BIO4232 Ch. 19.1 Metabolic Integration at the Physiologic Level

Energy balance

Refers to the ratio of energy input in an organism to the amount of energy it expends.

• Calories consumed/day (input) = Calories expended/day (output).

Liver

This organ is the glucose regulator.

• Rest fuel: fatty acids

• Fuel stored: glycogen

• Fuel exported: glucose, KB, and VLDL

Adipose tissue

This organ is involved in homeostasis regulation and secretes adipokines.

• Rest fuel: glucose

• Fuel stored: TAGs

• Fuel exported: fatty acids

Skeletal muscle

This organ is involved in movement.

• Rest fuel: fatty acids

• Fuel stored: glycogen

• Fuel exported: lactate and alanine

Brain

This organ is the control center.

• Rest fuel: glucose

• Fuel stored: n/a

• Fuel exported: n/a

Cardiac muscle

This organ pumps blood.

• Rest fuel: fatty acids, KB, and glucose

• Fuel stored: n/a

• Fuel exported: n/a

Kidneys

This organ is involved in glucose synthesis for export and filtration.

• Rest fuel: fatty acids

• Fuel stored: n/a

• Fuel exported: glucose (under fasting conditions)

Portal vein

A vein that carries blood from the gastrointestinal tract and the spleen to the liver, facilitating the inactivation of dietary toxins from the liver.

Creatine kinase

An enzyme that catalyzes a reversible reaction interconverting ATP and phosphocreatine using ADP and creatine as substrates.

Phosphocreatine

A molecule in muscle cells that is used to carry out substrate-level phosphorylation to generate ATP; mobilizes energy reserve in skeletal muscle, heart, and brain tissues under anaerobic conditions.

Glucokinase (HK IV)

This hexokinase is only expressed in the liver and has a high Km value, meaning it’s only active under high [glucose].

• Not inhibited by G6P → allows liver to keep phosphorylating glucose for storage.

Metabolic homeostasis

The process of maintaining optimal metabolite concentrations and managing chemical energy reserves within an organism.

6 primary functions (for homeostasis)

1. Liver must export glucose, KB, & TAGs to peripheral tissues.

2. Brain must constantly receive glucose.

3. Cardiac muscle uses FA, KB, and some glucose.

4. Exchange of FA & TAGs between the liver and adipose via the TAG cycle must occur.

5. Skeletal muscle uses glucose and FA for ATP synthesis, while exporting lactate.

6. Gln and Ala removes excess nitrogen, which is converted into urea.

Triacylglycerol cycle

A two-component system for keeping fatty acids in circulation. FA and TAGs circulate between adipose tissue and the liver, while within adipocytes, FA and TAGs undergo interconversion.

• Dependent on glycerol-3-phosphate.

Systemic component (TAG cycle)

Cycles FA between adipose and the liver in the form of FA-bound albumin or in lipoprotein particles.

Intracellular component

Cycles FA in the form of cytosolic FFA and TAGs stored in lipid droplets.

Liver (response to insulin)

Released by pancreatic beta-cells, causing glycogen and FA synthesis.

Liver (response to glucagon)

Released by pancreatic alpha-cells, causing GNG, glycogen degradation, and FA export.

Adipose and skeletal muscle (response to insulin)

Stimulates glucose uptake by increasing [GLUT4], causing glycogen synthesis.

Adipose (response to glucagon)

Stimulates FA export via TAG hydrolysis.

Brain (response to insulin)

Hypothalamus signals a decrease in appetite.

Liver vs sk. muscle (response to insulin)

1. GLUT4 is the glucose transporter of muscle & adipose, which is translocated to the cell surface in response to hormonal signaling. While GLUT2 is used by the liver & pancreas and is independent of hormonal signaling.

2. Muscle cells lack G6Pase and FA synthase, so they can't export FA or glucose.

3. Muscle is 30x greater than liver mass so glucose uptake via muscle in the primary mechanism to reduce glucose levels.

PPAR nuclear receptor proteins

Transcription factors that regulate genes involved in lipid and glucose metabolism.

• FA binds to the receptor → increased beta-oxidation.

PPAR-gamma

Receptors found in the liver & adipose, stimulating lipid synthesis and storage, activated by thiazolidinediones.

PPAR-alpha

Receptors found in the liver, heart, & skeletal muscle, responsible for activating genes that stimulate lipid uptake and oxidation. Activated by FA & eicosanoids.

PPAR-delta

Receptors found in the liver and muscle, responsible for activating genes that stimulate FA ox and mitochondrial uncoupling.

Mobilization of fuel under starvation

• Stable [glucose] because of GNG.

• Flux is altered because of ketogenesis: increased FA and KB.

• Protein becomes a major energy source: increased urea.