Lipids Metabolism

Author: marzia porro
Date: 05/03/2013


Ketosis is a typical state of elevate levels of ketone bodies in the body. It consists of ketonemia and keturia, therefore ketone bodies are lost both in the urine and in breath (acetone). Infact a typical symptom is the smell of acetone, similar of wasted fruit one.

The production of ketone bodies is physiological when glucose is low in blood, mostly during starvation when glycogen stores are not available. Liver is induced to synthetaize beta-hydroxybutyrate, acetoacetate and acetone from HMG-CoA, obtained by lipid catabolism. They are released to provide energy to brain because brain couldn't use fatty acids and also to muscles. Ketone bodies are then incorporated into acetyl-CoA and used in the citric acid cycle.
However child develops a state of ketoacidosis very often after an episode of fever due to an infection, starvation, stress,etc... There is evidence of the increase in ketone bodies level in adolescent ( they secrete GH at the rate of 700 microgr/day) during the last part of sleep before breakfast as GH peack in blood. And GH has hyperglycemic effect, induces lypolisis and ketogenesis. Moreover condition of stress, infection, starvation are related to high cortisol with similar metabolic effects.
Evidence for a role for insulin and growth hormone in overnight regulation of 3-hydroxybutyrate in normal and diabetic adolescent, 1993

SIGNS/SYMPTOMS: child shows halitosis, typical also of diabetic patients. Then nausea, vomiting, headache. Infact the high levels of acids in blood decrease the pH. The organism could balance with respiration this consequence at first and with renal contribution that controls the quantity of bicarbonate.
A low pH is dangerous for nervous cells because the osmotic effect makes them suffer. And it could lead the child to convulsions. Moreover ketone bodies seems to have particular effect upon synaptic activity: acetoacetate reduce quantal size at hippocampal synapses and suppresses glutamate release; and also the response of brain amino acids metabolism to ketosis consists in diminished aspartate production and potentially synthesys of glutamine and GABA.
Metabolic control of vescicular glutamate transport and release, 2010
Response of brain amino acid metabolism to ketosis, 2005
Moreover acetone has cardiac effects in animal models: norepinephrine is released under acetone (a keton body) stimulus when acetone reaches a concentration from 10 to 1000mM in blood. Above 210mM it is toxic to muscle fibers and/or pacemaker and/or the conducing system. Child shows tachycardia.
Correlation between positive chronotropic effects and norepinephrine release induced by acetone in the rat right atrium, 1987

Besides a low pH moves the dissociation curve of the hemoglobin to the right, towards the release of oxigen and a worse affinity to it. So child feels tired and fatigable.
As in the alcoholic syndrome the NAD/ NADH ratio is lowered beacuse the ketone bodies turn in acetyl-CoA.

As a consequence of the lower NAD/NADH ratio some reactions shift towards a new equilibrium: for example lactate is producted by lactate dehydrogenase from pyruvate. As in physical exercice the lactate induces wearying. Then more malate is synthetized and G3P, reducing ATP production.

REMEDIES: it's suggested to prescribe to the little patient a diet rich in carbohydrates. Infact from their digestion the glucose obtained is used to sintethyzed ATP. And glycogen stores are enriched. Moreover the insulin secreted after the meal stops ketogenesis, lypolisis, gluconeogenesis, helping the child. Instead fat food exasperate the consequences of ketosis.

CURIOSITY: very often before symptoms of ketoacidosis grandmothers support the child has a pinworm infection. There are a lot of popular belifs linked with this idea, also a bit magic. What we can notice is that some parasites increase ketonemia in the animal model. Infact they take their nourishement from the host: carbohydrates give energy, whereas amino acids and lipids are used to produce macromolecules and eggs. Maybe ketosis is confused with a case of parasitism because of his strict relation with ketoacidosis.
The serum glucose and beta-hydroxybutyrate levels in sheep with experimental Fascicola hepatica and Fascicola gigantica infection, 2007.

Some girls show ketosis during their period because sexual hormone LH changes the metabolism. Studies in animal models underline a bigger expression in genes for proteins involved in ketogenesis during and after the ovulation.
Estrus synchronization and ovarian hyper-stimulation treatements have negligible effects on cumulus oocyte complex gene expression whereas induction of ovulation causes major expression changes, 2013

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