Chapter 25: Lipids: Lipolysis, Fatty Acid Oxidation, and Ketogenesis
Parents of a 3-month-old infant arrive at the ER agitated and frightened by the extreme lethargy and near comatose state of their child. Examination shows the infant to be severely hypoglycemic accompanied by low measurable ketones in the urine and blood. Blood analysis also indicates an elevation in butyric and propionic acids and as well as C8-acylcarnitines. A deficiency in which of the following enzymes is most likely responsible for these observations?
B. hormone-sensitive lipase (HSL)
C. lipoprotein lipase (LPL)
D. long-chain acyl-CoA dehydrogenase (LCAD)
E. medium-chain acyl-CoA dehydrogenase (MCAD)
Answer E: In infants, the supply of glycogen lasts less than 6 hours and gluconeogenesis is not sufficient to maintain adequate blood glucose levels. Normally, during periods of fasting (in particular during the night) the oxidation of fatty acids provides the necessary ATP to fuel hepatic gluconeogenesis as well as ketone bodies for nonhepatic tissue energy production. In patients with MCAD deficiency there is a drastically reduced capacity to oxidize fatty acids. This leads to an increase in glucose usage with concomitant hypoglycemia. The deficit in the energy production from fatty acid oxidation, necessary for the liver to use other carbon sources, such as glycerol and amino acids, for gluconeogenesis further exacerbates the hypoglycemia. Normally, hypoglycemia is accompanied by an increase in ketone formation from the increased oxidation of fatty acids. In MCAD deficiency there is a reduced level of fatty acid oxidation, hence near-normal levels of ketones are detected in the serum.
Oxidation of fatty acids requires the input of energy in the form of ATP. Which of the following enzyme activities requires this energy input?
A. acyl-CoA dehydrogenases
Answer B: Fatty acids must be activated in the cytoplasm before being oxidized in the mitochondria. Activation is catalyzed by fatty acyl-CoA synthetases (also called acyl-CoA ligases or thiokinases). The net result of this activation process is the consumption of 2 molar equivalents of ATP.
Very-long-chain fatty acids (VLCFA) are oxidized in the peroxisomes. The process of oxidation of these fats is referred to as which of the following?