Lipids and Carbohydrates Detailed Notes

Lipids and Carbohydrates

Lipids: Basics

  • Definition of Lipids: Biological molecules generally insoluble in water.
  • Classification:
    • Simple: Yields a maximum of two products upon hydrolysis.
    • Complex: Yields three or more products upon hydrolysis (e.g., Acyl glycerols give glycerol + fatty acids, Glycerophospholipids).
  • Types of Lipids:
    • Storage lipids
    • Structural lipids

Carbohydrates: Basics

  • Definition: Includes structural forms, functional groups, and carbon numbers.
  • Isomerism: Chiral centres, enantiomers, and epimers.
  • Optical Isomers: Anomers.
  • Pyranoses and Furanoses.
  • Conformers.

Lipid Definition

  • Biological molecules that are generally insoluble in water.
  • Broadly divided into:
    • Simple: After hydrolysis, a maximum of two products are produced.
    • Complex: Three or more products produced, e.g., Acyl glycerols (glycerol + fatty acids) and Glycerophospholipids.

Lipidome

  • Concept of the Lipidome: Example: “Flexibility of a Eukaryotic Lipidome – Insights from Yeast Lipidomics”. Klose et al., 2012 PLoS ONE 7(4): e35063.
    • Classification according to structure: Based on IUPAC's proposed system for naming organic molecules (IUPAC: International Union of Pure and Applied Chemistry).
    • 8 classes & numbering system to specify the molecule precisely.

Lipid Classification

  • Classification according to function
    • Storage lipids
    • Structural lipids in membranes
    • Lipids as signals, cofactors, and pigments
  • Definition: cis and trans:
    • cis: The two H atoms are on the same side of the double bond.
    • trans: The two H atoms are on opposite sides.
    • In a cis configuration, the double bond creates a bend or kink in the fatty acid.

Storage Lipids

  • Fats and oils used as stored forms of energy are derivatives of fatty acids.
  • Fatty acids are hydrocarbon derivatives, highly reduced.
  • Oxidation of fatty acids is highly exergonic.

Fatty Acids

  • Carboxylic acids with hydrocarbon chains with 4 to 36 carbons
  • Saturated chains: no double bonds contained between carbons
  • Unsaturated chains: chains containing double bonds between carbons à this affects the structure of the molecule
  • Systematic name: specifies the chain length and number of double bonds
  • Examples:
    • cis-,cis-9,12-octadecadienoic acid (Linoleic Acid): CH3CH2CH2CH2CH2CH=CHCH2CH=CHCH2CH2CH2CH2CH2CH2CH2CH2COOHCH3CH2CH2CH2CH2CH=CHCH2CH=CHCH2CH2CH2CH2CH2CH2CH2CH2COOH
    • CH3−CH2−CH2−CH2−CH2−CH2−CH2−COOHCH3-CH2-CH2-CH2-CH2-CH2-CH2-COOH
    • CH3−CH2−CH=CH−CH2−CH2−CH2−COOHCH3-CH2-CH=CH-CH2-CH2-CH2-COOH

Saturated Fatty Acids

  • Capric acid: C10:0
  • Lauric acid: C12:0
  • Myristic acid: C14:0
  • Palmitic acid: C16:0
  • Stearic acid: C18:0
  • Eicosanoic acid: C20:0

Unsaturated Fatty Acids

  • Monounsaturated:
    • Palmitoleic acid: 16:1 (∆9)
    • Oleic acid: 18:1 (∆9)
  • Polyunsaturated:
    • Linoleic acid: 18:2 (∆9,12)
    • α-Linolenic acid: 18:3 (∆9,12,15)
    • Arachidonic acid: 20:4
    • Eicosapentaenoic acid: 20:5
    • Docosahexaenoic acid: 22:6

Structural Lipids

  • Glycerophospholipids
  • Plasmalogen
    • Up to 20% of human choline phospholipids are plasmalogens
    • Especially heart and nervous tissue

Fatty Esters of Glycerol (Triglycerides)

  • Three fatty acids with a single molecule of glycerol
  • They are nonpolar – hydrophobic
  • Serve as depots of metabolic fuel
  • Fat droplets in adipocytes (fat cells)
  • Stored in seeds
  • Lipase needed for mobilisation is also stored in these cells

Triacylglycerols

  • Can be simple or mixed
  • Tripalmitin, a simple triglyceride (3 x 16-carbon fatty acids)

Bilayer Permeability

  • Very low permeability for ions and most polar molecules
  • Water is an exception
    • Small size
    • High concentration
    • Lack of complete charge
  • Bilayer is permeable to other small molecules whose solubility in nonpolar solvents > that in water
  • Therefore, a need for transport proteins

