate. There are two distinct classes of inhibitors of complex II: those that bind in the succinate pocket and those that bind in the ubiquinone pocket. Ubiquinone type inhibitors include carboxin and thenoyltrifluoroacetone. Succinate-analogue inhibitors include the synthetic compound malonate as well as the TCA cycle intermediates, malate and oxaloacetate. Indeed, oxaloacetate is one of the most potent inhibitors of Complex II. Why a common TCA cycle intermediate would inhibit Complex II is not entirely understood, though it may exert a protective role in minimizing reverse-electron transfer mediated production of superoxide by Complex I. Atpenin 5a are highly potent Complex II inhibitors mimicking ubiquinone binding. Ubiquinone type inhibitors have been used as fungicides in agriculture since the 1960s. Carboxin was mainly used to control disease caused by basidiomycetes such as stem rusts and "Rhizoctonia" diseases. More recently, other compounds with a broader spectrum against a range of plant pathogens have been developed including boscalid, penthiopyrad and fluopyram. Some agriculturally important fungi are not sensitive towards members of the new generation of ubiquinone type inhibitors   The fundamental role of succinate-coenzyme Q reductase in the electron transfer chain of mitochondria makes it vital in most multicellular organisms, removal of this enzyme from the genome has also been shown to be lethal at the embryonic stage in mice. Mammalian succinate dehydrogenase functions not only in mitochondrial energy generation, but also has a role in oxygen sensing and tumor suppression; and, therefore, is the object of ongoing research. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of patients with Huntington's Disease, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients.