Problem Set 6: L11-12
Which of these fatty acids would have a higher melting point, 18:3 or 24:0? Why?
24:0 would have a higher melting point because it is both longer and more saturated than 18:3. Longer fatty acids have higher melting points because there are more intermolecular interactions between chains for longer chains. Saturated fatty acids have higher melting points because the chains are linear and able to pack together tightly.
For a monosaccharide with n chiral centers, how many possible stereoisomers are there?
2^n stereoisomers.
What is the catalytic activity of a flippase, versus a floppase, versus a scramblase?
A flippase specifically moves PE and PS from the outer leaflet to the cytosolic (inner) leaflet, a floppase moves phospholipids in the opposite direction (from inner cytosolic to outer leaflet). A scramblase can move lipids either way depending upon the diffusion equilibrium. These are required because otherwise movement of lipids from one leaflet of the bilayer to the other is very, very slow.
How do agarose polysaccharide chains organize to form gels?
Agarose chains are heteropolysaccharides of D-galactose linked through a beta 1-4 linkage to 3,6-anhydrogalactose, with some of the 3,6-anhydrogalactose modified with sulfate or pyruvate groups. Two agarose chains form a double helix with one another, and the double helices aggregate and crosslink together into filaments. A larger superstructure with pores assembles out of the filaments and water becomes trapped in the central cavities of the helical structure to form the gel.
How does cyclization differ for aldoses versus ketoses?
Aldoses form a hemiacetal, pyranose ring, whereas ketoses from a hemiketal, furanose ring.
What is the structural difference between a cerebroside, a globoside and a ganglioside? Which one contains sialic acid? What is the difference between a GM ganglioside and GT ganglioside?
All three of these lipids are made using a sphingosine backbone. Cerebrosides are sphingolipids with a single sugar head group, globosides have multiple sugars, and gangliosides have multiple sugars including at least one sialic acid. Cerebroside and globoside head groups are neutral, whereas ganglioside head groups are charged. Gangliosides are classified by the number of sialic acid residues their head group contains. A GM ganglioside has a single sialic acid, GT has three sialic acids in the head group.
Compare and contrast the structure of sphingomyelins with glycerophopholipids.
Although they are composed of different backbones (sphingosine versus glycerol-3-phosphate), the structure and properties of sphingomyelins is quite similar to glycerophospholipids. Both have two acyl tails and polar head groups, and their geometry is similar. Both sphingomyelins and glycerophospholipids have phosphorylated head groups such as phosphocholine or phosphoethanolamine and so are also phospholipids. They differ in that sphingomyelin has one tail already attached to the backbone, and the remaining tail is attached through an amide linkage rather than the ester linkage used to attach both acyl tails in phosphoglycerolipids. Additionally, the headgroup for phosphoglycerolipids is attached to C3, whereas in sphingomyelins it is attached to C1.
What sugar is commonly found in the L form?
Arabinose.
How does the structure of Archaea membrane lipids facilitate their extremophile lifestyle?
Archaea use glycerol dialkylglycerol tetraethers as their membrane lipids. These are based on two glycerol backbones attached to both ends of the fatty acid chains through ether linkages. They differ chemically from glycerophospholipids in three primary ways (1) the fatty acid chains average about double the length, (2) there are polar head groups at both ends, (3) the fatty acids are linked by ether linkages, whereas most glycerophospholipids are attached by ester linkages. The structural result of these differences is that glycerol dialkylglycerol tetraethers don't need to form a bilayer to make a membrane. Functionally because the membrane is not a bilayer and because of the ether linkages, glycerol dialkylglycerol tetraether membranes are more stable at high temperatures and resistant to oxidation, alkaline degradation and high salt concentrations. This allows Archaea to tolerate more extreme environments than other organisms.
Which interaction is predominant in the guiding of polysaccharide folding into tertiary structures and why?
Because of the high density of hydroxyl groups on polysaccharides, hydrogen bonding is the most predominant interaction that guides tertiary structure.
What structural characteristics do starch and glycogen have in common?
Both starch and glycogen are made of chains of alpha-amylose. Alpha amylose is a homopolysaccharide composed of α-D-glucopyranose residues linked by alpha 1-4 bonds. Both glycogen and starch are branched, with branch chains linked by alpha 1-6 linkages to the original chain. Both starch and glycogen are sugar storage molecules, with individual residues released through enzymatic cleavage from the ends of the chain when needed.