Limitations of Simplified Membrane Descriptions

  • Simplified descriptions imply that there is only one membrane building block with this type of structure - the glycerophospholipid
  • Fluid mosaic model good
  • But diagrams often simplified and generalised
  • Descriptions often concentrate on plasma membranes of mammalian cells
    • Polar “head”
    • Non-polar “tail”

Membrane Structure

  • Key components:
    • Glycolipid
    • Oligosaccharide chains of glycoprotein
    • Lipid bilayer
    • Phospholipid polar heads
    • Sterol
    • Integral protein (single trans-membrane helix and multiple trans-membrane helices)
    • Peripheral protein (covalently linked to lipid)

Membrane Dynamics

  • Fluid Mosaic model
  • Lipids and many membrane proteins diffuse rapidly in the plane of the membrane (lateral movement)
  • BUT not transverse diffusion (flip-flop) through the membrane
  • Allows orientation, preservation of membrane asymmetry (e.g., phosphatidyl serine facing cytoplasm)
  • ATP dependent membrane enzymes (flippases, floppases ) maintain asymmetry

Flippases, Floppases, and Scramblases

  • Flippases and floppases move specific phospholipids against their concentration gradient using ATP
  • Scramblases are less specific, do not use ATP, and facilitate the movement of lipids down their concentration gradient

Membrane Fluidity

  • Membrane fluidity controlled by fatty acid composition and cholesterol content
  • Needs to be appropriate to the normal growth temperature of the organism

Mitochondria and Lipids

  • They synthesise lipids
  • Exchange them with other cell compartments
  • Membranes have a high content of phospholipids
  • Fewer sterols or sphingolipids than other cell membranes
  • Differences between inner and outer membranes
  • Inner mitochondrial membranes contain the most cardiolipin - it is synthesised there

Intracellular Signals - Phosphatidyl Inositol 4,5 Bisphosphate (PIP2)

  • Some hormones (e.g., beta-adrenergic agonists) bind to protein receptors on the plasma membrane and activate phospholipase C
  • This acts on (PIP2): phosphatidyl inositol, 4,5 bisphosphate
  • IP3 (inositol triphosphate) and DAG (diacyl glycerol) are released
  • IP3 acts on the ER to release Ca2+Ca^{2+} ions into the cytoplasm
  • DAG activates protein kinase C which phosphorylates other proteins

PIP2 Signaling

  • Was the first evidence of lipids as active participants in cell regulation
  • Process:
    • Phospholipase C acts on PIP2, creating DAG and IP3IP_3
    • IP3IP_3 triggers Ca2+Ca^{2+} release from the endoplasmic reticulum
    • DAG activates Protein Kinase C, leading to phosphorylation of substrates

Lipid Summary

  • Structure: Lipids are hydrophobic molecules composed mainly of carbon, hydrogen, and oxygen. They include triglycerides (fats and oils), phospholipids, and steroids. Phospholipids form the bilayer of cell membranes, while steroids like cholesterol provide membrane fluidity.
  • Energy Storage: Triglycerides serve as a major energy reserve in animals and plants, storing more energy per gram than carbohydrates due to their high-density hydrocarbon chains.
  • Insulation and Protection: Lipids provide thermal insulation in animals (e.g., adipose tissue) and act as a protective cushion around vital organs.
  • Biological Functions: Lipids play key roles in signalling (e.g., steroid hormones), waterproofing (e.g., waxes on plant leaves), and cellular communication (e.g., lipid rafts in membranes).

Carbohydrates: A Tale Behind the Name

  • Examples:
    • Glucose
    • Galactose
    • Mannose

Carbohydrate Structure

  • A hexose: 6 carbons
  • α form of glucose
  • A chair conformation of alpha-D (+) glucopyranose

Carbohydrate Definition/Formula

  • Carbohydrates: Carbon and Water
  • C<em>n(H</em>2O)nC<em>n(H</em>2O)_n
  • Example: C<em>6H</em>12O6C<em>6H</em>{12}O_6

Carbohydrate Groups

  • Monosaccharides (e.g., glucose)
  • Disaccharides
  • Polysaccharides

Monosaccharides

  • The simplest form (3-9 carbons)
  • Colourless, crystalline solids, soluble in water (-OH groups)
  • Single aldehyde or single ketone group

Disaccharides

  • Two monosaccharides
  • Formed by condensation reactions: removal of H2OH_2O.

Polysaccharides

  • Polymers of monosaccharides
  • Homopolysaccharides
  • Heteropolysaccharides
  • Formed by condensation reactions: removal of H2OH_2O.

