Question

(BioChem) Acyl-CoA dehydrogenase deficiencies are diseases related to the impaired ability to oxidize fatty acids via beta oxidation. Symptoms of these acyl-CoA dehydrogenase deficiencies include hypoketosis [low blood levels of ketone bodies], hypoglycemia [low blood glucose], and hyperammonemia [increased blood levels of ammonia] during long periods of fasting. (Please type response, thanks!)

a.) In what 2 ways is beta oxidation important during prolonged periods of fasting?

b.) Please explain why patients with acyl-coA dehydrogenase deficiencies have bouts of hypoketosis [1- 2 sentences is sufficient].

c.) Please explain why patients with acyl-coA dehydrogenase deficiencies have bouts of hypogycemia [1- 2 sentences is sufficient].

d.) Please explain why patients with acyl-coA dehydrogenase deficiencies have bouts of hyperammonemia [1- 2 sentences is sufficient].

Answer 1

a) In what 2 ways is β-oxidation important during prolonged periods of fasting?

Under short starvation, body’s glycogen is depleted to form glucose which is the major energy fuel. However, under prolonged periods of fasting, body fats (storage fuel for long-term use) are mobilized to supply energy requirement for the body function.

i. These fatty acids are metabolized via β-oxidation to produced acetyl-CoA which generates energy (ATP) via TCA cycle, ETC, and oxidative phosphorylation.

ii. As β-oxidation of fatty acids fulfil the energy demand under prolonged fasting, glucose (which is already in low concentration) need not to be metabolized for energy production. So, this helps maintaining blood glucose levels.

iii. Under prolonged fasting conditions, blood glucose levels often drop as most of the glucose is being degraded for energy supply. Cells try to keep the blood glucose levels normal by generating glucose via gluconeogenesis. Few of TCA cycle intermediates like oxaloacetate enters gluconeogenesis. In this way, β-oxidation supplies substrates via acetyl-CoA/TCA cycle/oxaloacetate to gluconeogenesis

b) Why patients with acyl-coA dehydrogenase deficiency have hypoketosis?

Lack of acyl-CoA dehydrogenase leads to inability to oxidize fatty acids thereby cells cannot produce acetyl-CoA which is the precursor for ketone bodies. Lack of acetyl-CoA leads to reduced levels of ketone bodies in the body (hypoketosis).

c) Why patients with acyl-CoA dehydrogenase deficiency have hypoglycaemia?

Lack of acyl-CoA dehydrogenase leads to inability to oxidize fatty acids thereby cells have to depend on other sources of fuels like carbohydrates and amino acids to produce energy to survive. This dependence of cells on carbohydrates for energy reduces blood glucose level (hypogylcemia) because most of the blood glucose is being utilized by cells to generate energy.

d) Why patients with acyl-CoA dehydrogenase deficiency have hyperammonemia?

Lack of acyl-CoA dehydrogenase leads to inability to oxidize fatty acids thereby cells have to depend on other sources of fuels like carbohydrates and amino acids to produce energy to survive. This dependence of cells on amino acids for energy increases blood ammonia level (hyperammonemia) because amino acids are constantly being degraded to generate energy. Constant degradation of amino acids generates more ammonia and urea.