- Lipids are a large group of substances united by hydrophobicity.
- Some have both water-repellent and water-loving areas → amphiphilic molecules.
- They are part of membranes, store energy, protect organs and participate in signaling pathways.
🧪 Lipid classification
🔹 By the possibility of hydrolysis in an alkaline environment:
- Saponifiable (can be broken down):
- Simple: fats (TAG), waxes, cholesterol esters.
- Complex: phospholipids, glycolipids, sphingolipids.
- Unsaponifiable (cannot be broken down):
- Steroids: cholesterol, hormones, vitamins, bile acids.
🔋 Lipid functions
1. Energy (reserve)
→ TAGs are the body's "batteries": they provide energy during starvation, especially to muscles, liver, and kidneys.
2. Structural
→ Membranes = phospholipids + cholesterol + glycolipids.
→ The state of the membranes affects the work of enzymes (Na⁺/K⁺-ATPase, cytochrome oxidase).
3. Signaling
→ Glycolipids are like antennas, they receive signals.
→ Eicosanoids (fatty acid products) are "tissue hormones".
4. Protective
→ Fat is protection and thermal insulation.
→ Some lipids are involved in inflammation, platelet aggregation.
🧬 Fatty acids (FA) — the key to the properties of lipids
🔹 General properties of FA in humans:
- Even number of carbons
- Chain without branches
- Only cis-double bonds
🔹 Types of FA:
- Saturated (without double bonds)
- → Palmitic (C16), stearic (C18), arachidic (C20)
- Monounsaturated (one double bond)
- → Oleic (C18:1 Δ9)
- Polyunsaturated (2+ double bonds)
- Divided by the position of the first double bond from the tail of the molecule (ω):
- 🌻 ω-6 FA (vitamin F)
- Linoleic (C18:2), γ-linolenic (C18:3), arachidonic (C20:4)
- Source: vegetable oils (sunflower, flaxseed)
- 🐟 ω-3 FA
- α-Linolenic (C18:3), thymnodonic (C20:5), docosahexaenoic (C22:6)
- Source: cold-water fish oil, flaxseed, hemp oil
⚡ Functions of fatty acids
Energy
→ β-oxidation provides energy (especially saturated and monounsaturated FA)
Structure
→ FA determine the fluidity and functions of membranes
Brain and behavior
→ FA C22 and C24 are involved in learning and memory
Raw materials for signals
→ Eicosanoids (from FA C20) = "local hormones"
👣 A story about Eskimos (mnemonics)
🧊 Eskimos eat fatty fish - they don't get heart disease!
→ They have a high level of ω-3 fatty acids → low risk of strokes, heart attacks, thrombosis.
🩺 Indications for use of ω-3
- FA Atherosclerosis, thrombosis
- Diabetes and its complications (retinopathy)
- Fat metabolism disorders
- Arrhythmia, vascular diseases
- 🧠 Scheme (for memorization)
CopyEdit
🔹 Lipids
- Saponifiables
- Simple: TAG, waxes, esters
- Complex: phospho-, glyco-, sphingo-
- Unsaponifiables
- Steroids: cholesterol, hormones, vitamins
🔹 Functions
- 📦 Energy— TAG
- 🧱 Structure— membranes
- 🔔 Signals— glycolipids, eicosanoids
- 🛡 Protection— fat, mediators
🔹 Fatty acids
- Saturated (C16-C20)
- Monounsaturated (Δ9)
- Polyunsaturated:
ω-6: vitamin F, vegetable oils
ω-3: fish, flaxseed oil
📝 Summary
- Lipids are hydrophobic molecules with the functions of energy storage, structure, signaling and protection.
- They are divided into saponifiable and unsaponifiable, simple and complex.
- Fatty acids are the main building blocks of lipids, they determine their properties and functions.
- ω-3 FAs are especially useful: they protect the heart, blood vessels, brain, and participate in the synthesis of tissue hormones.
- They are important for the prevention of diabetes, atherosclerosis, heart attacks and lipid metabolism disorders.
