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carbon to form DmethylmalonylCoA, catalyzed by propionylCoA carboxylase. ? The DmethylmalonylCoA is then epimerized to the Lisomer by the action of an epimerase. ? The LmethylmalonylCoA is then converted to succinylCoA by an intramolecular rearrangement via free radical intermediates, with the catalysis of methylmalonylCoA mutase, using 5’deoxyadenosylcobalamin (or coenzyme B12) as a coenzyme. ? Coenzyme B12 enzymes act in intramolecular rearrangements, methylation, and reduction of ribonucleotides to deoxynucleotides. ? Pernicious anemia (惡性貧血 ) is caused by a failure to absorb vitamin B12, which may in turn be caused by a deficiency of the intrinsic factor, a 59 kD glycoprotein needed for vitamin B12 absorption. ? Vitamin B12 is synthesized by a few intestinal bacteria (not plants). 3D structure of coenzyme B12 and penicillin 11. The rate of boxidation in mitochondria is limited by the entering rate of fatty acylCoA ? Fatty acylCoA in the cytosol can enter mitochondria for oxidative degradation or be converted to triacylglycerol in the cytosol when excess glucose is present that can not be oxidized or stored as glycogen and is converted into fatty acids for storage. ? The key regulatory protein is carnitine acyltransferase I, which is inhibited by malonylCoA, the first intermediate for fatty acid synthesis from acetylCoA. Coordinated regulation of fatty acid synthesis and breakdown 12. Fatty acid oxidation also occurs in peroxisomes (glyoxysomes) ? Peroxisome is the principle anelle in which fatty acids are oxidized in plant cells. ? Also via the fourstep b oxidation pathway, but the electrons collected by FAD are directly passed to O2, producing the harmful H2O2, which is immediately converted to H2O and O2 . ? Energy released is dissipated as heat, not conserved in ATP. Comparison of boxidation in mitochondrion and in peroxisome/glyoxysome ? The acetylCoA produced in animal peroxisomes is transported into cytosol, where it is used in the synthesis of cholesterol and other metabolites. ? The acetylCoA produced in plant peroxisomes/ glyoxysomes (especially in germinating seeds) is converted to succinate via the glyoxylate cycle, and then to glucose via gluconeogenesis. Triacylglycerols as glucose source in seeds The boxidation enzymes in mitochondria and peroxisomes are anized differently: being separate enzymes in mitochondria (as in grampositive bacteria) and one plex in peroxisomes (as in gramnegative bacteria) Bound to the inner mitochondrial membrane 13. AcetylCoA in liver can be converted to ketone bodies when carbohydrate supply is not optimal ? Under fasting or diabetic conditions, oxaloacetate concentration in hepatocyte will be low: the rate of glycolysis is low (thus the supply of precursors for replenishing oxaloacetate is cut off) and oxaloacetate is siphoned off into gluconeogenesis