1. 24.4 Ketogenesis and Ketone Bodies
The accumulation of ketone bodies may lead to a condition called ketosis, which occurs in cases of severe diabetes, diets high in fat and low in carbohydrates, alcoholism, and starvation. A ketone test strip indicates the level of ketone bodies in a urine sample.
Learning Goal Describe the pathway of ketogenesis.

2. Ketogenesis and Ketone Bodies
If carbohydrates are not available,
fatty acids break down to meet energy needs.
acetyl CoA molecules combine to form ketone bodies.
When large quantities of fatty acids are degraded,
too much acetyl CoA is produced.
high levels of acetyl CoA accumulate in the liver.
acetyl CoA molecules combine in a pathway known as ketogenesis to form compounds called ketone bodies.
Core Chemistry Skill Describing How Ketone Bodies Are Formed

3. Reaction 1: Condensation
In ketogenesis,
two molecules of acetyl CoA combine to form acetoacetyl CoA and HS — CoA.
this condensation is in the opposite direction of the last step of β oxidation.

4. Reaction 2: Hydrolysis The hydrolysis of acetoacetyl CoA
forms acetoacetate, a ketone body, and HS — CoA.
Acetoacetate can enter the citric acid cycle by reforming acetyl CoA for energy production or break down into other ketone bodies.

5. Reaction 3: Hydrogenation
Acetoacetate is reduced by 2H from NADH + H+ to β-hydroxybutyrate, which is considered a ketone body even though it does not contain a keto group.

6. Reaction 4: Decarboxylation
Acetoacetate can also undergo decarboxylation to yield acetone, a ketone body, and CO2.

7. Ketosis Ketosis occurs
in cases of diabetes, diets high in fat, and starvation.
as ketone bodies accumulate.
when acidic ketone bodies lower blood pH below 7.4 (acidosis).

8. Chemistry Link to Health: Ketone Bodies and Diabetes
In diabetes,
insulin does not function properly.
glucose levels are insufficient for energy needs.
fats are broken down to acetyl-CoA.
ketogenesis produces ketone bodies.

9. Chemistry Link to Health: Ketone Bodies and Diabetes
Type 1, insulin-dependent diabetes, which often begins in childhood,
is characterized by the pancreas’s producing inadequate levels of insulin.
can result from pancreatic damage by viral infections or from genetic mutations.
In type 2, insulin-resistant diabetes, characteristic of adults,
insulin is produced, but insulin receptors are not responsive.
a person will not respond to insulin therapy.
Gestational diabetes can occur during pregnancy, but blood glucose levels usually return to normal after the baby is born.

10. Chemistry Link to Health: Ketone Bodies and Diabetes
In all types of diabetes,
insufficient amounts of glucose are available in the muscle, liver, and adipose tissue.
liver cells synthesize glucose from noncarbohydrate sources via gluconeogenesis, which elevates levels of acetyl CoA.
excess acetyl CoA undergoes ketogenesis, and ketone bodies accumulate in the blood.
a person with uncontrolled diabetes can go into ketosis.

11. Study Check
In ketogenesis, match the type of reaction with the appropriate description. A. Acetoacetate produces acetone. 1) oxidation 2) reduction 3) decarboxylation B. Acetoacetate produces β-hydroxybutyrate. 1) oxidation 2) reduction 3) decarboxylation

12. Solution
In ketogenesis, match the type of reaction with the appropriate description. A. Acetoacetate produces acetone. 3) decarboxylation B. Acetoacetate produces β-hydroxybutyrate. 2) reduction