Carbs and Lipids (Final) Flashcards
1
Q
What are 3 names for carbohydrates?
A
glycans, saccharides, sugars
2
Q
Describe the structure of glucose.
A
- 6 carbons
- 5 have hydroxy groups, 1 has a carbonyl
- aldose sugar
- All but C1 and C6 are chiral, 4 stereocenters, 24 = 16 conformers for a 6 carbons sugar
3
Q
What conformer of glucose exists in our body?
A
D - glucose
4
Q
How do you identify D and L glucose?
A
- look at carbon #5 (furthest from carbonyl)
- observe if it looks like D-glyceraldehyde or L-glyceraldehyde
- OH on right = D
- OH on left = L
5
Q
What are epimers?
A
sugars that differ by stereochemistry at 1 carbon
6
Q
What is an aldose?
A
a sugar that has an aldehyde on the end
7
Q
What is a ketose?
A
- a sugar that has a ketone instead of an aldehyde
- 1 less chiral center
- 23 - 8 possible isomers
8
Q
What two functional groups react in aldoses? (To cyclize)
A
alcohol + aldehyde react to form a hemiacetal
9
Q
What two functional groups react in ketoses? (To cyclize)
A
alcohol + ketone react to form a hemiketal
10
Q
How can you identify R or S configuration?
A
- look at C2
- R = OH on right, down on ring
- S = OH on left, up on ring
11
Q
How are the carbons numbered in a ring / linear glucose?
A
- top to bottom 1 - 6 linear
12
Q
How does glucose cyclize
A
13
Q
How does fructose cyclize?
A
14
Q
What is the anomeric carbon?
A
- the carbonyl carbon
- may be alpha or beta
- alpha = below the ring
- beta = aBove the ring
- this is called the configuration of the anomeric center because interconversion requires bond breaking
15
Q
Describe the alpha and beta anomers of glucose. What percent of each exists?
A
- alpha and beta forms freely interconvert - the aldol reaction is a very reversible process (glucose is constantly changing between ring and linear forms)
- D-glucose is 63% beta and 37% alpha
16
Q
What is required for interconversion between chair conformers?
A
- interconversion does not require bond breaking (conformations)
17
Q
Why is beta more stable?
A
- in the chair conformation the beta version (aBove) is more stable because the bulky groups are equatorial
18
Q
How are sugars connected?
A
Glycosidic linkages - bonds connecting anomeric carbon to an alcohol oxygen
19
Q
How does a glycosidic linkage change a sugar?
A
- when a glycosidic linkage forms you can no longer convert alpha and beta
- when you can interconvert this is called a reducing sugar
- When you can’t interconvert this is a non-reducing sugar
20
Q
How do you name a glycosidic linkage?
A
- glucose (β/α) (1-4) glucose
- 1 is the anomeric carbon, the second number is the number of the c it is bonded to
21
Q
What are the 3 types of glycogonjugates?
A
- proteoglycans - mostly carbs
- peptidoglycans - mostly carbs
- glycoproteins - mostly proteins
22
Q
What are proteoglycans?
A
- mostly glycans
- found in our extracellular matrix
- highly charged (have sulfated sugars often GAGs)
23
Q
What are peptidoglycans?
A
- majority carbohydrates, found in bacterial cell wall
- they are what is stained in gram positive bacteria
24
Q
What are gram positive/gram negative bacteria?
A
- Gram positive - bacterial cell wall has no outer membrane, peptidoglycans are stained in a gram stain
- Gram negative - bacterial cell wall has an inner and an outer membrane, with a thin layer of peptidoglycans in the middle, this layer is not stained in a gram stain
25
Describe the structure of peptidoglycans.
* GlcNAc β(1 - 4) MurNAc (N-acetyl Muraminic acid)
* repeats this disaccharide unit
* peptide is attached via amide linkage to the carboxyl off of 3'C of MurNAc
26
What process makes bacterial cell walls protective?
* peptide crosslinks of peptidoglycans
* peptide crosslinks prevent glycans from sliding across each other, this makes bacterial cell walls protective
27
What forms the glycopolymer in peptidoglycans?
transglycosylase
28
What forms peptide crosslinks in bacteria?
transpeptidase
29
What are glycoproteins and what are the types?
* made of mostly protein with some sugars added
* may be N-linked or O-linked
30
What is common between N-linked and O-linked glycoproteins?
