A major rate-limiting step in the pathway is at the level of the microsomal enzyme that catalyzes the conversion of HMG CoA to mevalonic acid, and that has been considered to be a prime target for pharmacologic intervention for several years.HMG CoA reductase occurs early in the biosynthetic pathway and is among the first committed steps to cholesterol formulation. Inhibition of this enzyme could lead to accumulation of HMG CoA, a water-soluble intermediate that is, then, capable of being readily metabolized to simpler molecules. This inhibition of reductase would lead to accumulation of lipophylic intermediates with a formal sterol ring. Lovastatin was the first specific inhibitor of HMG CoA reductase to receive approval for the treatment of hypercholesterolemia. The first breakthrough in efforts to find a potent, specific, competitive inhibitor of HMG CoA reductase occurred in 1976, when Endo et al. reported the discovery of mevastatin, a highly functionalized fungal metabolite, isolated from cultures of Penicillium citrium. Biosynthesis
The biosynthesis of lovastatin occurs via an iterative type I polyketide synthase (PKS) pathway. The six genes that encode enzymes that are essential for the biosynthesis of lovastatin are lovB, lovC, lovA, lovD, lovG, and lovF . The synthesis of dihydromonacolin L requires a total of 9-malonyl Coa . It proceeds in the PKS pathway until it reaches (E) a hexaketide, where it undergoes a Diels-Alder cycloaddition to form the fused rings. After cyclization it continues through the PKS pathway until it reaches (I) a nonaketide, which then undergoes release from LovB through the thioesterase encoded by LovG.
Thus prevention efforts include awareness campaigns to educate the public about safety measures such as seat belts and motorcycle helmets, and laws to prevent drunk and unsafe driving. Other causes of facial trauma include falls, industrial accidents, and sports injuries. Signs and symptoms
Fractures of facial bones, like other fractures, may be associated with pain, bruising, and swelling of the surrounding tissues (such symptoms can occur in the absence of fractures as well). Fractures of the nose, base of the skull, or maxilla may be associated with profuse nosebleeds. Nasal fractures may be associated with deformity of the nose, as well as swelling and bruising. Deformity in the face, for example a sunken cheekbone or teeth which do not align properly, suggests the presence of fractures. Asymmetry can suggest facial fractures or damage to nerves. People with mandibular fractures often have pain and difficulty opening their mouths and may have numbness in the lip and chin. With Le Fort fractures, the midface may move relative to the rest of the face or skull. Cause
Injury mechanisms such as falls, assaults, sports injuries, and vehicle crashes are common causes of facial trauma in children as well as adults. Blunt assaults, blows from fists or objects, are a common cause of facial injury. Facial trauma can also result from wartime injuries such as gunshots and blasts. Animal attacks and work-related injuries such as industrial accidents are other causes. Vehicular trauma is one of the leading causes of facial injuries.