HBG 11 ( OX of Fatty Acid and Ketogenesis)

• Beta-oxidation of saturated, monounsaturated and polyunsaturated fatty acids is a process in fatty acid oxidation.
• Energy yield of fatty acid oxidation is a topic in fatty acid oxidation.
• Alpha-oxidation is a process in fatty acid oxidation.
• Oxidation of branched chain fatty acids (eg phytanic acid) and Refsum disease is a topic in fatty acid oxidation.
• Control and regulation of fatty acid oxidation is a topic in fatty acid oxidation.
• Excessive oxidation of fatty acid and ketogenesis occur during starvation and diabetic mellitus.
• Ketogenesis in the liver and extrahepatic tissues is a topic in fatty acid oxidation.
• Utilization of ketone bodies by the extrahepatic tissues is a topic in fatty acid oxidation.
• Carnitinepalmitoyltransferase deficiency and Acyl-CoA dehydrogenase deficiency are clinical correlations in fatty acid oxidation.
• Ketogenesis is a metabolic pathway that produces ketone bodies, which are a group of molecules containing ketone.
• Ketone bodies provide an alternative form of energy during the neonatal period, starvation or prolonged physical efforts and are regulated by insulin.
• Beta-oxidation is a four-step process, which repeats until the fatty acid has been completely broken down.
• Beta oxidation breaks down fatty acids to produce energy.
• The four steps of beta-oxidation are dehydrogenation, hydration, oxidation, and thiolysis.
• In the first step of beta-oxidation, an acyl-CoA-ester is dehydrogenated to yield a trans-2-enoyl-CoA.
• Zellweger syndrome is characterized by the lack of peroxisomes.
• Most of the acetyl-CoA produced from the FA oxidation is used by the citric acid cycle or in isoprenoid synthesis.
• Deficient of medium-chain acyl CoA dehydrogenase (MCAD) can cause sudden infant death syndrome (SIDS) due to an imbalance between glucose and FA oxidation.
• Specifically, fatty acyl-CoA chains are broken down into acetyl-CoA, FADH2, NADH, water and one acyl-CoA chain that is two carbons shorter.
• Medium chain acyl-CoA will further degraded via b-oxidation in mitochondria.
• The second step of beta-oxidation involves hydration of the double bond, oxidation of hydroxylated beta-carbon, and finalization by the thiolytic cleavage of beta-ketoacyl CoA.
• Failure in b-oxidation is associated with Acetyl CoA carboxylase deficiency, which is an inability to utilize biotin.
• In the inner mitochondrial membrane, CPT2 then converts the long-chain acylcarnitine back to long-chain acyl-CoA.
• Acetyl CoA and Malonyl CoA are involved in difficulties in fatty acid biosynthesis.
• Beta-oxidation is a cyclic process in which fatty acyl-CoAs are shortened, whereby the two carboxy-terminal carbon atoms are released as acetyl-CoA units each time a cycle is fully completed.
• The accumulation of phytanic acid causes nerve damage due to lack of a-hydroxylating activity.
• Refsum’s disease (phytanic acid storage syndrome) is characterized by the inability to oxidize phytanic acid.
• Mitochondria cannot activate long chain FA, therefore peroxisomal carnitine acyltransferase catalyzes the transfer into peroxisome.
• Long chain FA are synthesized by the action of Acetyl CoA and Medium chain acyl-CoA.
• b-oxidation in peroxisomes is used to shorten very long chain FA such as C24:0 or C26:0.
• a-oxidation is a mechanism for oxidation of branched FA such as phytanic acid, which is a branched C20 FA found in dairy products.
• Under normal conditions, only small amount of excess acetyl-CoA produced from fatty acid oxidation occurs.
• Some conditions such as starvation, diabetes and some metabolic disorders, ketogenesis occur (usually breakdown of lipid in the absence of CHO).
• Production of ketone bodies from acetyl-CoA is a process in ketogenesis.
• Provision of peripheral tissues, such as Skeletal muscle and heart with ketone bodies spares organs depending on glucose as energy source.
• The yield of ATP from the oxidation of palmitoyl-CoA will generate 7 FADH2 x 2 ATP/FADH2 = 14 ATP, 7 NADH2 x 3 ATP/NADH2 = 21 ATP, and 8 Acetyl-CoA x 1 2 ATP/Acetyl-CoA = 96 ATP.
• Palmitoyl acid has 16 carbons, so it can be broken down into -8 acetyl-CoA molecules, -7 β-oxidation steps.
• Oxidation of NADH2 yields approximately 3 molecules of ATP.
• Symptoms in diabetes include Hyperglycemia (high blood glucose levels), Glucosuria (kidney’s capacity to reabsorb glucose from the urinary filtrate is limited, glucose appears in the urine), and Glucosuria results in osmotic diuresis, a process in which an excessive loss of water and electrolytes (Na+, K+, and Cl - ) is caused by the presence of solute in the filtrate.
• Oxidation of each FADH2 during ETC and oxidative phosphorylation yield approximately 2 molecules of ATP.