Describe the structure of cellulose and explain why it has such great tensile strength.
Cellulose is a homopolysaccharide composed of D-glucopyranose units linked in a very tight beta 1-4 conformation. This forms rigid linear chains that bundle together in parallel as microfibrils to form a larger cellulose fiber. Each cellulose chain is hydrogen bonded extensively to itself and the proximal chains. The extensive hydrogen bonding and bundled structure results in the great tensile strength of cellulose.
What are two monosaccharides that are epimers of D-glucose? How do they differ?
D-Mannose is an epimer of D-glucose that differs at C-2. D-Galactose is an epimer that differs at C-4.
What is an epimer?
Epimers are two sugars that differ only in their chiral configuration of the alcohol around a single carbon in the backbone.
How do galactolipids, sulfolipids and glycerophospholipids differ structurally from one another? Which class is critical for photosynthesis?
Galactolipids, sulfolipids anf glycerophospholipids all are build on a glycerol backbone. However, glyceropphospholipids have phosphorylated head groups, while galactolipids and sulfolipids have sugar head groups (generally galactose) instead. For sulfolipids the sugar head groups are sulfated, giving them a negative charge. Galactolipids such as MGDG and DGDG are critical for photosynthesis.
What structural characteristics are different between starch and glycogen?
Glycogen has a more densely branched structure, with branch points occurring every 8-12 residues. Starch has a more loosely branched structure with alpha 1-6 linkage points every 24-30 residues.
Describe the disaccharide repeats that are typical of glycosaminoglycans.
Glycosaminoglycans are made from alternating repeats of disaccharides composed of an acidic sugar residue (D-gluronic acid L-iduronic acid) and an amino sugar residue (D-galactosamine or D- glucosamine). The amino sugars are usually sulfated.
How does the structure of glycosaminoglycans contribute to their function in joints?
Glycosaminoglycans have a high density of negatively charged groups due to the sulfation of the amino sugars and carboxylic acid groups on the acidic sugars. The negatively charged groups generate repulsive forces that cause GAGs to form an extended rigid rod-like conformation to minimize the repulsive forces. When brought together, GAG chains "slip" past each other due to the repulsion of their negative charges. This produces the "slippery" consistency of mucous secretions and synovial fluid. When GAGs are compressed in a joint, water is squeezed out and the GAGs are forced to occupy a smaller volume. When compression of the joint is released, GAGs spring back to their original (hydrated) volume due to repulsion of their negative charges.
Briefly explain what hop diffusion is and what this tells us about membrane organization.
Hop diffusion describes the motion of a lipid within the same leaf of a bilayer. Lipids move through random diffusion, but are generally constrained to a specific sector of the membrane. Occasionally the lipids will "hop" to a new sector, and then diffuse randomly within that sector until hopping to another one. These patterns of movement indicate that membrane organization is not homogenous, but instead ordered into different microdomains.
Which interactions guide polysaccharide folding into tertiary structures?
Hydrogen bonds, hydrophobic interactions and van der Waals interactions all promote folding of carbohydrate chains. For polysaccharide chains with charged side chains, electrostatic interactions also contribute.
If you analyzed the lipid content of a human tissue sample & found that the glycerophopholipids were enriched in ether linked acyl chains, which tissue would you expect your sample was from?
I would expect this sample was likely to be from heart tissue because ether linkages are rare in glycerophospholipids, except for heart tissue. Around 50% of cardiolipids have ether linked acyl chains.
What is the difference between a lipid bilayer in a liquid-ordered state and a liquid disordered state? What state are membranes in our body?
In the liquid-ordered state, motion of individual lipid molecules is highly constrained. In the disordered state, there is a high degree of lateral and rotational motion for each lipid molecule. Membranes in our body exist between these states in what is called a "gel phase," which is organized but still highly dynamic.
How does the structure of sterol differ from other structural lipids that are found in membranes?
Instead of having two fatty acid tails like other structural lipids, sterols have a rigid four ring structure that is planar and bulky with a short lipid tail attached. Sterols don't have large polar head groups like other lipids, although they may have a small polar group (i.e. cholesterol hydroxyl group) attached to the planar ring system.
How do lipid rafts facilitate signaling? How does their lipid content contribute to the structure and function of these rafts?
