Lecture 5: Sugars & Carbohydrates/Lecture 6: Lipids, Membranes, and Solute Transport Flashcards
Which C attacks the aldehyde in glucose to form a ring?
C5
Describe the composition of amylose
Unbranched and composed of α-1,4 glycosidic bonds
How are lectins and carbohydrates bound? What does this allow for?
By a number of weak non-covalent contacts that ensure specificity yet permit unlinking, as needed
Are lipids water soluble?
No
What is an amphiphatic molecule?
Molecules that contain hydrophobic and hydrophilic moeities
How are proteins/enzymes marked to be directed to the lysosome to function there? Which enzyme does this?
With mannose-6-phosphateGlcNac phosphotransferase adds M6P
What are oligosaccharides?
Linked monosaccharides
Describe cholesterol’s composition and what it means for the bilayer (3 parts)
- Flexible alkyl side chain
- Steroid nucleus made from linked hydrocarbon planar rigid rings
- Head: hydroxyl group interacting with other lipid head groups –> its interaction with other lipids affects bilayer fluidity
How mobile are lipids compared to proteins?
More mobile
What are the 3 forms of glucose composites?
Glycogen (animals), starch (plants), and cellulose (plants)
Describe the composition and branching of glycogen
Composed of α-1,4 glycosidic bonds, with α-1,6 glycosidic branches every 8-12 glucose molecules
How do proteins that are integral part of the membrane interact extensively with the hydrocarbon region?
Alpha helices or beta sheets with turns and loops interacting with polar head groups
Describe lipid bilayer formation
Spontaneous self-assembly process in which hydrophobic interaction are a major driving force
What will be the effect on the melting point of a lipid to add more unsaturated fatty acids?
Decrease its melting point → due to the kinks in the unsaturated fatty acid, the molecules won’t pack as closely and so will have fewer intermolecular forcesIf there is a kink: melting point decreases!
Which C attacks the aldehyde in fructose to form a ring? 2 options: which one is most common?
C5 (more common) or C6
Which is the preferred conformation and why: llipid bilayer or micelle?
Bimolecular lipid bilayer sheet, since many lipid hydrocarbon tails are too long to favorably fit in a micelle
What are lectins? What are they important for and how?
Receptors (proteins) that bind the carbohydrate moeity (eg: M6P) Very important in mediating cell-to-cell contacts: most lectins contain 1-2 carbohydrate binding sites, allowing a cell to bind to its neighboring cell’s sugar-covered surface.
Effects of cholesterol on fluidity of plasma membrane?
Overall: moderating effect on membrane fluidity: given cholesterol’s rigid structure, it reduces the fluidity of membranes, to an extent. However, since cholesterol prevents the hydrocarbon chains from interacting one another, it makes it harder for the bilayer to lose all fluidity. At physio temperatures: increasing cholesterol content would decrease fluidityAt cold temperatures: increasing cholesterol would increase fluidity because it keeps the phospholipids from clumping together
What are the 2 types of cyclic sugars? Which one is most common and why?
Alpha (OH on bottom) or beta (OH on top)
Beta is more common (65%) because less steric hindrance between C1 and C2
What are the 4 biological roles of lipids?
- Fuel
- Energy storage
- Signaling
- Membrane components
What types of lipid characteristics would you aim for/use, to ensure that when in solution, most of your lipids will self-assemble into micelles versus lipid bilayers, and why?
Short and small tails would work better for micelles. More space constraints otherwise.
What is a 6 C sugar ring called?
Pyranose
What are the 2 types of phospholipids and their differences?
- Glycerophospholipid: glycerol backbone and fatty acids attached by ester bonds
- Sphingolipid: sphingosine backbone and fatty acids attached by amide bonds
What are the 3 main components of a lipid?
- Fatty acid chains
- Backbone (often glycerol)
- Hydrophilic components
What are fatty acids?
Long hydrocarbon chains of various length and saturation terminated with a carboxylic acid
What is a monosaccharide with 3 carbons called?
Triose
How does lysosomal hydrolase work?
When you make it it’s in inactive form in the ER (so it’s not chopping up proteins like cray) –> precursor will get modified with a sugar (M6P) –> the precursor goes in lysosome –> low pH will make it active and it will loose the M6P complex
What is the empirical formula for carbohydrates?