Eicosanoids: General InformationEicosanoids are oxidized derivatives of fatty acids, such as eicosatrienoic (C20:3), arachidonic (C20:4), and timnodonic (C20:5). They play key physiological roles, including effects on inflammation, blood clotting, vascular tone, and more.
Main Groups of Eicosanoids
Prostaglandins (Pg)
- Synthesized in almost all cells except erythrocytes and lymphocytes.
- Functions: regulate smooth muscle tone, body temperature.
- Types: Pg A, B, C, D, E, F.
Prostacyclins (PGI)
- Subtype of prostaglandins.
- Functions: dilate small vessels, inhibit platelet aggregation.
- Synthesized in vascular endothelium, myocardium, uterus, and gastric mucosa.
Thromboxanes (Tx)
- Synthesized in platelets.
- Functions: stimulate platelet aggregation, vasoconstriction.
- Activity decreases with increased double bonds in fatty acids.
Leukotrienes (Lt)
- Synthesized in leukocytes, lungs, spleen, brain.
- Functions: inflammation activation, chemotaxis, bronchoconstriction.
Synthesis of Eicosanoids
Eicosanoid synthesis begins from membrane phospholipids. Various factors (histamine, cytokines) activate phospholipases, which release fatty acids such as arachidonic acid.
Metabolic Pathways
- Cyclooxygenase pathway: synthesis of prostaglandins and thromboxanes.
- Lipoxygenase pathway: synthesis of leukotrienes.
Pharmaceutical Regulation- Glucocorticoids (e.g., prednisone) inhibit all eicosanoid types by suppressing phospholipase A2.
- NSAIDs (e.g., aspirin) inhibit cyclooxygenase, reducing prostaglandin and thromboxane production.
Role of Omega-3Fatty AcidsOmega-3 fatty acids (e.g., from fish) promote the formation of eicosanoids with more double bonds, reducing blood viscosity and improving blood flow, while lowering blood pressure.
Eicosanoid Groups Based on Fatty Acids- Linolenic Acid (C18:3): Pg E1, Tx A1, Lt A3.
- Arachidonic Acid (C20:4): Pg E2, Tx A2, Lt A4.
- Timnodonic Acid (C20:5): Pg E3, Tx A3, Lt A5.
Mnemonics- Prostaglandins (Pg) — "Simple but important functions: pressure, bronchi, temperature."
- Prostacyclins (PGI) — "Simple cycle, expands vessels and prevents platelets from sticking."
- Thromboxanes (Tx) — "Thrombi love narrowed vessels!"
- Leukotrienes (Lt) — "Leukocytes always in action — migration and inflammation."
SummaryEicosanoids are important mediators that regulate many physiological processes, such as inflammation, blood clotting, and vascular tone. They are divided into four main groups: prostaglandins, prostacyclins, thromboxanes, and leukotrienes. Their synthesis depends on fatty acids, and their activity is regulated by hormones and drugs. Omega-3 fatty acids help reduce thrombus formation and improve blood circulation.
🧬 Lipidoses (lipid accumulation diseases)
Lipidoses are genetic disorders in which lipids accumulate in cells due to defects in lysosomal enzymes.
Disease | Defective Enzyme | Accumulated Substance | Symptoms |
Wolman disease | Acid esterase | Cholesteryl esters | Vomiting, steatorrhea, adrenal calcification, death < 6 months |
Schüller-Christian | Unknown | Cholesterol esters | Bone damage, cerebellar ataxia, skin lesions |
Gaucher | β-glucosidase | Cerebrosides | Hepatosplenomegaly, osteoporosis |
Niemann-Pick | Sphingomyelinase | Sphingomyelin | Mental retardation, blindness, death < 2 years |
Tay-Sachs | Hexosaminidase A | Gangliosides | Blindness, dementia, death in infancy |
🧠 Mnemonics:
“Magic Cones Chase Nervous Tigers.”
(Vollmann, Schüller-Christian, Gaucher, Niemann-Pick, Thea-Sachs)
⚡ Triacylglycerols (TAGs) - energy reserve
- Major energy reserves: 16-23% of body weight.
- Composed of: glycerol + 3 fatty acids (more often saturated: palmitic, stearic acids).
