HBG 12 ( FA Synthesis )

• Fatty acid biosynthesis occurs within the cytoplasm of most animal cells
• The liver is the major site of fatty acid synthesis
• Fatty acids are synthesized when the diet is low in fat and/or high in carbohydrates and protein
• Most fatty acids are synthesized from glucose
• Fatty acid synthesis requires a large quantity of NADPH, mostly provided by the pentose phosphate pathway
• The process of fatty acid synthesis is almost the reverse of beta-oxidation, where fatty acids are constructed by the sequential addition of two-carbon groups supplied by acetyl-CoA
• Acetyl CoA carboxylase catalyzes the ATP-dependent carboxylation of acetyl CoA to malonyl CoA, which is a key regulatory site for fatty acid synthesis
• Activators of acetyl CoA carboxylase are citrate and insulin, while inhibitors are palmitoyl CoA and glucagon
• The fatty acid synthase enzyme complex catalyzes the conversion of acetyl CoA to malonyl CoA to butyryl CoA
• The formation of palmitic acid involves the reaction of butyryl-ACP with another malonyl group to form a six-carbon unit, which repeats until palmitic acid (16 carbon) is synthesized and released from ACP
• Differences between fatty acid synthesis and beta-oxidation include location, enzymes used, thioester linkage, and electron carriers
• Lipolysis occurs during fasting, vigorous exercise, and stress, where hormones release and bind to hormone receptors in adipocytes to activate a sequence of reactions
• Triacylglycerols and phosphatidylglycerols are hydrolyzed by lipases and phospholipases, respectively, with different lipases hydrolyzing different bonds on the glycerol molecule
• Elongation of fatty acids longer than 16 carbons can occur via the endoplasmic reticulum system or a mitochondrial elongation system
• Desaturation of fatty acids introduces double bonds between carbon 9 and 10 in the endoplasmic reticulum, requiring oxygen and NADPH
• Carnitine deficiency symptoms include an enlarged heart, abnormal ECG, lipid deposition in muscle biopsy, and below-normal plasma levels of carnitine
• Failure in beta-oxidation can be due to acetyl CoA carboxylase deficiency, leading to the inability to utilize biotin
• Difficulties in fatty acid biosynthesis can result from Zellweger syndrome, which is characterized by a lack of peroxisomes necessary for beta-oxidation
• Medium-chain acyl CoA dehydrogenase deficiency can cause sudden infant death syndrome due to an imbalance between glucose and fatty acid oxidation
• Refsum's disease is characterized by the inability to oxidize phytanic acid, a branched fatty acid found in dairy products, leading to nerve damage
• Obesity is a clinical correlation of fatty acid biosynthesis
• Sphingolipid storage diseases such as Tay-Sachs, Gaucher's, Krabbe's, and Niemann-Pick have associated symptoms and enzyme deficiencies