* they are secretory proteins
* there is diversity in what sugars are attached
31
Describe N-linked glycoproteins.
* sugar is β-linked to Asn (asparagin)
* glycosylation occurs within a consensus sequence
* N - X - S/T (must be one aa away from an S/T, X can be any aa except proline)
* occurs in the lumen of the ER, co-translational, as it is threaded through the ribosome
32
Describe O-linked glycoproteins
* sugar is α linked to serine and threonine
* there is no consensus sequence
* occurs in the golgi
* sugars are added one at a time using UDP- sugar donors
33
Describe specifically how N-linked glycoproteins are added.
* 14 unit oligosaccharide is synthesized on a lipid donor
* transferred (en bloc = linked together) to Asn
* 14- sugars are trimmed
* other sugars are added
34
What class of antibiotics is penicilin? Describe how this class functions.
β - lactam
* they are covalent inhibitors
* transpeptidase cant form cross-links, and this significantly weakens the cell wall
35
What is the general goal of antibiotics?
to target something in a bacterial cell that is not present in our cells - (cell wall!)
36
How do β-lactam antibiotics function?
* transpeptidase attacks the amide bond of a β-lactam instead of the amide bond in D-ala D-ala (glycoproteins)
* this reaction has slow hydrolysis
* Tpase is trapped by β-lactam and unable to performed peptide cross-links
* weakens bacterial cell wall
* cell death
37
How is β-lactam resistance introduced?
* bacterial cells produce β-lactamase which opens the ring on β-lactams
* Transpeptidase does not bind to the ring opened product
38
How do we overcome β-lactam resistance in bacteria?
* treat people with a cocktail of antibiotics including β-lactamase inhibitors
* people often treated with Augmentin
* clavulanic acid - β-lactamase inhibitor
* amoxycilin - β-lactam
39
What is vancomycin?
* antibiotic binds to substrate D-ala D-ala,
* blocks the access of T-pase through capping D-ala, D-ala with 5 H-bonds
* T-pase is unable to form crosslinks
* weakened cell wall, cell death
40
What is the peptide chain attached to in a peptidoglycan?
* peptide sequence is attached via an amide linkage to the carboxyl off of the 3'C of MurNAc
41
List the 5 genes involved in vancomycin resistance.
* Van R - transcription factor - activates VanHAX
* Van S - cell surface receptor for vancomycin
* Van H - synthesizes D-lactate from pyruvate
* Van A - couples D-lac + D-ala
* Van X - cleaves and destroys D-ala - D-ala
42
Describe lipids and biological membranes. What are some characteristics of these molecules?
* not polymers
* aggregate - non-covalently
* large structural variability
* hydrophobic
* low water solubility
43
How do lipids aggregate?
non-covalently
44
What are some functions of lipids?
membrane, energy stores, signaling
45
What are 7 types of lipids?
1. Fatty acids
2. Triaglycerols /triglycerides
3. Glycerophospholipids
4. Sphingolipids
5. Steroids
6. Isoprenoids
7. Eicosanoids
46
Describe fatty acids.
* basic component of a lipid
* carboxylic acid with long hydrophobic chain
* may be saturated or unsaturated
* 12:4
* 12 carbons, 4 double bonds
47
What is common to all natural fatty acids?
* cis double bonds
* trans-fats not natural
48
Describe a saturated fatty acid.
* C20:0 - no double bonds, “saturated” with H
* melting point increases as length increases
* Higher mp = better packed together
49
Describe an unsaturated fatty acid.
* kinks in the structure - less efficient packing
* lower mp
* C20:4 has a lower mp than C20:0
50
Describe triacylglycerols/triglycerides.
* energy stores
* metabolizing lipids = slower, but more efficient
* fatty acid triesters of glycerol
* can have 3 fatty acids attached
51
What are glycerophospholipids?
* major component of membranes
* glycerol + phosphate + fatty acids
52
What breaks down glycerophospholipids?
phospholipases
PLA2, PLAC, PLAD
53
What is the structure of glycerophospholipids?
54
What are sphingolipids? What do they form?
* contain a sphingosine (shown below)
* combine with an N-acyl fatty acid (fatty acid bound to the NH3 of sphingosine) to form ceramides
55
What are ceramides?