(CH2O)n
What are lipids soluble in?
Organic solvents
What is a monosaccharide with 7 carbons called?
Heptose
Describe the composition of cellulose.
Composed of β-1,4 linkages, forming long, strong, straight, unbranched chains. The chains H-bond with another, generating a rigid, supportive structure for structural support
Why is it necessary to store glucose?
High concentrations of free glucose can disturb the osmotic balance of a cell: the compact structure does not allow water to interact with the interior, and therefore will not enter the cell. If it did, the water would rush in causing cell lysis
What is a monosaccharide with 4 carbons called?
Tetrose
What is a 5 C sugar ring called?
Furanose
What are the 2 types of monosaccharides?
Ketose or aldose
What is the difference between amylose and cellulose in plants?
Amylose is for glucose storage vs cellulose is for structural support
How do you name a glycosidic bond?
alpha/beta-C#-C#-glycosidic bond
What will be the effect on the of a lipid bilayer to add more saturated fatty acids?
Decrease the fluidity of a cellular lipid bilayer because the phospholipids will pack closely → lead to a more rigid lipid leaflet, as their straight hydrocarbon chains interact favorably with one another
Which C is C1 for ketoses?
The C before the C=O
What is a monosaccharide with 6 carbons called?
Hexose
What are the 3 common types of membrane lipids?
- Phospholipids
- Glycolipids
- Cholesterol
What is a glycolipid? What are the 2 types of glycolipids? What bond attaches the fatty acid? What bond attaches the sugar? Where does the sugar group extend?
Sphingosine or glycerol backbone + fatty acid(s) attached by amide bond + sugar attached by ester bond and extends from the lipid bilayer
2 types: sphingolipids or galactolipids (sulfolipids)
What will be the effect on the fluidity of a lipid bilayer to add more unsaturated fatty acids?
Increase the fluidity of a cellular lipid bilayer because the phospholipids will not pack as closely –> they are kinked or bent, thus interfering with the tight packing of hydrocarbon tails and will decrease the overall potential hydrophobic interactions
What is the lectin involved in transport to the lysosome?
The Golgi lectcin M6P receptor
What is a hemiketal? What is the formula?
A ketone attacked by an alcohol: HO-C-OR
What are the 2 conformations a pyranose can adopt? Which one predominates? Why?
Chair or boat
Chair predominates because all of the axial positions are occupied by H atoms with the bulkier OH and CH2OH in equatorial positions
What is the average rate at which a lipid diffuses?
1um/s
What is sucrose and what is it cleaved by?
Alpha D glucose + beta D fructose (with alpha glycosidic bond)
Cleaved by sucrase
What is a monosaccharide with 5 carbons called?
Pentose
In what form do many common sugars exist in? Why?
Cyclic form because the second to last OH attacks the aldehyde or the ketone
What is lactose and what is it cleaved by?
Beta-D-galactose + alpha-D-glucose (with beta glycosidic bond)
Cleaved by lactase
What are epimers?
Isomers who differ only at 1 C
What is a hemiacetal? What is the formula?
An aldehyde attacked by an alcohol: HO-C-OR
Give two examples of epimers? At what C do they differ?
- D-glucose and D-mannose (C-2)
2. D-glucose and D-galactose (C-4)
What is the main reason why lipids form membranes?
The amphiphatic nature of lipids led them to form micelles or lipid bilayers: their polar headgroups favor interaction with water, while their hydrophobic tails prefer interaction with another over water.
From linear to cyclic: how do I know if the OH is up or down?
OH on the right –> OH down
OH on the left –> OH up
What is maltose?
Disaccharide composed of 2 α-D-glucoses (alpha glycosidic bond)
Which C is C1 in aldoses?
The aldehyde
What is super special about carbs?
Most abundant bio molecules on Earth
Which ones have more monosaccharides: oligo or poly-saccharides?
Poly
What are glycoconjugates?
Carbohydrates covalently attached to proteins or lipids
How many Cs to monosaccharides have?
3-7
What is the anomeric C?
The new chiral C formed by the formation of the sugar ring structure
What is another name for glucose?
Dextrose
Why do hemiacetals/hemiketals form?
Because the carbonyl C is a good electrophile and the O in OH is a good Nu
What can further happen to hemiacetals/hemiketals?
