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Define lipid molecule
Molecule that does not dissolve or solubilize in aqueous environment
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5 characteristics of fatty acid molecule
- Long hydrocarbon chain
- Carboxylic acid group on one end
- Can be amphipathic
- Majority hydrophobic
- Essentially can have TWO types of fatty acids (saturated and unsaturated)
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Define saturated and unsaturated
What does it mean to be more or less saturated, with regard to comparing lipid saturation or unsaturation?
- Saturated: maximum number of hydrogens, only single bonds
- Unsaturated: one or more double bonds (can be cis or trans)
- LEAST saturated: MOST # of double bonds
- MOST saturated: LEAST # of double bonds
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Saturated fatty acids have only ______ bonds, with carbons numbered from the _______ _____ end.
- single bonds
- carboxylic acid end
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What would be the systematic name and Numeric symbolism of a 16 carbon carboxylic acid?
- Systematic name: Hexadecanoic acid (Palmitic acid)
- Numeric symbolism: 16:0 (meaning: 16 carbons: 0 double bonds)
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Systematically name the SATURATED fatty acids with the following # of carbons:
12
14
16
18
20
22
24
26
28
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Guidelines on how to systematically name an unsaturated fatty acid (7-story)
- 1. First, determine the position and the # of cis and or trans double bonds
- 2. Second, in the very front, write cis and or trans with a Δ superscript and the carbon positions of the double bonds
- 3. Third, use one of the four prefixes (do-, tetra-, hexa- or octa-) and place it after the cis/trans. This is part of normal naming and it is meant to provide the exact number of carbons.
- 4. Then write the remaining name using the word deca or cosa.
- 5. Then insert another word from (di, tri, tetra, penta, hexa) to indicate the number of double bonds in the fatty acid. Please note if there is just ONE double bond in the fatty acid, we do NOT use mono. It is understood that there is ONLY one double bond.
- 6. Then insert the letter "e".
- 7. Follow this by the word "-noic;" leave a space and LASTLY, the word acid.
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Draw cis double bonds and trans double bonds
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Name the following carboxylic acids, state their numerical symbolism and name from the ω end:
- Systematic name: cisΔ9 Octadecenoic acid (oleic acid)
- Numerical symbolism: 18:1 (18 carbons, 1 double bond)
- Naming from the ω end: ω-9-octadecenoic acid
- Systematic name: CisΔ13,16 docosadienoic acid
- Numerical symbolism: 22:2
- ω name: ω-6-docosadienoic acid
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What is the name of the systematic and common name of the fatty acid structure? Use ω and non-ω methods and provide a numerical symbolism
- Arachidonic acid (common)
- cisΔ5,8,11,14 Eicosatetraenoic acid
- ω-6-eicosatetraenoic acid
- 20:4
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- CisΔ9,15 transΔ11,13 octadecatetraenoic acid
- ω-3-octadecatetraenoic acid
- 18:4
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Please provide a systematic name for this fatty acid and numerical symbolism:
- transΔ11octadecenoic acid
- 18:1
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Consider the following fatty acids:
Hexadecanoic acid, cisΔ9,12 hexadecadienoic acidΔ7,10,13 hexadecatrienoicacid. Which fatty acid is considered to be the most unsaturated?
Which fatty acid acid is considered to be the most saturated?
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Use the structure of glycerol to display the storage of fats as triacylglycerols
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Imagine that we have two fatty acid molecules both containing 18 carbons: cisΔ9,12octadecadienoic acid and cisΔ9,12,15octadecatrienoic acid
Which will have a higher melting point (MP)?
What is the general rule?
- One with only two double bonds
- More intermolecular forces (IMFs) between molecules
- Thus, more energy needed to break IMFs
- The type of IMF present is known as the London dispersion force
- Results in instantaneous dipoles
A general rule: the GREATER the # of double bonds, the more kinks present, the LESS stable formation of IMF, resulting in a lower melting point
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Phospholipids are part of the ______ ______. Essentially, there are two types of phospholipids, _________ and ________. What is the significance of R1, R2 and X?
- cell membrane
- phosphoglycerides and sphingolipids
- R1 and R2 = fatty acid molecules
- X = site of an alcohol group attachment
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What are the working parts of a membrane phospholipid (glycerophospholipid)?
- A glycerol molecule
- 2 Fatty Acid molecules
- A phosphate
- A site for alcohol group-containing compound attachment
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Depict a breakdown of storage and membrane lipids and what they bind
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How are phospholipids built? In other words, what is the backbone?
By design, memrane lipids are _______. Why is this so important?
How do we differentiate phosphoglycerides?
- Through their glycerol backbone
- Amphipathic
- Necessary to contact aqueous parts of the cell
- Through the attachment of different -OH containing groups
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Name that phospholipid:
Phosphatidylcholine
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Name that phospholipid:
Phosphatidylinositol
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Name that phospholipid:
Phosphatidylserine
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Name that phospholipid:
Also keep in mind the double bond cut off at the bottom is attached to an oxygen. What is the significance of these red circled regions?
- Phosphatidylethanolamine
- The red circled regions are the hydrophilic regions that appear on the outside of the cell (facing the extracellular matrix) or the intracellular side (facing the cytoplasm)
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What do you call a phospholipid with a sugar present?
glycoplipid
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Name that phospholipid:
A Sphingolipid or Sphingosine
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Given these formulas for X, state the name of the sphingolipid and Name the X-O linkage
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What principal molecules make up a membrane? (Can apply to prokaryotic as well as eukaryotic)
- Lipids (specifically-phospholipids and sphingolipids)
- Proteins (receptors, transport proteins, channels)
- Cholesterol
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Give examples of the molecules described and state the direction of permeability. List from least to most permeable
 - Charged molecules (amino acids) < ions < uncharged molecules (glucose) < Small molecules (water) < Gases
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Cholesterol is typified by ______ ______ ______ structure. It is the predominant component of _______ cell membranes and is highly enriched in _______ cell membrane (___% composition). It reduces _______ at moderate temperatures (due to cholesterol's rigid shape), and preventing ________ at low temp.
