6 Fatty acid synthesis occurs in cellular compartments having a high NADPH/NADP+ ratio O NAD and nadp have selected for functioning as electron carriers in oxidative catablism and reductive anabolism respectively o In the hepatocytes and adipocytes, NADPh is mainly produced in the cytosol via the pentose phosphate pathway and by the malic enzyme In photosynthetic plants, fatty acid synthesis occur in the chloroplast stroma, using NADPH made from photophosphorylation
6. Fatty acid synthesis occurs in cellular compartments having a high NADPH/NADP+ ratio ⚫ NAD and NADP have selected for functioning as electron carriers in oxidative catablism and reductive anabolism respectively. ⚫ In the hepatocytes and adipocytes, NADPH is mainly produced in the cytosol via the pentose phosphate pathway and by the malic enzyme. ⚫ In photosynthetic plants, fatty acid synthesis occur in the chloroplast stroma, using NADPH made from photophosphorylation
COO NADP(NADPH+H CO0 CHOH CHa CH3 NADP NADPH NADP(NADPH coo Ma Glucose Malate Ribulose enzyrre pyruvate 6-phosphate 5-phosphate Pentose phosphate pathway NADPH in the cytosol of animal cells is largely produced by the oxidative decarboxylation of malate and the pentose phosphate pathway
Malic enzyme Pentose phosphate pathway NADPH in the cytosol of animal cells is largely produced by the oxidative decarboxylation of malate and the pentose phosphate pathway
7. The acetyl groups of the mitochondrion are transported into the cytosol in the form of citrate o The acetyl-Coa molecules are made from glucose and amino acids in mitochondria o The are shuttled into the cytosol in the form of citrate via the citrate transporter of the inner membrane o Acetyl-CoA is regenerated by the action of ATP-dependent citrate lyase in the cytosol. o Oxaloacetate is shuttled back into the mitochondria as malate or pyruvate
7. The acetyl groups of the mitochondrion are transported into the cytosol in the form of citrate ⚫ The acetyl-CoA molecules are made from glucose and amino acids in mitochondria. ⚫ The are shuttled into the cytosol in the form of citrate via the citrate transporter of the inner membrane. ⚫ Acetyl-CoA is regenerated by the action of ATP-dependent citrate lyase in the cytosol. ⚫ Oxaloacetate is shuttled back into the mitochondria as malate or pyruvate
Inner Outer men membrane Matrix Citrate transporter Glucose Citrate CoA-SH Fatty acid Pyruvate hes ADP+ Pi pyruvate AcetvI-CoA citrate dehydrogenase Acetyl-CoA Amino NADH+H+ malate dehyde NADH NAD +H dihydro ADP P NAD NADPT pyruvate carboxylase malic Malate- NADPH+H CO2 ketoglutarate 02 Pyruvate Pyruvate transporter
8. The rate of fatty acid biosynthesis is controlled by acetyl-CoA carboxylase o Excess fuel is generally converted to fatty acids/triacylglycerol for longer term storage o Acetyl-CoA carboxylase, catalyzing the committing and rate-limiting step of fatty acid synthesis, is allosterically inhibited by palmitoyl Coa and activated by citrate o Glucagon and epinephrine triggers the phosphorylation and disassociation of the polymeric enzyme subunits, which inactivates the enzyme
8. The rate of fatty acid biosynthesis is controlled by acetyl-CoA carboxylase ⚫ Excess fuel is generally converted to fatty acids/triacylglycerol for longer term storage. ⚫ Acetyl-CoA carboxylase, catalyzing the committing and rate-limiting step of fatty acid synthesis, is allosterically inhibited by palmitoylCoA and activated by citrate. ⚫ Glucagon and epinephrine triggers the phosphorylation and disassociation of the polymeric enzyme subunits, which inactivates the enzyme