82 - Fatty Acid Metabolism

Definition of beta oxidation

Beta oxidation is the **catabolic breakdown of fatty acids** that produces **acetyl-CoA, NADH, and FADH₂**

Why beta oxidation is called an oxidative process

Each round produces **reducing equivalents (NADH and FADH₂)** by removing electrons from fatty acids

Number of reactions in one round of beta oxidation

Each round consists of **four reactions**

Products generated in one round of beta oxidation

**1 NADH, 1 FADH₂, and 1 acetyl-CoA (after cleavage)**

What happens to the fatty acyl chain during beta oxidation

The fatty acyl chain is **shortened by two carbons** in each round

Why beta oxidation repeats in cycles

The shortened acyl-CoA **re-enters the pathway** until fully broken down

Final products of beta oxidation of even-numbered fatty acids

Entire fatty acid is broken into **two-carbon acetyl-CoA units**

Example of beta oxidation using palmitate (16 carbons)

Palmitate undergoes **7 rounds of beta oxidation** to produce **8 acetyl-CoA, 7 NADH, and 7 FADH₂**

Fate of acetyl-CoA produced from beta oxidation

Acetyl-CoA enters the **citric acid cycle** for further oxidation

Fate of NADH and FADH₂ from beta oxidation

They donate electrons to the **electron transport chain** to generate ATP

Alternative fate of acetyl-CoA during starvation

Acetyl-CoA is converted into **ketone bodies**

Definition of ketogenesis

The production of **ketone bodies from acetyl-CoA** in the liver

Conditions that trigger ketone body production

**Fasting or starvation**, when glucose levels are low

Reason ketone bodies are produced during starvation

To provide an **alternative energy source for the brain**

Why fatty acids cannot directly fuel the brain

Fatty acids **cannot cross the blood-brain barrier**

Major ketone bodies produced in humans

**Acetone, acetoacetate, and beta-hydroxybutyrate**

How ketone bodies support brain metabolism

Ketone bodies cross the **blood-brain barrier** and are converted to **acetyl-CoA**

Why ketone bodies are considered an emergency fuel

They are used when **glucose stores are depleted**

Definition of fatty acid biosynthesis

Fatty acid biosynthesis is the **anabolic synthesis of fatty acids from acetyl-CoA**

Major difference between beta oxidation and fatty acid synthesis

They use **different enzymes** and occur in **different cellular locations**

Conceptual relationship between beta oxidation and fatty acid synthesis

Fatty acid synthesis is conceptually **the reverse of beta oxidation**

What building block is added during fatty acid synthesis

**Two-carbon units from acetyl-CoA** are added to a growing fatty acid chain

When fatty acid synthesis occurs

During **excess carbohydrate intake**, when glucose is abundant

Source of acetyl-CoA used in fatty acid synthesis

Derived from **glucose metabolism via glycolysis and PDH**

Why acetyl-CoA is diverted to fat synthesis when energy is abundant

Excess acetyl-CoA is **stored as fatty acids** rather than oxidized

What type of reaction fatty acid synthesis represents

An **anabolic and reductive** process

Primary reducing equivalent used in fatty acid synthesis

**NADPH**

Why NADPH is required in fatty acid synthesis

NADPH donates **electrons to reduce carbon chains** during synthesis

Key difference between NADPH and NADH roles

**NADPH** supports biosynthesis, while **NADH** supports ATP production

Why acetyl-CoA must be transported out of mitochondria for fat synthesis

Fatty acid synthesis occurs in the **cytosol**, not the mitochondria

Transport form used to move acetyl-CoA to cytosol

Acetyl-CoA is transported as **citrate**

Name of enzyme responsible for fatty acid synthesis

**Fatty acid synthase**

Major product synthesized by fatty acid synthase

The **16-carbon fatty acid palmitate**

Number of acetyl-CoA molecules required to make palmitate

**8 acetyl-CoA molecules**

Additional enzymes that modify fatty acids after synthesis

**Elongases** lengthen chains and **desaturases** introduce double bonds

Fate of newly synthesized fatty acids

They are converted into **triacylglycerols** or **membrane lipids**

Hormone released when blood glucose is high

**Insulin**

Effect of insulin on fat metabolism

Stimulates **fat synthesis** and inhibits **fat breakdown**

Why insulin inhibits fat breakdown

To prevent **futile cycling**, where fats are made and broken down simultaneously

Energy cost of fatty acid synthesis

Fat synthesis is **energetically expensive**, requiring significant ATP input

Hormone released when blood glucose is low

**Glucagon**

Effect of glucagon on fat metabolism

Stimulates **fat breakdown**

Target enzyme stimulated by glucagon

**Lipase** in adipose tissue

What happens to fats when glucagon is active

Fats are broken down into **acetyl-CoA** for energy production

What happens to acetyl-CoA during prolonged fasting

Acetyl-CoA is diverted to **ketone body synthesis**

Role of acetyl-CoA in metabolism

Acetyl-CoA is a **central metabolic intermediate** used for energy production and biosynthesis

Additional biosynthetic role of acetyl-CoA

It serves as a precursor for **cholesterol synthesis**

Key enzyme involved in cholesterol synthesis regulation

**HMG-CoA reductase**

Clinical relevance of HMG-CoA reductase

It is the target of **statin drugs** used to lower cholesterol

How proteins can be used as an energy source

Amino acids are broken down into **pyruvate, acetyl-CoA, or CAC intermediates**

Why protein breakdown can support metabolism

These products enter **glycolysis or the citric acid cycle**

What happens when blood glucose is low overall

Fatty acids are **broken down** to produce energy

What happens when blood glucose is high overall

Fatty acids are **synthesized and stored**

Role of adipose tissue in metabolism

Stores fatty acids as **triacylglycerols**

Why fat storage is beneficial

It provides a **long-term energy reserve**

Why fatty acids are efficient energy stores

They contain **large amounts of reduced carbon**, producing large amounts of ATP upon oxidation

Why metabolism switches between fat synthesis and breakdown

Hormonal regulation prevents **energy waste and futile cycles**

Why beta oxidation generates NADH and FADH₂

Because fatty acids are **oxidized**, releasing electrons

Why fatty acids are shortened two carbons at a time

Each cycle removes a **two-carbon acetyl-CoA unit**

Why ketone bodies are produced during starvation

To supply the **brain with fuel when glucose is unavailable**

Why fatty acids cannot directly fuel the brain

They **cannot cross the blood-brain barrier**

Why NADPH is used instead of NADH in fatty acid synthesis

NADPH is specialized for **reductive biosynthesis**

Why insulin stimulates fat synthesis

High glucose signals **energy abundance**

Why glucagon stimulates fat breakdown

Low glucose signals **energy demand**

Why fatty acid synthesis and breakdown cannot occur simultaneously

This would waste energy through **futile cycling**

Why acetyl-CoA is a central metabolic hub

It links **carbohydrate, fat, and protein metabolism**

Why ketone bodies are considered survival fuels

They allow **brain energy production during prolonged fasting**