* Made of a sphingosine and an N-acyl fatty acid
* Ceramide + phosphocholine = sphingomyelin (main component of myelin sheath)
* Ceramide + sugar = cerebroside
* Ceramide + oligosaccharide = ganglioside (important for cell- cell communication)
56
Describe the function of gangliosides.
* the lipid portion is embedded in the membrane and the oligosaccharide remains on the outside of the cell (this is how they are involved in cell-cell communication)
57
Describe the structure of steroids.
* four fused non-planar rings
* -one steroids have a carbonyl on A
* -ol steroids have hydroxyl on A
58
What is an important steroid?
cholesterol
59
describe cholesterol.
* makes up 40% of our plasma membrnes
* amphiphilic - weakly
* more rigid than other membrane lipids (causes a less fluid membrane)
* makes up steroid hormones
60
What are 4 things derived from cholesterol?
* Steroid hormones:
* cortisol/hydrocortisone - inflammation
* aldosterone - water excretion by kidneys
* androgens/estrogen - sexual development
* vitamin D
61
How is Vitamin D derived?
* Ergosterol/Cholesterol converted non-enzymatically by UV irradiation to Vitamin D2/D3
* Converted to active vitamin D by _enzymatic hydroxylation_
62
What are isoprenoids?
* made of 5 carbon unit (isoprene)
* ubiquinone
* Vitamin A/retinol - eyephotoreceptors
* Vitamin K - blood clotting
* Vitamin E - antioxidant
63
What is an isoprene?
64
What are eicosanoids?
* derived from arachidonic acid
* Eg: Prostacyclin, prostaglandin, thromboxanes
* Role in inflammation
65
What is important for eicosanoid synthesis and a drug target?
PGH2 synthase, a cycloxygenase enzyme (COX enzyme)
66
What do NSAIDS target?
inhibit cox enzymes, reduce prostaglandin production (an eicosanoid) , reduce inflammation
67
What are NSAIDS? What are examples?
* Non-steroidal anti-inflammatory drugs
* aspirin, ibuprofen, naproxen
68
What are the cox enzymes?
* COX 1 - constituitively expressed, found in stomach lining, protects from stomach acid
* COX 2 - expressed at sites of inflammation, directly involved in pain + inflammation
69
Describe an attempt to overcome NSAID side effects.
* aspirin, ibuprofen, naproxen - cox 1 & 2 inhibitors cause stomach ulcers if taken for too long
* Merck developed Vioxx - cox 2 inhibitor - increased heart attacks
70
What do single tailed lipids form?
micelles
71
What do double tailed lipids form?
phospholipid bilayers, liposomes
72
What are liposomes?
* solvent filled vesicle
* bilayer
* our cells are giant liposomes
73
What are the two types of diffusion within a bilayer?
* transverse - flip-flop across, rare, requires enzymes, energetically expensive
* lateral - in plane, very common
74
Describe fluidity of bilayer.
* interior in constant motion
* fluidity is temperature dependent
* cholesterol decreases membrane fluidity
75
What is an important temperature for membrane fluidity?
* transition temperature - temp below which the bilayer turns into a gel-like solid
76
What are 3 types of membrane proteins?
* integral, lipid-linked, peripheral
77
Describe integral membrane proteins.
* associate tightly with membrane
* have a transmembrane and a soluble region
* tm may be alpha helix or beta sheet
* beta sheets form beta barrels which form channels or pores
* Porins - OmpF is a beta barrel trimer
78
How can you predict the tm of an integral protein?
* _free energy of transfer of water_ of primary sequence aas
* amount of energy required to transfer from hydrophobic to hydrophilic environment
* more energy = more hydrophilic
* \>85 hydrophobi
* Ile, Leu, Val, Gly
79
What are lipid linked proteins? What are 3 types?
* covalently linked to lipid which anchors to membrane
* prenylation, fatty acylation, gpi-linkers
80
What is prenylation?
* an isoprene is attached to a cys in a CXXY motif at the C-term
* this is an ester linkage
81
What is fatty acylation?
1. Myristoylation - amide linkage at an N-term glycine
2. Palmitoylation - thioester formed at cysteine resideu
82
What are GPI-linkers?
have hydrophobic groups attached that anchor these proteins
83
What are peripheral membrane proteins/
* H-bonding or electrostatic interactions
* can be easily dissociated from the membrane
