Carnitine Shuttle Process Quiz

Fatty Acid Oxidation

• Carnitine shuttle: transports fatty acyl CoA into the mitochondrial matrix, where fatty acid oxidation takes place.
• Fatty acyl CoA is converted to fatty acyl carnitine by carnitine palmitoyltransferase I, which is inhibited by malonyl-CoA.
• Short- and medium-chain fatty acids (less than 12 carbons) enter the mitochondria without the aid of carnitine or CPT system.

β-Oxidation

• Sequence of 4 reactions that result in shortening by two carbons.
• Oxidation of a molecule of palmitoyl CoA to CO2 and H2O produces 8 acetyl CoA, 7 NADH, and 7 FADH2.
• Activation of fatty acid requires 2 ATP, but produces only 2 ATP.
• Oxidation of fatty acids with an odd number of carbons requires biotin.

Ketone Body Synthesis

• Takes place in liver mitochondria from acetyl CoA.
• Ketone bodies are: acetoacetate, β-hydroxybutyrate, and acetone (a non-metabolized side product).
• Acetoacetate and β-hydroxybutyrate are transported in blood to peripheral tissues, where they can be reconverted to acetyl CoA and oxidized by TCA.

Characteristics of Ketone Bodies

• Soluble in aqueous solution.
• Produced in liver during periods when the amount of acetyl CoA present exceeds the oxidative capacity of liver.
• Used by extrahepatic tissues.

Regulation of Cholesterol Synthesis

• HMG CoA reductase is the rate-limiting enzyme in cholesterol synthesis.
• When sterol levels are low, increased synthesis of HMG CoA reductase occurs.
• Insulin favors up-regulation of HMG CoA reductase gene expression, while glucagon has the opposite effect.
• Statins (e.g., atorvastatin, fluvastatin) are competitive inhibitors of HMG CoA reductase used in cholesterol therapy.

Degradation of Cholesterol

• Ring structure cannot be metabolized.
• Sterol nucleus is eliminated by conversion to bile acids and bile salts.
• Bile acids are amphipathic, acting as emulsifying agents in the intestines, helping pancreatic digestive enzymes.

Bile Acid Synthesis

• Takes place in the liver by a multistep, multiorganelle pathway.
• Bile acids are synthesized from cholesterol, and their structure is important for their function.

Medium-Chain Fatty Acyl CoA Dehydrogenase (MCAD) Deficiency

• Autosomal recessive disorder, the most common inborn error of FA oxidation.
• Causes decrease in FA oxidation and severe hypoglycemia.
• Infants are particularly affected, as milk contains primarily medium-chain fatty acids.
• MCAD deficiency can cause sudden infant death syndrome and Reye syndrome.