Effects of Hypoglycin A and methylenecyclopropylglycine (MCPG) First, we need to understand how the body reacts when there is not enough glucose in circulation: this can be induced by the absence of meal in poor and young children (teenagers, adults and well fed child have more stock of glycogen). So when we are in hypoglycemia (when the body doesn’t have enough glucose to degrade to produce ATP) the body need to find another source of energy and glucose so the gluconeogenesis is triggered. This metabolic pathway results in the generation of glucose from certain non-carbohydrate carbon substrates. Figure 1: the gluconeogenesis One of the main step of the gluconeogenesis is the beta-oxidation of fatty acids. Figure 3 : Beta-oxidation cycle (occur in liver cell mitochondria) The beta-oxidation is a succession of chemical reactions which occur in the mitochondria of the liver cells and which produce ATP (approximately 14 ATP per cycle) and 1 Acetyl-CoA which are essential for the Krebs cycle (and we all know the importance of the Krebs cycle). If you want to have more details about all the reaction during beta-oxidation, I suggest you to read this (short and in French) course about the lipids degradation (http://calamar.univ-ag.fr/deugsv/Documents/Cours/Bioch-Zinsou/Lipidegrad.pdf) or if you prefer to just watch someting, this video (https://www.youtube.com/watch?v=WX8sLclDyvw ). So now that we have a better understanding of the beta-oxidation, we can focus on the interaction between those toxins and the beta-oxidation cycle. Figure 4 : Conversion of MCPG and hypoglycine into active metabolites and their sites of inhibition of beta-oxidation adapted from Metabolic consequences of methylenecyclopropylglycine poisoning in rats. As shown on the Figure 4, this two toxins inhibit several enzyme necessary to the beta-oxidation cycle. MCPG mainly inhibits the 3-Oxoacyl-CoA thiolase so the beta-oxidation cycle cannot produce Acetyl-CoA anymore. Hypoglycin A target mainly Acyl-CoA dehydrogenase and stop his action, so there is an accumulation of Branched-chain-oxo-acid dehydrogenase and that can be toxic. To conclude, those two toxins block the gluconeogenesis which are essential when there is not enough glucose supply to do the glycolysis who produce ATP and glycogen in normal case. And because of the absence of evening meal and glucose stocks in these children, they cannot perform the glycolysis and due to the litchi and toxin consumption they cannot perform gluconeogenesis. The main problem of this type of hypoglycemia is that the brain have a very small stock of glucose so very quickly (in a few minutes) after the “consumption” of all the glucose stocks, the ATP levels become depleted. More than the lost of cerebral energy, the main problem of the lack of glucose is the reduced of synthesis of neurotransmitter. Indeed, glucose oxidation in the brain provide several precursors for the synthesis of some neurotransmitter (acetylcholine, glutamate,...). And when the hypoglycemia is really acute, like here,there are neuronal cell death ensues, particularly in hippocampal and cortical structure. So this is why the children arrived why seizure and falled quickly in coma or death. The discovery of the two toxin in the litchi are new and not so well described in human and there is still some part a little bit vague. For example, there is a possibility that this toxin also impact carnitine which allow the way between mitochondria and cytosol for fatty acid, acetyl-CoA and other molecules. Also, there is a high possibility that this disease have some genetic factor, because some children didn’t become ill even if they have eat litchi only all day. So there is still a lot of things to discover around this two toxins. What you should bring home ? Litchi contain two toxin which disturb and block some part of ATP and glucose production. In “normal” case (adults, well feed, few litchi eaten), the other system of energy product will not be disturbed because we have enough glucose stock to avoid the hypoglycemia. But for Indian child who eat only litchi in an entire day, without a correct meal and without glycogen reserve, those toxin become dangerous and mortal. To avoid this, Indian Government has written some basics recommendation: don’t let the child eat litchi in orchard all day and give them a strong diner before let them all night without glucose intake. Figure 5 : Schema to summarize all our case
3 Comments
Margaux
20/4/2017 04:39:56 am
litchis are evil. It's been 22 years that I try to unveil this truth to people around me but now I have proof!
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margaux
20/4/2017 04:42:58 am
oops, second question about a threshold
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Amélie
25/4/2017 03:28:34 am
Hello Margaux,
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