Attacked by O again to form acetals/ketals
In real life, what percentage of D-glucose is in open-chain form?
1%
What is super special about glucose?
Every organism uses it as fuel
What are 2 examples of ways in which sugars can be modified?
Exchange one of the OH groups with sulfonate or amino groups
What is an aldonic acid?
Sugar acid obtained by oxidation of the aldehyde functional group of an aldose to form a carboxylic acid functional group.
What is an uronic acid?
Sugar acid obtained by oxidation of the terminal CH2OH functional group of an aldose to form a carboxylic acid functional group.
What is the reducing end of an oligosaccharide?
The monosaccharide unit with a free anomeric C
What are the non-reducing end(s) of an oligosaccharide?
All terminal units in which the anomeric C is part of a glycosidic bond
What is necessary for a sugar to be a reducing agent?
Needs to be in open-chain form
What are the 2 trioses?
dihydroxyacetone and d- and L-glyceraldehyde.
What are the 3 characteristics of monosaccharides to classify/name them?
- Placement of carbonyl group
- Number of Cs
- Chirality
How to calculate number of stereoisomers?
2^(# of chiral centers)
What are D/L configurations based off of? Which one is more common in biology?
On the absolute configuration around the carbon atom farthest from the carbonyl carbon relative to that of the simplest carbohydrate, glyceraldehyde
D is much more common in bio
What is an exception of D sugars being the most abundant in nature?
L-arabinose
What are the 2 ways of fixing the sugar ring in either alpha or beta at the anomeric C?
- Substituting the OH with anything other than H
2. Glycosidic bond
What can confer a negative charge to a sugar?
Carboxylation or sulfation
How many reducing ends can a reducing sugar have?
1!
How does the reducing end of a sugar help to name it?
Disaccharides are commonly named from their non-reducing to their reducing end
Can disaccharides be absorbed directly by the intestine?
No
What happens if enzymes such as lactase or sucrase are lacking?
The sugars lead to fermentation in the bowel as they are metabolized by gut bacteria, resulting in symptoms of intolerance such as lactose intolerance
What is another word for polysaccharides?
Glycans
What are the 3 main functions of polysaccharides?
- Fuel
- Structure
- Information transfer
What are the 2 characteristics of polysaccharides to classify them?
- Homo/Hetero
2. Branched/Unbranched
What is the similarity and the difference between starch and glycogen?
Humans can utilize either starch or glycogen as a fuel source, but we only synthesize glycogen
How is glucose released from glycogen?
One at a time from the non-reducing end
What is the milieu interieur/extra cellular matrix composed of?
Glycosaminoglycans: long polymers of repeating disaccharide units, often heavily sulfated and negatively charged.
What is hyaluronic acid=hyaluronate? What is its purpose?
A glycosaminoglycan composed of 50,000 repeating units of d-glucuronic acid and N-acetyl glucosamine with a ß1—>3 linkage. Hyaluronic acid forms highly viscous fluids and serves as a lubricant in the synovial fluid of joints and vitreous humor of the eye
What is heparin? Describe its composition
Fractionated form of heparin sulfate (attached to proteoglycans): 15-90 repeating paris of GlcA25 or IdoA25 linked at alpha 1–>4 with GlcNS3S6S
that inhibits thrombin by increasing its affinity w/ its inhibitor
What is the purpose of the sugar code?
Carbohydrates are covalently attached to proteins (glycoproteins) and lipids (glycolipids), and these sugar moieties are the face that each cell presents to the world
What do lectins do?
They recognize carbohydrate structures
What are selectins?
Family of cell-surface lectins that mediate cell-cell recognition and adhesion
Why are human selectins important?
They mediate the inflammatory responses in rheumatoid arthritis, asthma, psoriasis, multiple sclerosis and the rejection of transplanted organs (e.g. they allow T lymphocytes to attach to the capillary endothlium during inflammations), and are of great interest as the targets of drugs that can inhibit their interaction with the carbohydrates they recognize
What is the role of sialic acid on glycoconjugates? What happens when it is missing? What is an example of this?
It protects them from uptake and degradation.
