OVERVIEW: ANABOLISM VS CATABOLISM (THE MASTER FRAME)

• Anabolism = building and storing (fed state, insulin dominant)

• Catabolism = breaking down and releasing energy (fasting/stress state, insulin low)

The body is never doing everything at once.
Hormones-especially insulin, glucagon, cortisol, and catecholamines-decide which pathway dominates.

1. Glucose Catabolism (Carbohydrate Metabolism)

Glucose is the preferred immediate fuel, especially for the brain and RBCs.

A. Digestion & Absorption

• Dietary carbohydrates → monosaccharides (mostly glucose)

• Absorbed in the small intestine → enter bloodstream

• Rising blood glucose → pancreatic insulin secretion

 This is the fed/anabolic signal

B. Cellular Uptake (Insulin-Dependent)

• Insulin binds to insulin receptors

• Activates intracellular signaling

• GLUT4 transporters move to the membrane

• Glucose enters muscle and adipose cells

(Brain and RBCs do not require insulin for glucose uptake.)

C. Catabolic Energy Pathways of Glucose

Once inside the cell, glucose undergoes stepwise catabolism:

1. Glycolysis (cytoplasm)

• Glucose → pyruvate

• Produces:

  • 2 ATP

  • NADH

• Does not require oxygen

2. Pyruvate → Acetyl-CoA (mitochondria)

• Occurs via pyruvate dehydrogenase

• Requires oxygen

• Irreversible step

This commits glucose to full oxidation.

3. Krebs Cycle + Electron Transport Chain

• Acetyl-CoA enters Krebs cycle

• Generates NADH and FADH₂

• These drive oxidative phosphorylation

• Produces large ATP yield

End result of glucose catabolism:
Glucose → CO₂ + H₂O + ~30–32 ATP

2. Protein Catabolism (Amino Acid Metabolism)

Protein is structural first, fuel second.

The body turns to protein only when glucose is insufficient (fasting, illness, starvation).

A. Digestion

• Proteins → amino acids (AAs)

B. Catabolic Trigger

• Low insulin

• High glucagon/cortisol

• Prolonged fasting, stress, or illness

Muscle protein breakdown increases

C. Deamination (Liver)

• Amino acids lose nitrogen group

• Nitrogen → ammonia → urea cycle

• Urea excreted by kidneys

This step is obligatory before energy extraction.

D. Carbon Skeleton Utilization

Remaining carbon backbones enter metabolism as:

• Pyruvate

• Acetyl-CoA

• Krebs cycle intermediates

These feed directly into ATP generation.

End result of protein catabolism:
Amino acids → ATP + urea

Excessive protein catabolism = muscle wasting

3. Fat Catabolism (Lipid Metabolism)

Fat is the primary long-term energy reservoir and the dominant fuel during fasting.

A. Hormonal Trigger

• Low insulin

• High glucagon, epinephrine, cortisol

Fat cells activate lipolysis

B. Mobilization

• Triglycerides →

  • Free fatty acids (FFAs)

  • Glycerol

FFAs travel bound to albumin → liver & muscle

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C. Beta-Oxidation (Mitochondria)

• FFAs chopped into 2-carbon units

• Each cycle produces:

  • Acetyl-CoA

  • NADH

  • FADH₂

Acetyl-CoA enters Krebs cycle → ETC → ATP

D. Ketogenesis (Prolonged Fasting / Low Carbs)

When glucose is low:

• Liver converts excess Acetyl-CoA into ketone bodies

  • β-hydroxybutyrate

  • Acetoacetate

Ketones fuel:

• Brain

• Heart

• Skeletal muscle

End result of fat catabolism:
Fat → massive ATP yield (far greater than glucose)

4. Insulin Secretion: The Metabolic Switch

Insulin determines whether the body is in storage or breakdown mode.

A. Site

• Beta cells of pancreatic islets

B. Trigger

• Rising blood glucose after meals

C. Step-by-Step Physiology

1. Glucose enters beta cells

Via GLUT2 transporters

2. Glucose metabolism increases ATP

ATP rises inside the cell

3. ATP closes K⁺ channels

• ATP-sensitive potassium channels close

• Cell membrane depolarizes

4. Ca²⁺ channels open

• Calcium influx occurs

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5. Insulin is released

• Calcium triggers vesicle fusion

• Insulin enters bloodstream

D. Biphasic Insulin Release

1. First phase: rapid release of stored insulin

2. Second phase: slower synthesis and release

⚠️ Loss of first phase = early sign of type 2 diabetes

5. Integrated Metabolic States

Fed State (Anabolic)

• High insulin

• Glucose uptake ↑

• Glycogen synthesis ↑

• Fat storage ↑

• Protein synthesis ↑

Fasting State (Catabolic)

• Low insulin

• Glycogen breakdown

• Lipolysis ↑

• Fatty acid oxidation ↑

• Ketone production ↑

• Protein breakdown (limited, adaptive)

FINAL UNIFYING PRINCIPLE

Insulin is the master regulator:

• High insulin → store energy

• Low insulin → release and burn energy

Catabolism is not pathological-
it is essential for survival, fasting, healing, and metabolic flexibility.