Carbohydrates: Functions

  • Energy storage/supply
  • Structural functions
  • Signalling
    • Between cells
    • Within cells

Fischer Projections

  • Two-dimensional.
  • Linear.
  • Examples:
    • D-Ribose
    • 2-Deoxy-D-ribose

Ring (Cyclic Structure)

  • Interaction between free Alcoholic hydroxyls and Aldehyde or ketone groups
  • Aldehyde + Alcohol -> Hemiacetal
  • Ketone + Alcohol -> Hemiketal

Cyclic Structure Formation

  • Interaction between free Alcoholic hydroxyls (C5) and Aldehyde group (C-1) in D-Glucose.

Monosaccharide Groups (Prefix)

  • Ketone group: Keto…ose
  • Aldehyde group: Aldo…ose
  • Hydroxyl group
  • Dihydroxy: 2 hydroxyl groups

Monosaccharide Names: Carbon Numbers

  • Triose: Three carbon atoms
  • Tetrose: Four carbon atoms
  • Pentose: Five carbon atoms
  • Hexose: Six carbon atoms

Trioses

  • Glyceraldehyde (an aldotriose)
  • Dihydroxyacetone (a ketotriose)

Pentoses

  • D-Ribose (in RNA)
  • 2-Deoxy-D-ribose (in DNA)

Hexoses

  • Aldohexose: Glucose
  • Ketohexose: Fructose

Isomerism

  • Is atomic arrangements within the molecule that can significantly affect the function

Chiral Centres

  • Are carbon atoms that have four different chemical groups attached.
  • Not first or last C e.g. Aldohexoses contain four chiral centres (carbons 2,3,4,5).
  • Different arrangements of groups are possible at chiral centres making most carbohydrate molecules asymmetric/isomers.
  • Cannot be altered without breaking and making bonds.

Enantiomers

  • Where two molecules have the same functional groups but one is a mirror image of the other.
  • The two are not super-imposable.

Enantiomer Configurations

  • In a Fischer projection:
    • D configuration: if the OH group is to the right of the last chiral centre carbon.
    • L configuration: if the OH is to the left of the last chiral centre carbon.
    • Biological systems use almost entirely D sugars.

Enantiomers (Linear Forms)

  • Examples:
    • D-Glyceraldehyde v L-Glyceraldehyde
    • D-Glucose v L-Glucose

Enantiomers (Ring Forms)

  • D configuration: if the oxygen bond to the last chiral centre carbon is at the right.
  • L configuration: if the oxygen bond to the last chiral centre carbon is at the left.

Epimers

  • Occur where functional groups are arranged differently at one or more chiral centres
  • Not mirror images.
  • Refers to a one of stereoisomers

Epimers (Linear Forms)

  • Occur where functional groups are arranged differently at one or more chiral centres
  • All D

Epimers (Ring Forms)

  • Occur where functional groups are arranged differently at one or more chiral centres
  • All D

Polarised Light

  • Light is an electromagnetic wave
  • Unpolarised light oscillates at all angles
  • Planar polarised light oscillates in only one direction.
  • Chiral centres in dissolved molecules change this direction.

Optical Activity of Monosaccharides

  • Is the sum of activities of all the chiral centres in the molecule.
  • Some are dextrorotatory (rotate light clockwise) others laevorotatory (rotate light anti-clockwise).
  • DOES NOT totally correlate with D and L forms:
    • Dextrorotatory molecules are denoted (+) e.g., D (+) glucose.
    • Does not have wide biological significance.

Anomers: Only for Rings

  • Anomeric carbons = ones involved in hemiacetal or hemiketal bonding during ring formation

Anomers: α and β

  • α- and β- anomers for hexoses
  • α = carbon 6 and new hydroxyl group on opposite sides of ring
  • β = groups on the same side of ring

Glucose Anomers

  • α-D-glucose
  • β-D-glucose

Pyranoses and Furanoses

  • Furan = “Five in the ring”
  • Pyran = “Six in the ring”
  • Aldohexoses predominantly pyranose (C1-C5/OH)
  • Ketohexoses predominantly furanose (C2-C5/OH)

Conformers: Only for Rings

  • Pyranose rings are not flat because of C bond angles
  • Strain causes puckered conformations
  • Rings flip between these
  • “Boat” and 2 types of “chair” most famous

Monosaccharide/Isomers - Summary

  • Molecules with the same composition but different characteristics
  • Important carbons:
    • Chiral centres (all carbons except the first and last)
    • Anomeric carbons (carbons only involved in ring formation)
  • Fischer projections and rings:
    • Enantiomers: mirror images of each other (L and D)
    • Epimers: different configuration
    • Optical isomers (+ and -)
  • Rings (cyclic structure):
    • Anomers: different configuration at the hemiacetal or hemiketal carbon atom (anomeric carbon). Alpha, beta
    • Pyranoses and furanoses: Furanose, Pyranose
    • Conformers: boat, chair, half chair