QUESTION OF THE DAY
A 35-year-old man in New York City, originally from Jamaica, purchased an illegally imported fruit from a street vendor and, within 4 hours of eating the fruit, began vomiting severely. When brought to the emergency department the man was severely dehydrated and exhibited several seizures. The toxic effects of the fruit were interfering with which of the following?
A. Fatty acid release from the adipocytes
B. Fatty acid entry into the liver cell
C. Fatty acid activation
D.Fatty acid oxidation
E. Oxidative phosphorylation
Answer- D- Fatty acid oxidation.
The patient is suffering from Jamaican vomiting sickness.
Jamaican vomiting sickness is caused by eating the unripe fruit of the ackee tree, which contains the toxin hypoglycin that inactivates medium and short-chain acyl-CoA dehydrogenase, inhibiting β -oxidation and causing hypoglycemia.
Acyl co A dehydrogenase catalyzes the first step of Beta oxidation of fatty acids as they are transported inside the mitochondria (figure-1 and 2).
Figure-1- Reaction catalyzed by acyl co A dehydrogenase
The acyl co A dehydrogenases are specific for the chain length of fatty acids. There are three types of Acyl co A dehydrogenases depending upon the chain length of the fatty acids- short (C4-C6), medium (C6-C12) and long chain (C12) acyl co A dehydrogenases. The block at the level of medium chain acyl co A dehydrogenase impairs the fatty acid oxidation (figure-2).
Figure-2- Steps of beta oxidation, Acyl co A dehydrogenase catalyzes the first step of beta oxidation .
Typical symptoms include vomiting, lethargy and coma accompanied by hypoketotic hypoglycemia.
With a medium- and short-chain acyl-CoA dehydrogenase, deficiency, gluconeogenesis is impaired due to a lack of energy from fatty acid oxidation, and an inability to fully activate pyruvate carboxylase, as acetyl-CoA activates pyruvate carboxylase, and acetyl-CoA production from fatty acid oxidation is greatly reduced.
In an attempt to generate more energy, medium-chain fatty acids are oxidized at the ω ends to generate the dicarboxylic acids. Excessive production of dicarboxylic acids leads to dicarboxylic aciduria.
The absence of ketosis is accounted for by the block in fatty acid oxidation.
The acyl co A dehydrogenase deficiencies represent a recently discovered group of inherited defects. The affected enzymes may be short, medium or long chain acyl co A dehydrogenases. The best characterized is medium chain acyl co A dehydrogenase deficiency. In retrospect, it now seems likely that many cases previously diagnosed as “Reye –like-syndrome” or “sudden infant death syndrome” were in fact due to Medium chain acyl co A dehydrogenase deficiency.
Fatty acid release from adipocytes, fatty acid entry in to liver cells, fatty acid activation or oxidative phosphorylation, none of these processes are affected in Jamaican sickness.