Fats as the primary energy reserve
During active digestion (the absorptive state), the body stores excess nutrients as fats, which are deposited in specialized cells called adipocytes. When fasting begins or a person engages in prolonged physical work, these reserves are actively utilized.
Fats are the highest-calorie substances in the human body. This colossal energy density is explained by the chemical structure of fatty acids: their molecules are the most reduced because they contain a large number of -CH2- bonds. That is why the energy yield from their oxidation is more than twice that of carbohydrates (9.7 kcal versus 4.7 kcal per gram of substance).
Activation cascade: the adenylate cyclase system
Fat mobilization does not happen spontaneously; it is a strictly regulated hormonal process. The main stimulants are glucagon and adrenaline. When they bind to specific receptors on the adipocyte membrane, a complex signal transduction cascade is triggered inside the cell:
- Receptor activation: The hormone interacts with the receptor, leading to the activation of a G protein.
- Enzyme action: The active G protein stimulates the enzyme adenylate cyclase (AC).
- Second messenger: Adenylate cyclase catalyzes the conversion of ATP into its cyclic form—cAMP.
- Kinase activation: The accumulation of cAMP leads to the activation of Protein Kinase A.
- Phosphorylation: Active Protein Kinase A attaches a phosphate group to hormone-sensitive lipase (HSL), converting it from an inactive form to an active one.
Protective role of perilipin
At rest, before hormones act, active mobilization is impossible not only due to enzyme inactivity. The fat droplets (triacylglycerols) stored in the adipocyte cytoplasm are reliably protected by a special protein—perilipin.
In its dephosphorylated form, perilipin tightly coats the fat droplet, creating a physical barrier and preventing any enzymes from accessing the substrate. However, when a hormonal signal triggers the action of Protein Kinase A, this enzyme phosphorylates not only the lipase but perilipin itself. As a result of phosphorylation, perilipin changes its conformation and detaches from the fat droplet. Only then do the triacylglycerol molecules become fully accessible for breakdown.
The course of the hydrolysis reaction
As soon as the perilipin barrier is removed and HSL is activated, direct lipid hydrolysis begins:
- First stage: Active hormone-sensitive lipase (TAG lipase) cleaves the first fatty acid molecule from triacylglycerol (TAG). This reaction produces diacylglycerol (DAG) and a free fatty acid (R-COOH).
- Completion of the process: The remaining ester bonds in diacylglycerol and monoacylglycerol (MAG) are hydrolyzed by other lipases present in the cell.
The ultimate outcome of this multistep process is the complete breakdown of stored fat to form free fatty acids and a glycerol molecule, which can then be used by the body to produce energy.
Briefly: answers to topical questions
To which organs is glycerol transported and how is it used after lipolysis?
After lipolysis, glycerol travels from the blood to the liver. In the liver, it can be used for gluconeogenesis—the synthesis of glucose, especially during fasting and intense physical exercise.
Stages of glycerol utilization:
- Phosphorylation — free glycerol is converted into glycerol-3-phosphate by the enzyme glycerol kinase, consuming ATP.
- Oxidation — glycerol-3-phosphate is oxidized to dihydroxyacetone phosphate by the enzyme glycerol-3-phosphate dehydrogenase with the reduction of NAD+.
- Glucose synthesis — dihydroxyacetone phosphate is further incorporated into the gluconeogenesis pathway to form glucose.
Adipose tissue lacks glycerol kinase, so free glycerol is not utilized via this pathway there.
To memorize the lipid breakdown cascade, use the acronym "G/A – AC – cAMP – PKA – HSL" (Glucagon/Adrenaline → Adenylate Cyclase → cAMP → Protein Kinase A → Hormone-Sensitive Lipase).
Class and exam questions
In which cells does fat mobilization take place?
The mobilization process (lipolysis) occurs exclusively inside specialized fat cells—adipocytes—where triacylglycerols are stored during the fed state.
Why does fat oxidation yield significantly more energy than carbohydrate oxidation?
Fatty acids are the most reduced molecules in the body. They contain a large number of -CH2- bonds, which ensures the release of 9.7 kcal upon the oxidation of 1 gram of fat.
How does perilipin block fat breakdown at rest?
In the absence of a hormonal signal, perilipin is in a dephosphorylated form and physically coats the fat droplets, blocking access of enzymes to triacylglycerols.
Which enzyme catalyzes the initial fatty acid cleavage reaction?
The cleavage of the first fatty acid from the triacylglycerol molecule is carried out by hormone-sensitive lipase (HSL), which transitions to the active form after phosphorylation.
What else to study on this topic
- Mechanism of DAG and MAG hydrolysis by other intracellular lipases
- Metabolic fate of free fatty acids after exiting the adipocyte
- Pathways of glycerol utilization in body tissues
- Comparison of lipid metabolism in the absorptive state and during fasting
Master the entire topic in the "Biochemistry" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Fat mobilization" and 3,616 other subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 115 video lessons on the subject
Other topics in the «Lipid metabolism» section
Free video lessons: biochemistryShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.