- 4 fused ring structure
- animal cell membranes
- nerve cell membrane
- (~25% composition)
- fluidity (due to their rigid shape)
- solidification at low temp.
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How do unsaturated tails affect the structure of the phospholipid bilayer as opposed to saturated tails?
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What role does cholesterol play in the phospholipid bilayer
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In a Biphasic membrane melting curve charting fluidity (y) against temperature (x), what does a sigmoidal curve suggest as opposed to a straight line?
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Name that molecule:
Cholesterol
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Enzymatic modulation of face-specific lipid abundance builds and regulates ______ ______
membrane asymmetry
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What are Flippase, Floppase, and scramblase? Flippase and floppase are ______ meaning they use _____ ______ to function
- membrane-spanning enzymes that function to rearrange phospholipids in cell membrane
- ATPase
- ATP hydrolysis
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State the specific functions of:
Flippase
Floppase
Scramblase
explain all abbreviations
- Flippase: moves PS, PE, and PI from extracellular side to intracellular side
- Floppase: moves PC and SL from intracellular side towards extracellular side
- Scramblase: moves lipids both ways (in-to-out and out-to-in) specifically, relocates PS from in-to-out during apoptosis
LIPID KEY
- PS = phosphatidylserine
- PE = phosphatidylethanolamine
- PI = phosphatidylinositol
- PC = phosphatidylcholine
- SL = sphingolipid
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Of these phospholipids, which are expected to be on the extracellular side and which is expected to be on the intracellular (cytoplasmic) side:
PS = phosphatidylserine
PE = phosphatidylethanolamine
PI = phosphatidylinositol
PC = phosphatidylcholine
SL = sphingolipid
What is the significance of the phosphatidylserine rearrangement to extracellular matrix?
- PC and SM - high extracellular side
- PI, PS and PE-high intracellular side
Significance: Movement of PS from inner to outer side during apoptosis, serves to enhance apoptosis signal
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Why have cells evolved lipid rearranging/flipping enzymes? (3-story)
The lateral versus transverse diffusion challenge
- Lipids can move laterally at a rate of 106 per second
- However, the rate of spontaneous flip-flops (transverse diffusion) is SLOW ~105 seconds (= ~1 DAY!!)
- Enzymes (flippase, floppase, and scramblase) considerably reduce rate to mere seconds
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A ________ plot is an experimental method that pertains to membrane proteins, what its function?
A hydropathy plot: usefule for determining transmembrane spanning segments
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In addition to liids, proteins also present in the ______ and ______ of the membrane. Name two classes of membrane proteins (explain each)
- membrane and surface of the membrane
- Integral: span membrane, hydrophobic α-helical structure but also β-strand structure
- Peripheral membrane protein: covalently attached through PTM using lipid anchor
*Can be present inside or outside of the cell
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What is the significance of the X and Y axis of a hydropathy plot? According to the plot, what are the expected values for hydrophobic and hydrophilic residues?
- Y-axis: hydropathy index value or hydrophobicity (There are other scales)
- X-axis: amino acid (or residue) number #
- Hydrophobic residues: > 0 to ~+4.5
- Hydrophilic resiudes: < 0 to ~-4.5
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What is the likely functional significance of proline residues that occur at the end of α-helices?
- Break intrahelical hydrogen bonds by introducing kinks
- This enables helix destabilization and hence breaks the helix
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The entire sequence is taken from a membrane protein. The underlined sequence forms a transmembrane-spanning α-helix. The proline residue towards the end of the sequence is at position 356. Which residue does it break a hydrogen bond with? (Provide the residue # and please clearly circle the residue)
WVAEIGLAFNILGMVVFAFATITPL...
- Alanine 352, it is colored in red here.
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Proline position mapping example problems
Predicting proline-deppendent intrahelical hydrogen bonding network breaks
Example:
Imagine that a protein has a proline residue at position 335. Which residue does it not donate a hydrogen bond to?
331
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Imagine that a residue at position #50 is unable to make a hydrogen bond with a proline. What is the residue number of the proline?
54
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Estimating α-helical length from actual α-helices. To recap, what have we learned so far (in previous module) regarding α-helices? From an actual model, we learned to determine the # of residues as well as the # of intrahelical hydrogen bonds
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Here, we will take it a step further and determine helical length using the helical rise parameter: Determine the length of this transmembrane-spanning alpha helix, there are 9 turns.
9 turns * 3.6 residues/1turn * 1.5Ä rise (angstroms)/1 residue = 49Ä
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When analyzing a stretch of a given protein sequences to determine if it can likely form into a transmembrane-spanning α-helix, what are two crucial determining factors?
Length and hydrophobicity
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Based on your knowledge on the prediction of transmembrane α-helical segments, would you predict that the sequence above can form a transmembrane α-helix? Please explain your reasoning. Do a helical length determination
H3N+1...LVMLSYGLGMAVTIAAVFKMG...COO-1
- Count the number of residues (should be around at least 18-19 residues)
- The helix is 21 residues, so number of residues qualifies for being a transmembrane helix candidate
- Determine % hydrophicic (GAV LIM FWP) residues (should be at least ~70%)
- This helix has 17 hydrophobic residues out of a total of 21 residues, so it is ~82% hydrophobic
- ~1.50 Ä is a helical rise parameter. The helical length can be approximated as a product of the helical rise times the number of amino acids residues 1.50Ä x 21 residues = 31.5Ä (minimum transmembrane helix length is ~28-30Ä)
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