Biochem 2 - Week 1

Week 1: Lipids and Membranes

Fatty Acid Compounds

• Functions:

  • Aid in cellular energy storage.

  • Form membranes.

  • Act as cellular messengers (hormones, electron carriers, pigments).

• Nomenclature for Unbranched Fatty Acids:

  • Described by chain length and number of double bonds (e.g., 12:1).

  • Numbering begins at the carboxyl carbon.

  • Double bond positions indicated by ∆ and a superscript.

Polyunsaturated Fatty Acids

• Contain more than one double bond in their backbone.

• Omega-3 Fatty Acids:

  • Double bond located between C-3 and C-4 relative to the most distant carbon (ω).

• Omega-6 Fatty Acids:

  • Double bond located between C-6 and C-7 relative to ω.

• Α-linolenic Acid:

  • A PUFA that must be obtained from the diet.

  • Used to synthesize eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Triacylglycerols

• Simplest lipids constructed from fatty acids (three fatty acids linked to glycerol with ester linkages).

• Provide stored energy and insulation (found in lipid droplets in adipocytes of animals and seeds of plants).

• Properties:

  • Longer chains and fewer double bonds decrease solubility.

  • Oxidation of fatty acids yields more energy.

  • Fatty acids are lighter than polysaccharides.

Key Takeaways

• Fatty acids are water-insoluble hydrocarbons, essential for energy storage.

• Storage of hydrophobic fats as triacylglycerols is efficient; does not require water for hydration.

• Increased carbon length decreases fat solubility and increases melting temperature.

• Triacylglycerols serve as energy storage and as building blocks for structural components.

Types of Membrane Lipids

• Phospholipids:

  • Composed of two fatty acids joined to the glycerol of sphingosine.

• Glycolipids:

  • Contain simple sugars or complex oligosaccharides at polar ends.

• Archaeal Tetraether Lipid:

  • Consists of two long alkyl chains ether-linked to glycerol at both ends.

• Steroids:

  • Rigid structures consisting of four fused hydrocarbon rings (do not include fatty acids).

Glycerophospholipids

Mempl lipids where 2 fatty acids are ester-linked to the first and second carbon of glycerol with a highly polar group attached to the third carbon through a phosphodiester linkage. This makes glycerophospholipids chiral compounds.

Sphingolipids

• Large class of membrane phospho/glycolipids with:

  • A polar head group and two nonpolar tails.

  • Do not contain glycerol; contain sphingosine or its derivatives.

Sphingomyelins

• A subclass of sphingolipids with either phosphocholine or phosphoethanolamine as their polar head group.

Glycosphingolipids

• Head groups with one or more sugars connected to -OH at C-1 of the ceramide moiety, do not contain phosphates, found largely at the outer face.

  • Cerebrosides:

    • Contain a single sugar linked to ceramide (galactose in neural tissues, glucose in non-neural tissues).

  • Globosides:

    • Glycosphingolipids with 2 or more sugars (D-glucose, D-galactose, N-acetyl-D-galactosamine).

  • Gangliosides:

    • Oligosaccharides as polar head groups with one or more residues of N-acetylneuraminic acid (sialic acid).

    • Defined by the number of sialic acid residues (GM, GD, GT series).

Sphingolipids and Blood Group Antigens

• ABO(H) Blood Group Antigens:

  • Specific glycans on N- or O-glycoproteins/glycolipids on erythrocytes, epithelial and endothelial cells.

  • hh blood group: RBCs lack A, B, and H antigens due to mutation of the FUT1 gene.

Shiga Toxins and E. Coli

• Gb3 Glycosphingolipid:

  • Present on kidney epithelial cells.

• Enterohemorrhagic E. coli (EHEC):

  • STEC acquired through the oral-fecal route or contaminated food/water.

  • Causes severe cramps and bloody diarrhea via cellular effacement.

  • Shiga toxin binds to Gb3, leading to kidney injury and thrombotic responses.

• Process:

  1. Ingestion of STEC/EHEC.

  2. Replication and attachment.

  3. Shiga toxin secretion and entry into bloodstream.

  4. Binding to Gb3 receptors on kidney cells.

  5. Internalization of Gb3-Toxin.

  6. Retrotranslocation through Golgi and ER.

  7. Activation of Shiga toxin via proteolysis.

  8. Cleavage of 28S rRNA.

  9. Induces cell death, kidney injury, and thrombotic responses.

Sterols

• Structural lipids in most eukaryotic cell membranes, contain a polar head group and an alkyl side chain.

• Bile Acids:

  • Polar derivatives of cholesterol; emulsify dietary fats for improved accessibility by digestive lipases.

• Cholesterol:

  • Major sterol in animal tissues, amphipathic (contains polar head group and nonpolar hydrocarbon body).

  • Membrane constituent; related to stigmasterol in plants and ergosterol in fungi.

Steroids

• Oxidized derivatives of sterols that lack the D-ring alkyl chain from cholesterol; they are more polar and can travel through the bloodstream to target tissues.

Membrane States

• Acyl Groups:

  • Organized to form:

    1. Liquid-ordered (Lo) state: gel-like state, limited motion of molecules.

    2. Liquid-disordered (Ld) state: individual hydrocarbon chains in constant motion.

Membrane Lipid Transport Proteins

• Flippases:

  • Catalyze translocation of amino-phospholipids (PE, PS) from extracellular to cytoplasmic leaflets; consume ~1 ATP per molecule.

• Floppases:

  • Move phospholipids and sterols from cytoplasmic to extracellular leaflets (ATP-dependent).

• Scramblases:

  • Move any membrane phospholipid across the bilayer, not ATP-dependent; some require Ca2+.

Key Concepts

1. Main lipids of biological membranes: phospholipids, glycolipids, sphingolipids, sterols.

2. Membrane lipids are generally amphipathic, containing a polar head group and hydrophobic core.

3. Sphingolipids play crucial roles in animal membranes and act as structural receptors.

4. Human blood groups are defined by sphingolipids with specific saccharide head groups.

5. Gb3 is a receptor for bacterial toxins, causing diseases like hemolytic uremic syndrome.

6. Fatty acid composition impacts membrane fluidity and localization.