Functions:
- Energy (40 days fasting).
- Mechanical protection of organs.
- Heat conservation.
- In infants: main source of energy → needs care from hypothermia.
- Progression:Simple TAGs - same GIs (tripalmitin).
- Mixed TAGs - different GIs (palmityloleoylstearin).
💡 Mnemonic:
“Glycerol + 3 Tails = Batter.”
(Glycerol + GI = energy reserve)
🧪 Burned fats
- Biological: enzymatic → short LCs, ketones → unpleasant odor.
- Chemical (POL): oxygen → peroxides → malonic dialdehyde, etc.
🛡️ Antioxidants: vitamins E, A, C, glutathione, enzymes (catalase, peroxidase, SOD).
🧱 Cholesterol
- Structure: cyclopentane-perhydrophenanthrene + OH → alcohol.
- 25% is esterified in the body.
- Synthesis: 0.5-0.8 g/day (liver, intestine, other cells).
- Daily intake: ~0.4 g (eggs, liver, oil).
- Functions:Membranes - stiffness and viscosity.
- GI transport - as part of LDL/LDL.
- Precursor:Bile acids, hormones, vitamin D.
- Excretion:With bile, with feces - up to 1 g / day.
- Skin, fat - 0.1 g.
- Metabolism to hormones - 0.1 g.
🧠 Mnemonic:
“HC is a SMJ: Builder, Molecule, Fat-soluble factory.”
🍽️ Fat digestion Stages
- Emulsification (bile).
- Hydrolysis (lipases, phospholipases).
- Micelles (fatty acids, MAG, HC).
- Absorption into enterocytes.
- Resynthesis and assembly into chylomicrons, HDL.
👶 In infants, even minimal fats are important - stimulate enzyme secretion.
Lipases:
- Pancreatic lipase + colipase → breakdown of TAG.
- Phospholipases A2, C → breakdown of FL.
- CS esterase → hydrolysis of CS esters.
🧠 Mnemonic:
“EGM-BP.”
(Emulsification → Hydrolysis → Micelles → Absorption → Resynthesis)
🧩 Scheme for memorization
🔁 Fats → 📌 Emulsification (bile) → 🔬 Hydrolysis (lipases, esterases) →⚪ Micelles (HC, LC, MAG) → 🧱 Absorption (enterocytes) → 📦 Resynthesis → Chylomicrons → Bloodstream
✍️ Summary
- Lipidoses - genetic diseases with lipid accumulation (Wolman, Gaucher, Thea-Sachs, etc.).
- TAGs - major form of energy storage, involved in thermoregulation, defense.
- Cholesterol - structural component of membranes and precursor of biologically active substances.
- Burning - result of fat oxidation, biological or chemical.
- Digestion of fats - 5 steps, key role of lipases and bile.
Bile and its composition
- Bile consists of water (97%) and dry residue (3%).
- The dry residue contains:
- Sodium, potassium, bicarbonates, creatinine, cholesterol, phosphatidylcholine.
- Bilirubin and bile acids (secreted by hepatocytes).
- Normal ratio of bile acids, phosphatidylcholine and cholesterol: 65:12:5.
Role of bile
- Neutralization of acidic chyme.
- Emulsification of fats for digestion.
- Provides absorption of fat-soluble vitamins (A, D, E, K).
- Enhances intestinal peristalsis.
- Excretion of excess cholesterol, bilirubin, creatinine, metals and drugs.
Bile formation
- Bile formation is continuous.
- Increased under the influence of n.vagus and meat foods.
- Decrease under the influence of the sympathetic nervous system.
Synthesis of bile acids
- In the liver, primary bile acids (cholic and chenodeoxycholic acids) are synthesized from cholesterol.
- In the intestine, under the action of microflora, they are converted into secondary bile acids (deoxycholic and lithocholic).
Intestinal-hepatic circulation
- Bile acids circulate between the liver and the intestine, providing lipid digestion.
- The loss of bile acids is about 0.5 g/day.
Lipid absorption
- 98% of lipids are absorbed in the small intestine.
- Short-chain fatty acids are absorbed directly into the blood.
- Long-chain fatty acids and cholesterol form micelles with bile acids for absorption.
Lipid resynthesis
- Fatty acids are activated in cells and are used to synthesize cholesterol esters, triacylglycerols, and phospholipids.
Lipid digestion disorders
- Problems with digestion or absorption can lead to steatorrhea.
- Causes include lack of bile, pancreatic lipase, damage to the intestinal wall, excess calcium and magnesium.
Summary
Bile is an important fluid necessary for the digestion of fats. It is composed of water, various ions and compounds such as cholesterol and phosphatidylcholine. It performs several functions: it neutralizes chyme, helps digest fats, aids in the absorption of vitamins, and removes excess cholesterol. Bile acid synthesis occurs in the liver, where cholesterol is converted into primary bile acids. These acids circulate between the liver and the intestines to allow digestion of food. Disturbances in lipid digestion can lead to steatorrhea.
Peculiarities of fat digestion in children
- In infants, the fat emulsion of milk aids digestion, and lingual lipase from Ebner's glands is secreted during suckling and continues its work in the stomach.
- Gastric lipase is more active in infants (due to an acidity of about 5.0), which helps digest fats.
- Pancreatic lipase activity is low before the age of 7 years, reaching a peak only at 8-9 years of age, which limits digestion of dietary fat. Nevertheless, even in the first months of life, children are able to hydrolyze almost 100% of fat and absorb 95%.
- Bile acids in the bile of infants triple by age 1 year.
Fatty acid and lipid metabolism
- Fatty acids form the basis of lipids, and lipid metabolism is the metabolism of fatty acids. Their fate depends on type (saturated or polyunsaturated) and cellular conditions (presence or absence of energy).
- During the absorptive period, fatty acids enter with chylomicrons into tissues that have lipoprotein lipase on the capillary endothelium.
- In the liver, fatty acids can be synthesized from excess glucose and then esterified into TAG and transported to tissues with lipoproteinlipase.
- In adipose tissue cells, fatty acids are stored as TAG; if lipoproteinlipase is not present, fatty acid is delivered via albumin.
Effects of fasting and exercise
- Starvation and exercise activate the breakdown of TAG (lipolysis) and the release of fatty acids, which are transported to muscle tissue to provide work.
- Under fasting conditions, fatty acids are used for ketogenesis (formation of ketone bodies) in the liver, which are then used as energy.
- Fat mobilization and oxidationMobilization of TAG involves activation of TAG lipase (the main enzyme of lipolysis), transport of fatty acids with albumin, their entry into cells, activation via HS-CoA attachment, and oxidation in mitochondria.
- Depending on the physiological state, fatty acids can be used to synthesize energy or ketone bodies.
Mnemonics for fatty acid metabolism:
- Three Stages: Synthesis (liver), Storage (adipose tissue), Combustion (muscle and cells).
Mnemonic for lipolysis:
- GOLD = Glucagon, Fat oxidation, Lipolysis, Enzyme activation (TAG lipase).
Schema to memorize:
- Food intake -> Fats are emulsified -> Gastric lipase is activated.
- Pancreatic lipase -> Digests fats in the 12 ileum.
- Starvation/exercise -> Lipolysis -> Fatty acids enter the blood with albumin.
- Lipogenesis in liver -> TAGs are transported to adipose tissue.
Summary
This outline reveals the features of fat digestion in children, metabolism of fatty acids in the body, effects of fasting and exercise on lipid metabolism. It explains the role of lipases in fat digestion and storage, and provides mnemonics and diagrams to better understand key processes.
Fatty acid oxidation (β-oxidation)
- The basic steps of β-oxidation. Fatty acid oxidation is the process by which energy from fatty acids is converted into ATP bond energy. It occurs in mitochondria, with the exception of nerve cells. Key point: β-oxidation is linked to the tricarboxylic acid cycle and the respiratory chain. The third carbon (β-position) of the fatty acid is oxidized, releasing an acetyl group that goes into the Krebs cycle.
- Process steps: Fatty acid activation: The fatty acid is activated in the cytosol by combining with coenzyme A to form acyl-S-CoA. This is a high-energy compound.
- Transport across the mitochondrion: Acyl-S-CoA cannot pass through the mitochondrial membrane, so it binds to carnitine, which transports it across the membrane. This process requires carnitine acyltransferases I and II.
- β-oxidation: A cycle of 4 reactions occurs in the mitochondria: oxidation, hydration, reoxidation, and acetyl-S-CoA detachment. These reactions are repeated until two acetyl-S-CoAs are formed.
- Energy balance: Several molecules of ATP are formed during β-oxidation. The number of molecules depends on the number of carbons in the fatty acid and the oxidation cycles.
Example of palmitic acid oxidation (C16)Palmitic acid has 16 carbons, which results in the formation of 8 molecules of acetyl-S-CoA.
- From these 8 molecules of acetyl-S-CoA, 80 molecules of ATP are formed (10 ATP per molecule).
- In 7 cycles of β-oxidation, 28 ATP molecules are formed.
- 2 molecules of ATP are consumed for activation.
- Total: 80 + 28 - 2 = 106 ATP molecules.
Oxidation of unsaturated fatty acids
- The oxidation of unsaturated fatty acids requires additional enzymes that move the double bonds in fatty acids from the γ- to the β-position.
- As a result, no FADH2 will be formed in the first reaction, which reduces the amount of energy produced in the process.
Oxidation of “odd” fatty acids
- Odd fatty acids such as nonadecylic acid, when oxidized, form propionyl-S-CoA, which is then converted to succinyl-S-CoA, participating in the Krebs cycle.
- The vitamins biotin (B6) and cobalamin (B12) are required for these processes.
Scheme to memorize:
Stages of β-oxidation:
- Activation → Fatty acid + coenzyme A → Acyl-S-CoA.
- Transport across membrane → Acyl-S-CoA + carnitine → carnitine acyl synthetase → acyl-S-CoA
- β-oxidation cycle → 4 reactions (oxidation, hydration, re-oxidation, acetyl-S-CoA detachment)
- Energy balance → ATP formation
Memorization mnemonic: Activation → Transport → Cycle → Energy. (ATCE)
Summary of synopsis
- β-oxidation is a process of energy conversion from fatty acids to ATP that occurs in mitochondria.
- It involves fatty acid activation, transport across the membrane by carnitine, an oxidation cycle to form acetyl-S-CoA, and ATP production.
- Example: oxidation of palmitic acid (C16) results in the formation of 106 molecules of ATP.
- Oxidation of unsaturated and odd fatty acids has its own peculiarities and requires additional enzymes and vitamins.
Ketone bodies and their synthesis
Ketone bodies are a way of transporting the acetyl group under conditions of energy deficiency, especially when blood glucose levels are low. They are formed in the liver from fatty acids and include three major compounds: acetoacetate, 3-hydroxybutyrate, and acetone.
Conditions for the formation of ketone bodies:
- The entry of large amounts of fatty acids into the liver (e.g., in starvation, type I diabetes, or prolonged exercise).
- In starvation or hypoglycemia, gluconeogenesis is activated and fatty acids are oxidized to ketone bodies because oxaloacetate is used for glucose synthesis rather than CTC.
Features of ketonemia in children:
- In infants, ketonemia develops more rapidly and with greater intensity.
- In the first days of life, acetoacetate levels are elevated due to active mobilization of fat stores.
- In children under 7 years of age, the synthesis of ketone bodies is accelerated, which may lead to ketoacidosis.
Synthesis of ketone bodies:
- The process of ketone synthesis occurs in the mitochondria of the liver.
- Acetoacetate is either reduced to 3-hydroxybutyrate or decarboxylated to acetone.
- All three ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone) are excreted into the blood and can be utilized by other tissues, especially the myocardium and adrenal cortex.
Metabolism in diabetes:
- In type I (insulin-dependent) diabetes, ketonemia is increased due to low insulin levels and elevated glucagon, which inhibits the TCA cycle (tricarboxylic acid cycle) and promotes ketone synthesis.
- In type II (insulin-independent) diabetes, there is normal metabolism of acetyl-SCoA, which is either burned in the CTC or used to synthesize fats and cholesterol.
Hormonal and metabolic regulation:
- Insulin and glucagon regulate fatty acid synthesis and oxidation through enzyme phosphorylation/dephosphorylation.
- Under conditions of excess energy (e.g., elevated glucose levels), fatty acid synthesis occurs, and under conditions of energy deficiency, β-oxidation is activated.
Fatty acid synthesis:
- Fatty acid biosynthesis begins with acetyl-SCoA, which is transported from the mitochondria to the cytosol where it is converted to malonyl-SCoA.
- Based on malonyl-SCoA, fatty acids such as palmitic acid (C16) are synthesized.
- Fatty acids can elongate to C18 or C20 in the endoplasmic reticulum.
Diagram to make it easier to memorize:
Process of ketogenesis:
- Fatty acids → Acetyl-SCoA → CTC (if oxaloacetate is available) or ketone bodies.
- In starvation: low insulin → ketogenesis (instead of CTC).
Fatty acid synthesis:
- Glucose → Pyruvate → Acetyl-SCoA → CTC (if oxaloacetate available) or fatty acid biosynthesis.
- Acetyl-SCoA → Malonyl-SCoA → Palmitic acid (C16).
Summary of Content:
Ketone bodies are formed in the liver during glucose deficiency and serve as a source of energy for tissues. The synthesis of ketone bodies is activated by starvation, diabetes, exercise, and alcohol poisoning. Children are characterized by an increased tendency to ketonemia and ketonuria. The process of fatty acid synthesis is activated by excess glucose and results in the formation of fatty acids such as palmitic acid.
Synthesis of TAG and FL 1
- Formation of glycerol-3-phosphateIn the absorptive period, glycerol from the intestine is phosphorylated by glycerol kinase in the liver. In tissues such as muscle and adipose tissue, glycerol-3-phosphate is formed from dioxyacetone phosphate, a metabolite of glycolysis.
- Synthesis of phosphatidic acid (PA)Fatty acids are activated in an ATP-dependent reaction and converted to acyl-SCoA. In the presence of glycerol-3-phosphate and acyl-SCoA, phosphatidic acid is synthesized. The fatty acid composition of FA determines its further utilization: Saturated and monounsaturated fatty acids (e.g., oleic acid) are used for TAG synthesis.Polyunsaturated fatty acids (e.g. linolenic acid) lead to the formation of phospholipids.
- Synthesis of TAGs (Triacylglycerols)TAGs serve as energy stores. TAG synthesis is regulated only by the availability of substrate. In the liver, TAGs are evacuated into tissues via LDL, transporting fatty acids.
- Lipogenesis (fat synthesis)TAGs are synthesized when there is an excess of acetyl-SCoA, which occurs with carbohydrate or ethanol consumption. Synthesis increases with increasing concentrations of fatty acids and insulin.
- Phospholipid synthesisThe synthesis of phospholipids requires the activation of the components: choline and ethanolamine.
- There are two synthesis pathways:
- Rescue pathway (reuse of choline and ethanolamine).
- Main pathway where choline/ethanolamine are synthesized during phospholipid formation.
6. Lipid transportLipids are transported as part of lipoproteins, which allows them to be soluble in the blood.
- There are four classes of lipoproteins: HDL, LDL, LDL, LDL-ONP, and chylomicrons.
- Each class has a different function in transporting fatty acids, cholesterol, and phospholipids.
- SummaryGlycerol-3-phosphate is formed in the liver and other tissues, where it is used to synthesize phosphatidic acid and TAGs.
- TAGs are synthesized in the liver and transported via LDL.
- TAG synthesis is increased with excess carbohydrates and ethanol.
- Phospholipids are synthesized through two pathways: rescue and major pathways.
- Lipids are transported in lipoproteins: chylomicrons transport fats from the intestine, LPLONP and LDL from the liver.
Mnemonic: “Glycerol-3-phosphate - Fatty acid activation - Phosphatidic acid synthesis - Lipogenesis - Phospholipids - Lipoproteins”