fatty acid oxidation and ketones

Question 1

sources of energy in the body

Answer 1

carbohydrates (can sustain for 12 hours)

fats (can sustain for 12 weeks), protein (used when muscle glycogen stores fail)

Question 2

fatty acid

Answer 2

carboxylic head with aliphatic tail, saturated or unsaturated, most are derived from triglycerides and phosphate

Question 3

fatty acid activation

Answer 3

fatty acids must be activated in the cytoplasm before they can be oxidised in the mitochondria
if the acyl-CoA < 12 carbons - can diffuse through mitochondrial membrane
most dietary fatty acids have > 14 carbons - taken through mitochondrial membrane using carnitine shuttle

Question 4

utilisation of Acetyl-CoA

Answer 4

under normal metabolic conditions most Acetyl-CoA is utilised via the TCA acid cycle to produce glucose
A small proportion of Acetyl-CoA is converted into ketones
during high rates of fatty acid oxidation, large amounts of acetyl-CoA are generated
this exceeds the capacity of the TCA cycle which results in ketogenesis

Question 5

ketones

Answer 5

molecules produced by the liver from acetyl-CoA

have characteristic fruity/ nail polish remover smell

Question 6

Ketogenesis

Answer 6

Acetoacetate can undergo spontaneous decarboxylation to acetone, or be enzymatically converted to beta-hydroxybutyrate
ketone bodies utilised by extrahepatic tissues through conversion of beta-hydroxybutyrate and acetoacetate to acetoacetyl-CoA
this requires the enzyme acetoacetate: succinyl-CoA transferase, which is found in hepatic tissue

Question 7

regulation of ketogenesis

Answer 7

affected by several factors:

release of free fatty acids from adipose tissue
high conc of glycerol-3-phosphate in the liver results in triglyceride production, whilst a low level results in increased ketone body production
when demand for ATP is high, acetyl-CoA is likely to be further oxidised via the TCA cycle to carbon dioxide
fat oxidation is dependant upon the amount of glucagon (activation) or insulin (inhibition) present

Question 8

clinical significance of ketogenesis

Answer 8

carbohydrate shortages cause the liver to increase ketone body production from acetyl-CoA
the heart and skeletal muscles preferentially utilise ketone bodies for energy preserving in the brain

Question 9

ketoacidosis

Answer 9

occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement
is often the presenting feature in newly diagnosed type 1 diabetics
also occurs in chronic alcohol abuse
patients present with hyperventilation and vomiting

Question 10

consequences of ketoacidosis

Answer 10

ketones are relatively strong acids
excessive ketones lower the pH of the blood
the impairs the ability of haemoglobin to bind to oxygen