Oxidation of unsaturated fatty acids
About half of fatty acids in a human body are unsaturated. β-Oxidation of these acids follows the normal pathway until the double bond will not appear between the third and fourth atoms of carbon. Then the enzyme enoyl-CoA isomerase moves the double bond from position 3-4 to position 2-3 and variates cis-conformation of the dual link to trans-, which is required for β-oxidation. In this cycle of β-oxidations the first reaction of dehydrogenation does not occur, because the double bond in the fatty acid radical is already available. Further cycles of β-oxidations proceed as usual.
Violations of fatty acids oxidation
People with hereditary defects of carnitine acyl transferase I or enzymes of carnitine synthesis in skeletal muscles have decreased velocity of receipt of fatty acids in mitochondrion matrix and, accordingly, β- oxidations rate. In these cases fatty acids with the long chain are not used as energy sources. Such people's ability to physical activity is reduced; fats can accumulate and form vacuoles in cells.
There is a genetical defect of medium chain acyl CoA dehydrogenase. Brest milk fats serve as the basic energy source for babies. Fatty acids with average chain length prevail in milk fats. Impossibility to use fatty acids as energy sources leads to increase of glucose oxidation rate. As a result children get hypoglycemia. It is the cause of sudden infant death syndrome – an unexpected overnight death of infants (10% of the total number of died newborns). If such children survive, after 6-8 hours of starvation they get hypoglycemic attacks (weakness, dizziness, vomiting, and consciousness loss).
In all cases when β-oxidation is broken, fatty acids accumulate in cells and break up as they go through ω-oxidations. As a result the dicarboxylic acids are formed which are excreted with urine. Appearance of these acids in urine can serve as a diagnostic mark of the infringement of β-oxidation.
Acetyl-CoA metabolism
Acetyl-CoA is the universal donor of acetyl groups for acetylation reactions, and also takes part in tricarboxylic acids cycle with the help of glyoxylate cycle. This process is important for the synthesis of carbohydrates.
Inclusion of acetyl-CoA in tricarboxylic acid cycle (Krebs cycle) depends on the availability of oxaloacetate. When starving or having diabetes oxaloacetate is spent for the glucose formation. Under such conditions ketone bodies are formed from acetyl-CoA.
Ketone bodies are acetoacetate СН3СОСН2СООН, β-hydroxybutyrate СН3СНОНСН2СООН and acetone СН3СОСН3. Ketone bodies are formed in liver. In healthy person's blood ketone bodies are present in very small concentration, in the case of pathologies their amount increases.
Liver serves as the basic place of acetoacetate and 3-hydrooxibutyrate formation. The heart muscle and the kidney cortex preferably use acetoacetate as their "fuel" instead of glucose. Contrary to it, glucose is the main "fuel" for brain of people receiving balanced nutrition. When starving and having diabetes the brain adapts for acetoacetate use.
In peripheric tissues 3-hydrooxibutyrate is capable of being oxidized to acetoacetate, and further to acetyl-CoA.
In blood of a healthy person ketone bodies are very few (in blood serum it is 0,03-0,2 mmol/l). In pathological conditions (persons with the heavy form of diabetes, starvation) concentration of ketone bodies in blood can reach 16-20 mmol/l. Ketonemia is usually accompanied by ketonuria.