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← Theoretical B

Q5 — Ketogenic Diet Metabolism and Catecholamine Seizure Latency

Theoretical B Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license
Bioenergetics & Central Metabolism Overview

Ketogenic (high-fat, low-carbohydrate) diet is an efficient treatment for recurrent seizures, as in epilepsy. Ketogenic diet is thought to exert its effect via a metabolic pathway shown in Figure 1, as it leads to a production of beta-hydroxybutyrate. Increasing the number of reactions in a biochemical pathway decreases its overall reaction rate.

A metabolic pathway diagram connecting glycolysis, ketolysis, the TCA cycle, and the glutamate/GABA shunt, with three numbered reaction steps circled. Figure 1. Glycolysis and ketolysis both feed into the TCA cycle via acetyl-CoA (reaction 1) and citrate (reaction 2); TCA-cycle intermediates alpha-ketoglutarate and oxaloacetate connect to the glutamate/GABA/aspartate shunt (reaction 3).

Dopamine is known to play a role in muscle control (e.g., its deficiency is one of the causes of Parkinson’s disease). A study investigated the interaction of catecholamines (dopamine, noradrenaline, and adrenaline) with a ketogenic diet. The study used Dbh knockout (Dbh-/-) and heterozygote (Dbh+/-) mice that were fed with either a ketogenic or normal diet. To estimate the efficacy of the diet in each group, they were introduced to fluorothyl (a seizure-inducing agent), and the latency to the first seizure was measured.

Left: a pathway from tyrosine through L-DOPA, dopamine, noradrenaline (via DBH), and adrenaline (via PNMT). Right: a bar chart of seizure latency threshold for Dbh+/- and Dbh-/- mice on normal vs. ketogenic diet, with the ketogenic diet only raising the threshold significantly in Dbh+/- mice. Figure 2. A Metabolism of catecholamines. B Seizure latency threshold (in milliseconds) after provocation with fluorothyl in Dbh +/- and -/- mice fed either the standard or ketogenic diet. Asterisk indicates a significant difference.

On your answer sheet, indicate “T” for true statements and “F” for false ones.

A. A ketogenic diet facilitates the conversion of alpha-ketoglutarate to glutamate.
B. A mutation reducing the Km of the enzyme that catalyzes reaction 2 in Figure 1 decreases the value of the seizure latency (in milliseconds) in (Dbh+/-) mice with a ketogenic diet.
C. L-DOPA can be used as both an anti-convulsant and a treatment for Parkinson's disease.
D. The study is certainly conclusive that noradrenaline enhances GABA's anti-seizure functions.
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Question reproduced from IBO 2024, Theoretical Exam Part B, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF