🔬Biological Chemistry I Unit 9 – Fatty Acids and Lipids

What Are Fatty Acids and Lipids?

• Fatty acids are long-chain carboxylic acids consisting of a hydrocarbon chain with a carboxyl group (-COOH) at one end
• Lipids are a diverse group of hydrophobic organic molecules that include fats, oils, waxes, and sterols
• Fatty acids serve as building blocks for more complex lipids such as triglycerides, phospholipids, and sphingolipids
• Lipids play crucial roles in energy storage, cell membrane structure, insulation, and signaling
• Fatty acids can be saturated (single bonds between carbon atoms) or unsaturated (one or more double bonds)
  • Saturated fatty acids have higher melting points and are solid at room temperature (butter)
  • Unsaturated fatty acids have lower melting points and are liquid at room temperature (olive oil)
• Essential fatty acids (linoleic acid and alpha-linolenic acid) cannot be synthesized by the human body and must be obtained through diet

Structure and Classification

• Fatty acids are classified based on the length of their hydrocarbon chain and the presence or absence of double bonds
  • Short-chain fatty acids have 2-6 carbon atoms
  • Medium-chain fatty acids have 8-12 carbon atoms
  • Long-chain fatty acids have 14-22 carbon atoms
• Saturated fatty acids have no double bonds and a straight hydrocarbon chain (palmitic acid, stearic acid)
• Monounsaturated fatty acids (MUFAs) have one double bond in their hydrocarbon chain (oleic acid)
• Polyunsaturated fatty acids (PUFAs) have two or more double bonds in their hydrocarbon chain (linoleic acid, arachidonic acid)
  • Omega-3 fatty acids have their first double bond at the third carbon from the methyl end (alpha-linolenic acid, EPA, DHA)
  • Omega-6 fatty acids have their first double bond at the sixth carbon from the methyl end (linoleic acid, arachidonic acid)
• The double bonds in unsaturated fatty acids can be in cis or trans configuration, affecting their shape and properties
• Triglycerides are composed of three fatty acids esterified to a glycerol backbone

Biological Functions

• Fatty acids and lipids serve as a concentrated source of energy, providing 9 kcal/g compared to 4 kcal/g for carbohydrates and proteins
• Triglycerides stored in adipose tissue are the primary long-term energy reserve in the body
• Phospholipids and cholesterol are major components of cell membranes, regulating fluidity, permeability, and signaling
• Lipids provide insulation and protection for vital organs (subcutaneous fat, myelin sheath)
• Fatty acids are precursors for the synthesis of eicosanoids (prostaglandins, leukotrienes, thromboxanes), which are important signaling molecules involved in inflammation, blood clotting, and smooth muscle contraction
• Lipids serve as carriers for fat-soluble vitamins (A, D, E, and K) and facilitate their absorption
• Cholesterol is a precursor for the synthesis of steroid hormones (estrogen, testosterone, cortisol) and bile acids

Metabolism and Energy Storage

• Fatty acid synthesis occurs in the cytosol, primarily in the liver and adipose tissue
  • Acetyl-CoA is the primary substrate for fatty acid synthesis
  • The enzyme fatty acid synthase catalyzes the sequential addition of two-carbon units to form palmitic acid (16:0)
• Beta-oxidation of fatty acids occurs in the mitochondria and peroxisomes, breaking down fatty acids to generate acetyl-CoA for the citric acid cycle and ATP production
  • Carnitine palmitoyltransferase I (CPT-I) is the rate-limiting enzyme for fatty acid oxidation, shuttling fatty acids into the mitochondria
• Triglycerides are synthesized by esterifying three fatty acids to a glycerol backbone, primarily in the liver and adipose tissue
• Lipolysis is the breakdown of triglycerides into glycerol and free fatty acids, which can be released into the bloodstream for energy utilization by other tissues
• Ketogenesis occurs when fatty acid oxidation rates exceed the capacity of the citric acid cycle, leading to the production of ketone bodies (acetoacetate, beta-hydroxybutyrate) as an alternative fuel source for the brain and heart during prolonged fasting or low-carbohydrate diets

Membrane Composition and Function

• Cell membranes are composed of a phospholipid bilayer with embedded proteins, cholesterol, and glycolipids
• Phospholipids have a hydrophilic head group and two hydrophobic fatty acid tails, allowing them to form a bilayer structure in aqueous environments
  • The most common phospholipids are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol
• The fatty acid composition of membrane phospholipids influences membrane fluidity and permeability
  • Shorter and unsaturated fatty acids increase membrane fluidity, while longer and saturated fatty acids decrease fluidity
• Cholesterol modulates membrane fluidity and stability, preventing crystallization of fatty acids at low temperatures and reducing permeability
• Membrane proteins are embedded in the phospholipid bilayer and perform various functions such as transport, signaling, and enzymatic activity
• Glycolipids, consisting of a lipid attached to a carbohydrate, are found on the extracellular side of the membrane and play a role in cell recognition and adhesion

Signaling Molecules and Hormones

• Eicosanoids are signaling molecules derived from 20-carbon polyunsaturated fatty acids (arachidonic acid, EPA)
  • Prostaglandins are involved in inflammation, pain sensation, and smooth muscle contraction
  • Leukotrienes are mediators of inflammation and play a role in asthma and allergic reactions
  • Thromboxanes are involved in platelet aggregation and vasoconstriction
• Steroid hormones (estrogen, testosterone, cortisol) are derived from cholesterol and regulate various physiological processes such as reproduction, metabolism, and stress response
• Vitamin D is a steroid hormone synthesized from cholesterol in the skin upon exposure to UV light, and it regulates calcium and phosphate homeostasis
• Sphingolipids (ceramide, sphingosine) are involved in cell signaling pathways regulating cell growth, differentiation, and apoptosis
• Endocannabinoids (anandamide, 2-arachidonoylglycerol) are lipid-based neurotransmitters that bind to cannabinoid receptors and modulate pain, appetite, and memory

Health Implications and Disorders

• Obesity is characterized by excessive accumulation of adipose tissue and is associated with increased risk of metabolic disorders such as type 2 diabetes, cardiovascular disease, and certain cancers
• Atherosclerosis is the buildup of plaque in the arterial walls, containing cholesterol, fatty acids, and calcium, leading to narrowing of the arteries and increased risk of heart attack and stroke
• Fatty liver disease (hepatic steatosis) is the accumulation of triglycerides in the liver, which can lead to inflammation, fibrosis, and cirrhosis
• Essential fatty acid deficiency can result in dermatitis, growth retardation, and neurological abnormalities
• Inborn errors of fatty acid oxidation (medium-chain acyl-CoA dehydrogenase deficiency) can cause hypoglycemia, liver dysfunction, and cardiomyopathy
• Lipid storage disorders (Gaucher disease, Niemann-Pick disease) are characterized by the accumulation of specific lipids in lysosomes due to enzyme deficiencies
• Dysregulation of eicosanoid production is implicated in inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and asthma

Lab Techniques and Analysis

• Lipid extraction techniques (Folch method, Bligh and Dyer method) use organic solvents (chloroform, methanol) to separate lipids from biological samples
• Thin-layer chromatography (TLC) is used to separate and identify different lipid classes based on their polarity and interaction with a stationary phase
• Gas chromatography (GC) is used to separate and quantify fatty acids after derivatization to volatile methyl esters
• High-performance liquid chromatography (HPLC) is used to separate and quantify various lipid classes based on their interaction with a stationary phase and a mobile phase
• Mass spectrometry (MS) is used to identify and quantify lipids based on their mass-to-charge ratio, often coupled with chromatographic techniques (GC-MS, LC-MS)
• Nuclear magnetic resonance (NMR) spectroscopy is used to determine the structure and composition of lipids based on the magnetic properties of their nuclei
• Enzyme assays (lipase, phospholipase) are used to measure the activity of lipid-metabolizing enzymes in biological samples
• Fluorescent probes (Nile Red, BODIPY) are used to visualize and quantify lipid droplets in cells and tissues using microscopy techniques