Biochem Ketone Bodies (Chp 27)

For unsaturated and odd-number double bond fatty acids, oxidation requires:

cis-Δ³-enoyl CoA isomerase to convert cis-Δ³-enoyl CoA that was produced at the end of β-oxidation into trans-Δ²-enoyl CoA

For unsaturated and even-number double bond fatty acids, oxidation requires:

2,4-dienoyl CoA reductase to convert 2,4-dienoyl CoA and cis-Δ³-enoyl CoA isomerase converts cis-Δ³-enoyl CoA into trans-Δ²-enoyl CoA

β oxidation of odd-numbered total carbon fatty acids generates:

propionyl CoA in the last thiolysis reaction

propionyl CoA carboxylase

adds a carbon to propionyl CoA to form methylmalonyl CoA

methylmalonyl CoA mutase

forms succinyl CoA from methylmalonyl CoA by converted between D and L formation; requires vitamin B12

ketone-body synthesis

takes place in liver mitochondria, produces ketone bodies such as acetoacetate, β-hydroxybutyrate, and acetone from acetyl CoA and releases them into the blood as fuel

Name the enzymes of ketone body synthesis:

1.) 3-ketothiolase

2.) hydroxymethylglutaryl CoA synthase

3.) hydroxymethylglutaryl CoA cleavage enzyme

4.) d-3-hydroxybutyrate dehydrogenase

D-3-hydroxybutyrate is formed upon:

the reduction of acetoacetate

Acetone is generated by:

spontaneous decarboxylation of acetoacetate

Clinical Insight: How are ketogenic diets utilized?

ketogenic diets are rich in fats, low in carbs, adequate in proteins and lead to substantial amounts of ketone bodies; frequently used to reduce seizures in children suffering from drug-resistant epilepsy

True or False: Animals can convert fatty acids into glucose

False; because 2 carbons are lost as CO₂ before oxaloacetate is regenerated, synthesis of oxaloacetate and glucose can’t happen

Clinical Insight: Explain diabetic ketosis

excess production of ketone bodies can lead to acidosis, which often occurs when diabetes is left untreated

Clinical Insight: How are ketone bodies important during starvation?

during starvation, protein degradation is the initial source of carbons; after several days of fasting, the brain begins to use ketone bodies which curtail protein degradation and prevents tissue failure until TAG is depleted

Clinical Insight: What fatty acids contribute to pathological conditions?

Overconsumption of saturated and trans unsaturated fatty acids promotes obesity, atherosclerosis and type 2 diabetes