When missing, the internal sugar residue, galactose, is recognized by asialoprotein receptors on hepatocytes for destruction: e.g. old RBCs in the blood loose their sialic acid residues and are removed from the blood
What role do surface oligosaccharides play with regards to the influenza virus? What does Tamiflu and Relenza do?
HA (hemagglutinin binds sialic acid) and N (neuraminidase cleaves sialic acid) are viral lectins that recognize carbs on the cell surface to enter and infect (HA) and to bud = leave the cell (N).
Tamiflu and Relenza are sugar analogs that target N.
What are other agents that have lectins that recognize surface carbs?
Bacteria, toxins
What are ABO blood types due to?
A core glycan is attached to all RBCs’ surface at a glycoshingolipid and is either attached to α-N-acetylgalactosamine (Nac: type A), α-d-galactose (Gal: type B), or neither (H: type O)
What is special about the ABO blood groups?
Very ancient system and exists intact in chimpanzees
What is the naming convention for fatty acids?
of Cs : # of unsaturated bonds
How is energy stored in adipose tissue? Is it polar?
Tryaglyceride: glycerol with 3 fatty acids
NEUTRAL!
What are 5 types of sphingolipids and the head group of each?
- Ceramide: H
- Sphingomyelin: phosphocholine
- Glycolipids=Glucosylcerebroside: glucose
- Lactosylceraminde: tetrasaccharide
- Ganglioside: complex oligosaccharide
Why do sphingolipids look similar to glycerophospholipid?
Because the sphingosine backbone looks like a fatty acid chain (it has a long CH chain)
What types of lipids do the A/B/O antigens attach? Where?
Sphingolipids (on the polar head group)
What are the 2 types of glycolipids?
- Sphingolipids
2. Galactolipids = sulfolipids (w/ glycerol backbone)
What is the shape of the individual units of the micelle?
Wedge
What drives micelle/lipid bilayer formation?
The hydrophobic effect to create more entropy in water environment
What is the shape of the individual units of the lipid bilayer?
Cylindrical
What kind of forces hold the lipid bilayer together?
Weak molecular forces
How can lipids transfer from one leaflet of the bilayer to the other? Why is this important?
Due to the high activation energy of this
process, there are proteins in the cell membrane that catalyze transbilayer translocations, called
flippases, floppases, and scramblases.
This unfavorable is a crucial process, considering that the lipid molecules
are synthesized on the interior of the cell and would need some assistance getting to the outer leaflet.
What are the 3 types of membrane proteins? Describe each
- Peripheral/extrinsic: held to membrane by weak molecular forces
- Integral proteins: embedded in the membrane
- GPI-anchored membrane proteins: soluble proteins covalently bound to membrane
What can detach a peripheral membrane protein?
Changes in pH, chelating agent, urea, or w/ salts because they are attached by many electrostatic interactions
What can detach an integral membrane protein?
Use detergent
Explain the movement of solutes down their concentration gradient with ΔG
ΔG = RTln [S2]/[S1]
- When [S1]>[S2]: ΔG[S2]: ΔG>0
- When [S1]=[S2]: ΔG=0
What can we say of ln of x when x
lnx is negative
Explain the movement of solutes down their concentration gradient with ΔG when there is also a change in electrochemical potential
ΔG = RTln [S2]/[S1] + Z.F.ΔPsi
Z: valence
Psi: ΔV
What is the definition of permeable/impermeable?
If the solute can cross the membrane at such a rate that is favorable to biological processes, then the membrane is said to be permeable to that solute.
If the rate at which the solute crosses the membrane is too slow to support biological processes, even the electrochemical gradient is thermodynamically favored, it is said to be
impermeable.
What molecules undergo simple diffusion across the lipid bilayer? 2 types
- Hydrophobic molecules: O2, CO2, N2, Benzene
2. Small uncharged polar molecules: H2O, urea, glycerol
What molecules cannot pass the lipid bilayer? 2 types
- Large uncharged polar molecules: glucose, sucrose
2. Ions
Why does simple diffusion not happen for certain molecules?
Because the activation energy for it to occur is too high
What are the 3 ways for molecules to cross the lipid bilayer?
- Simple diffusion
- Facilitated diffusion
- Active transport
Explain facilitated diffusion. What are the 2 types?
Transporters, permeases, exchangers lower the activation energy and move molecules down their concentration gradient
- Uniport: moves 1 solute in 1 direction
- Co-transport: symport or antiport
What is an example of antiport facilitated diffusion?
