Fatty Acid Beta-Oxidation

Fatty Acid Oxidation (Beta-Oxidation)

• Fatty acid oxidation, also known as beta-oxidation, breaks down fatty acids to generate energy.
• This metabolic pathway primarily occurs in the mitochondria of cells, especially in tissues like the liver, muscle, and adipose tissue.
• Fatty acids need activation before oxidation, a process in the cytoplasm.
• Activation involves attaching coenzyme A (CoA) to a fatty acid, forming acyl-CoA and requiring ATP.
• Acyl-CoA molecules must be transported into the mitochondria for beta-oxidation using the carnitine shuttle system.
• Within mitochondria, fatty acids undergo enzymatic reactions called beta-oxidation.
• Each beta-oxidation cycle cleaves a two-carbon unit from the fatty acid chain.
• The products of beta-oxidation include acetyl-CoA, NADH, and FADH2.
• These products enter the citric acid cycle (Krebs cycle) to generate ATP through oxidative phosphorylation.
• Acetyl-CoA from fatty acid oxidation enters the citric acid cycle for further oxidation, producing additional NADH and FADH2.
• Electron carriers donate electrons to the electron transport chain, leading to ATP production.
• Regulation of fatty acid oxidation involves hormone signals, substrate availability, and the cell's energy needs.
• Enzymes in beta-oxidation are subject to allosteric and hormonal control.
• Understanding fatty acid oxidation is essential for comprehending metabolic disorders like FAODs, resulting from defects in enzymes or transport proteins in the pathway.
• FAODs can manifest as hypoglycemia, muscle weakness, and cardiomyopathy.

Ketone Bodies

• Ketone bodies are water-soluble molecules produced by the liver from fatty acids during prolonged fasting, low carbohydrate intake, or untreated diabetes mellitus.
• The three primary ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone.
• Ketogenesis happens in the liver mitochondria.
• It involves converting acetyl-CoA (from fatty acid oxidation) into ketone bodies.
• Ketogenesis is upregulated by low insulin and high glucagon levels, indicating a need for alternative fuel sources.
• Ketone bodies are transported from the liver to extrahepatic tissues, such as muscle and brain.
• These tissues convert ketone bodies back into acetyl-CoA through ketolysis.
• Acetyl-CoA from ketone bodies can enter the citric acid cycle to produce ATP.
• Ketone body production is regulated by hormonal and metabolic factors.
• Insulin inhibits ketogenesis, while glucagon and cortisol stimulate it.
• The availability of fatty acids also affects the rate of ketone body production.
• Ketone bodies act as an alternative fuel source, especially for the brain during glucose scarcity.
• They cross the blood-brain barrier allowing neurons to oxidize them to generate ATP, preserving glucose for essential functions.
• Ketosis indicates elevated ketone bodies in the blood.
• It occurs during fasting or low-carbohydrate diets.
• Uncontrolled ketogenesis leads to ketoacidosis.
• Ketoacidosis is a life-threatening condition with high ketone levels, metabolic acidosis, and dehydration, often seen in untreated type 1 diabetes mellitus.
• Understanding ketone body metabolism is crucial for managing conditions such as diabetes mellitus
• Abnormalities in carbohydrate and lipid metabolism can lead to dysregulated ketone production and metabolic complications.

Lipid Profile and Disorders

• The lipid profile blood test measures: total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol.
• Total cholesterol represents all cholesterol in lipoproteins circulating in blood.
• Elevated total cholesterol increases the risk of atherosclerosis and cardiovascular disease.
• Triglycerides are fats in the blood, derived from dietary intake and liver synthesis.
• High triglyceride levels (hypertriglyceridemia) is linked to obesity, insulin resistance, metabolic syndrome, and cardiovascular disease risk.
• HDL cholesterol helps remove excess cholesterol from the bloodstream and transports it to the liver for excretion.
• Higher HDL cholesterol levels is associated with a reduced risk of cardiovascular disease.
• LDL cholesterol is a major carrier of cholesterol in the blood.
• Elevated LDL cholesterol contributes to atherosclerosis, increasing the risk of heart disease and stroke.
• Disorders in lipid profile is characterized by abnormalities in lipid metabolism:
• Hyperlipidemia refers to elevated lipids in the blood, including cholesterol and triglycerides, which is a risk factor for cardiovascular disease.
• Dyslipidemia is imbalances in lipid levels, such as elevated LDL, low HDL, or high triglycerides, and is associated with metabolic disorders like obesity, diabetes, and metabolic syndrome.
• Familial Hypercholesterolemia is a genetic disorder causing high LDL cholesterol from birth, leading to premature atherosclerosis and increased cardiovascular risk.
• Hypertriglyceridemia involves elevated triglyceride levels from genetic factors, dietary habits, obesity, insulin resistance, or medical conditions.
• Managing lipid profile disorders involves lifestyle modifications, pharmacotherapy (lipid-lowering medications), and addressing underlying metabolic conditions to reduce cardiovascular risk and improve overall health.