Lipid rafts are structurally ordered microdomains that facilitate signaling by bringing related proteins into proximity. A single microdomain might assemble so that a receptor protein and signaling protein that need to interact are spatially concentrated together. This localized enrichment can facilitate interaction and activation of protein signaling complexes. Lipid rafts are more ordered than the surrounding membrane because they are enriched in cholesterol and sphingolipids which interact together to form a thicker, more rigid domain.
Why do some lipids form micelles and other lipids form bilayers/vesicles?
Lipids with a single fatty acid tail are conical in shape because the head group has a wider diameter than the tail. Lipids with two fatty acid tails are cylindrical in shape because the head group and tail have approximately the same diameter. Conical lipids pack into a micelle shape like slices of a pie, cylindrical lipids pack in parallel to make bilayers (that then curve into vesicles).
How do monosaccharides cyclize?
Monosaccharides cyclize when the carbonyl group forms a covalent bond with the oxygen of a hydroxyl group elsewhere on the sugar chain through a condensation reaction.
What is the mechanism of action for penicillin and other beta lactam antibiotics that disrupt bacterial cell wall biosynthesis?
Penicillin and other beta lactams are substrate mimics of the acyl-D-Ala-D-Ala substrate peptide from peptidoglycan NAM residues that transpeptidase links to other NAM-linked peptides to crosslink the polysaccharide chains into a sheet structure that makes up the cell wall. These mimics stick in the active site but can't be acted upon, and thereby act as suicide inhibitors of transpeptidase to disrupt cell wall biosynthesis.
Describe the structure of peptidoglycan. What crosslinks the polysaccharide chains together?
Peptidoglycan is a heteropolysaccharide composed of N-acetylglucosamine (NAG) linked by beta 1-4 linkages to N-acetylmuramic acid (NAM). Each NAM residue is modified with a short peptide chain connected to the C-3 lactic acid group. The polysaccharide chains are arranged in parallel chains with peptide bonds occurring between each NAM peptide side group to link the chains together into a sheet that together into a very strong cell wall.
What is the structural difference between phosphatidic acid and phosphatidylserine?
Phosphatidic acid is a phosphoglycerolipid with a single hydrogen atom attached to the phosphate as the R group. Phosphatidylserine has a serine residue as the R group attached to the phosphate.
Which type of lipids are more often found in the outer monolayer of the plasma membrane?
Phosphatidylcholine and sphingomyelin are present in higher levels in the outer leaf of the lipid bilayer than in the inner leaf.
What is sphingosine? For lipids with a sphingosine backbone, to what carbons are the other functional groups attached? How many acyl tails attach to sphingosine to make a sphingolipid?
Sphingosine is an amino alcohol with a long-chain fatty acid tail. The head group attaches to C1 on sphingosine, the fatty acid tail attaches to C2 and the sphingosine tail remains attached to C3. Only one other acyl tail attached to sphingosine to make a sphingolipid.
You are trying to identify microbes that are more tolerant of cold climates. You analyze the lipids of strain 1 and find that it has 3 times the amount of unsaturated lipids as strain 2. Which strain would you expect to be more tolerant of cold environments? Why?
Strain 1 would be more tolerant of cold environments because the increased levels of unsaturated lipids in its membranes would yield increased fluidity due to their bent acyl tail conformations that disrupt the crystalline packing of the surrounding linear acyl tails.
Why are sugars stored as polymers in cells?
Sugars are stored as polymers to avoid disturbing the osmotic potential of the cell.
Explain the structural difference between O antigen, A antigen and B antigen that determine blood type in the ABO system.
The ABO system is based on the patterns of sugar residues on globoside lipids in our blood cell membranes. People with O antigen have a pentamer sugar headgroup; those with A antigen have an additional N-acteylgalactosamine residue added to the end of the pentamer while those with B antigen have an additional galactose instead of N-acetylgalactosamine.
What is the functional role of branching in starch and glycogen?
The branching generates more ends, so many sugar residues can be released at the same time through enzymes acting on the end of each branch.
How can you tell that a carbohydrate is the D stereoisomer.
The hydroxyl group on the chiral carbon farthest from the carbonyl position is positioned to the right.
How many carbons are in the glycerol backbone region of glycerophospholipids? What kind of linkages attach the head groups and acyl tails, and which carbons of the glycerol backbone do they attach to?
There are three carbons in the glycerol backbone, the acyl tails are attached to carbon 1 and 2 by an ester linkage (and in rare cases by an ether linkage) and the head groups are attached through a phosphodiester bond to carbon 3 (except for phosphatidic acid which only has a hydrogen as the head R group).
