OIA1003 INTEGRATED ENERGY METABOLISM

Integrated metabolism

Coordination of carbohydrate, lipid, and protein metabolism across tissues, depending on fed or fasting state.

Key metabolic intermediate

Acetyl-CoA — central hub connecting glycolysis, β-oxidation, amino acid catabolism to TCA, cholesterol, FA synthesis.

Major metabolic pathways

Glycolysis, gluconeogenesis, glycogenolysis, glycogenesis, β-oxidation, lipogenesis, TCA cycle.

Liver’s role

Central distribution organ; receives nutrients from portal vein and regulates storage, conversion, and distribution.

Absorptive state duration

Lasts ~2–4 hours after eating; marked by increased blood glucose, amino acids, and lipids.

Hormonal profile in absorptive state

High insulin, low glucagon → promotes anabolism.

Main energy source in fed state

Glucose — preferred by most tissues.

Brain energy source

Exclusively uses glucose; cannot use fatty acids due to blood-brain barrier.

Glycogen in brain

None — depends on constant glucose supply.

Glucose uptake (muscle)

Increased via GLUT4 (insulin-dependent).

Glycogen storage (muscle)

↑ Glycogenesis for short-term energy.

Protein synthesis (muscle)

↑ Amino acid uptake for protein production.

Fat usage (muscle)

Minimal during fed state; glucose preferred.

Glucose uptake (adipose)

Via GLUT4; converted to G3P for TG synthesis.

TAG formation (adipose)

Via uptake of FAs from VLDL/chylomicrons (via lipoprotein lipase).

Lipogenesis (adipose)

↑ FA and TAG synthesis; ↓ lipolysis due to insulin.

Carbohydrate metabolism (liver)

↑ Glucose uptake → ↑ glycogenesis, glycolysis, PPP; ↓ gluconeogenesis.

Lipid metabolism (liver)

↑ FA synthesis (from acetyl-CoA), ↑ TAG synthesis, ↑ VLDL release.

Amino acid metabolism (liver)

↑ Protein synthesis (temporary), ↑ AA catabolism for gluconeogenic precursors or lipogenesis

Energy status (fed state)

High ATP; biosynthetic (anabolic) pathways dominate.

Metabolic goal (fed state)

Store energy as glycogen (liver/muscle) and TAG (adipose).

Definition of fasting

Begins 4–6 hours post-meal; starvation = prolonged fasting or nutrient deprivation.

Hormonal profile in fasting

↓ Insulin, ↑ Glucagon → catabolism activated.

Main metabolic goals in fasting

Maintain blood glucose

Mobilize alternate fuels (FA, ketone bodies)

Initial energy use (brain)

Exclusively glucose for 1–2 days.

Ketone use (brain)

Starts by day 3 of starvation; eventually major energy source to spare protein.

Energy substrate switch (muscle - starved)

Uses FA and ketones <3 weeks; after 3 weeks, uses mostly FA.

Protein metabolism (muscle - starved)

Early: muscle proteolysis for gluconeogenesis (alanine, glutamine).

Later: proteolysis decreases as brain uses ketones.

Lipolysis (adipose - starvation)

↑ Hormone-sensitive lipase activity (due to low insulin), ↑ FA release.

Glycerol role (adipose starvation)

Used for gluconeogenesis in liver.

Ketogenesis trigger (adipose - starved)

Liver converts excess acetyl-CoA (from FA oxidation) into ketones.

Glycogen stores (liver - starved)

Depleted within ~10–12 hrs.

Gluconeogenesis (liver - starved)

Main glucose source after glycogen is depleted; uses AA, lactate, glycerol.

Fatty acid oxidation (liver - starved)

Major energy source in liver; provides ATP and NADH for gluconeogenesis.

Ketone body synthesis (liver - starved)

Initiated when acetyl-CoA exceeds TCA capacity.

Insulin promotes

Glucose uptake, glycogenesis, glycolysis, lipogenesis, protein synthesis.

Glucagon promotes

Glycogenolysis, gluconeogenesis, lipolysis, ketogenesis.

Tissue specificity

Each tissue responds differently to hormonal changes based on enzyme expression and fuel preference.

Fed state priority

Store energy (glycogen, TAG); build proteins and lipids.

Fasting state priority

Maintain plasma glucose for brain + mobilize FA/ketones for other tissues.