- CO2 enters RBC at respiring tissues
- CO2 reacts with H2O to producse HCO3-
- HCO3- exits RBC via the bicarbonate-chloride antiportr
- At the lungs, HCO3- re-enters the RBC while Cl- exits to alleviate the charge imbalance
- HCO3- reacts with H+ to produce CO2 and H2
- CO2 diffuses out of the cell
Explain active transport. What are the 2 types and an example for each?
The free energy to move the process in the forward direction is supplied by
ATP hydrolysis by coupling the thermodynamically unfavorable diffusion event to a very
thermodynamically favorable.
- Primary: the transporter protein is also catalyzing the hydrolysis of ATP (eg: Na+ K+ ATPase)
- Secondary: the diffusion of one solute is dependent on the concentration gradient of another
solute (sometimes having been established by the hydrolysis
of ATP) (eg: lactose permease to bring lactose inside the BACTERIA)
What is the best example of primary active transport?
Na/K ATPase: Na+ and K+ are both
pumped against their concentration gradients in order to establish an electrochemical potential across the cell membrane. This is such an important
process that some cells spend 75% of their energy on this process alone (think neurons).
What is the best example of secondary active transport?
Lactose permease transporter: a proton pump expels hydrogen ions out of the cell by hydrolyzing ATP, and as a result lactose can be taken up through
a symporter with the proton concentration gradient providing the free energy for diffusion.
This happens in bacteria, not humans.
Explain what transport mechanisms bring glucose to the gut?
- The Na/K ATPase keeps the
sodium concentration low inside the cell to keep driving glucose uptake (primary active transport). - glucose enters on
the apical surface of the cell through a sodium-glucose cotransporter where sodium moves down its
gradient and glucose moves up it its gradient (secondary active transport). - Glucose diffuses across the basolateral surface of the cell into the bloodstream via the GLUT-2 transporter (facilitated diffusion), since the blood has a much lower glucose concentration than the
cytoplasm.
What does the reducing potential of sugars come from?
The ability of the anomeric carbon to undergo mutarotation
What are the 2 types of sphingolipids?
Sphingosine backbone + fatty acid + PO4-choline OR sugar
What are asialoprotein receptors? Where are they found?
Asialoprotein receptors on hepatocytes recognize glycoconjugates for destruction: e.g. old RBCs in the blood loose their sialic acid residues and are removed from the blood
What are the 4 biological roles of sugars?
- Fuel
- Energy storage
- Signaling
- Cell structure
How to quickly tell if a sugar is L or D?
Looks at chiral C farthest from C=O (at the bottom of the Fisher projection):
- If OH is on the right: D
- If OH is on the left: L
What type of rxn is a glycosidic bond formation?
Condensation
What is galactosemia/fructosemia? What are the consequences?
Lack the enzymes to metabolize galactose and fructose: can be life-threatening
What is heparin sulfate? Where can you find it?
Highest negative charge density of any biological macromolecule, is found attached to proteoglycans and glycoproteins
Which AA can be part of phospholipids? What kind?
Serine
Glycerophospholipids
How does the lengths of the fatty acids in the lipid bilayer affect membrane fluidity?
Fluidity decreases when lengths increase
Can the heads groups of membrane lipids have a net positive charge? Neutral?
+: NOPE
Neutral: yes
Is facilitated diffusion energetically unfavorable?
NOPE
What is the difference between galactosemia and lactase deficiency?
Lactase deficiency would mean that you’re not able to break down lactose into glucose and galactose
Galactosemia means that you cannot process galactose once it enters the cells (it can still be absorbed in the small intestine though)
Do you necessarily need an anomeric C for a glycosidic bond?
YUP
What is the effect of facilitated diffusion on the free energy change? on the activation energy?
No effect on free energy change
Lowers activation energy
What is the only sphingolipid that is a phospholipid?
Spingomyelin
Are glycosaminoglycans O-linked or N-linked?
Both!
What are the 3 sugar moeities for the ABO blood groups?
- A: α-N-acetylgalatosamine
- B: α-D-galactose
- O: H antigen only
What does the bond between the sphingosine backbone and the fatty acid resemble? It’s the same one…
Peptide bonds!
