Nucleic Acids, Sugars, and Lipids Flashcards
what is the structure of a nucleic acid?
- building blocks?
- bases?
- where are bonds formed? what are these bonds called?
- what is the backbone?
building blocks are:
phosphate group, sugar ring, and nitrogenous base
- bases in RNA are: A, C, U, G
- bases in DNA are: A, C, T, G
bases are pyrimidines: CUT or purines (2 rings) : A, G
- 3’ OH attaches to 5’ of phosphate on next carbon and these bonds are called phosphodiester bonds
- phosphate- sugar forms the backbone with the nitrogenous bases on the inner space (block from water so that H bonds are stronger)
compare and contrast the features of RNA and DNA
RNA contains the bases A,C,G,U, attached to a ribose sugar (2’ OH)
-this 2’OH also makes it more degradable / susceptible to hydrolysis
DNA has bases A, C, G, T attached to deoxyribose sugar
what is the structure of sugars
what is an epimer? how are they interconverted?
(CH2O)n
hexoses or pentoses are common
can be aldehydes or ketones
usually in the D form
epimers differ at ONLY one position of a chiral carbon
-interconverted by epimerases
what is the structure of lipids
fatty acid and glycerol
Understand the varied roles of sugars in metabolism and protein structure
- sugars can have added NH2 group and this group can be acetylated or sulfated —> which is important for extracellular matrix
- sugars can be linked to proteins and are called glycoproteins—> this provides structural specificity in extracellular matrix . preoteoglycans is the name for glycoproteins that play important roles in ECM
- sugars also can be modified to form human blood groups. oligosaccharaides are linked to proteins or lipids
Identify the major membrane lipids and understand their effect on membrane fluidity
cholesterol interacts with phospholipid tails
glycolipids have sugar head group
-one sugar is cerebroside and complex sugar is ganglioside
Appreciate the asymmetry of cellular membranes
Outer leaflet
More phosphatidylcholine
and sphingomyelin
Glycolipids
Inner leaflet More phosphatidylserine and Phosphatidylethanolamine phosphatidylinositol Important in apoptosis and cell signaling
Understand the roles of lipids in protein structure and cellular function
-what are common fatty acids in the membrane?
-membranes consist mostly of phospholipids: 2 fatty acids, glycerol, phosphate. alcohol
common fatty acids in the membrane:
- saturated (no double bonds)
- unsaturated (mostly cis)
- polyunsaturated fatty acids
- also have: phosphoglycerides with different head group
- lots of sphingolipids (aka ceramics) which are amino group plus FA
- cholesterol
- glycolipids
Compare the size of the human DNA vs mitochondrial DNA
nuclear DNA is 3 million base pairs and 23 pairs of haploid chromosomes
mitochondrial DNA is 37 genes
describe the hydrogen bonds in RNA/ DNA
-how do they match up
-how do we know?
what does this contribute to?
how do we estimate Tm ?
hydrogen bonds form between the nitrogenous bases
A=T is 2 bonds
G-C is 3 bonds thus it is held stronger.
ration of A:T and G: C is fairly 1:1
in fact the melting point of DNA can be determined by the amount of G-C in a linear relationship
Tm is halfway of the curve plotted of absorption vs. temperature (increase absorption as increase in temp bc becomes more single stranded)
When DNA is heated, the temperature at which one half of the helical structure is lost is defined as the melting temperature (Tm).
describe main characteristics of DNA strand
-direction
-strands
what is the sense strand?
-strands are antiparallel with 5’ to 3’ direction that reverses on the next strand
the sense strands is the coding strand
prokaryotic DNA is circular and forms supercoils but Eukaryotic DNA is linear and forms supercoils, why is this?
-what relieves torsional stress
Eukaryotic is tethered to scaffold of proteins and other attachments so it coils like it is linear
-stress is relieved by topoisomerases
describe the abundance and functions of RNA
1) ribosomal is the most abundant (80%) and is a structural component of ribosomes
2) transfer RNA (15%) is matched up to a specific aa for growing the polypeptide chain during translation
3) messenger RNA (5%) is the template for protein synthesis
4) small nuclear RNA are used for splicing
and
small nucleolar RNA are used for RNA processing
RNA is single stranded but…
-what are some of these structures
can form extensive secondary and tertiary structures through intrastrand base pairing
need to know:
hairpin is a secondary structure
stem loop is a secondary structure
tRNA forms tertiary structure as it folds to hold aa on one end (at 3’) and the mRNA at the other end
clinical correlation for DNA
systemic lupus erythematosus
- autoantibodies to nucleic acid are induced
- immune complex btwn nucleic acid and autoantibodies cause inflammation
-autoimmune disease is chronic and affects kidneys, hematopoietic system, skin, joints, and lungs
how do you distinguish L vs D sugars?
what about alpha and beta?
D sugar:
go to furthest asymmetric carbon from aldehyde group; if OH is on the right side, then it is a D form
alpha sugar:
look at OH and see if it is on the opposite plane as the CH2OH group
how are sugars linked?
bonds for lactose and sucrose?
glycogen?
cellulose?
sugars linked by O- glycosidic bonds
label by the Carbons being linked and whether alpha or beta
lactose: galactose and glucose
beta (1, 4) linkage
sucrose: fructose and glucose
alpha (1, 2) linkage
glycogen is alpha (1, 4) linkages with branches at alpha (1, 6) of glucose only
cellulose cannot be broken down because beta (1, 4) linkage of glucose only
N-linked vs O-linked sugars
N-linked is amide nitrogen of asparagine residues (bc asparagine has N in R group) which is a common pentasaccharide core
O linked is on the side chain of serine and threonine at their OH bc these 2 aa have O in R groups
proteoglycans
glycoproteins with repeating dissacharides
modifications are important for structure of extracellular matrix
key functions of cellular membranes
1) compartmentalization (mitochondria, nuclei, lysosomes)
2) anchor proteins to the membrane
(cell signaling)
3) intracellular and extracellular transport (secretory vesicles)
4) electrochemical/membrane potential (energy production)
what are sphingolipids
what is sphingomyelin and where is it found?
Glycolipids are molecules that contain both carbohydrate and lipid com- ponents. Like the phospholipid sphingomyelin, glycolipids are deriva- tives of ceramides in which a long-chain fatty acid is attached to the amino alcohol sphingosine. They are, therefore, more precisely called glycosphingolipids. [Note: Ceramides, then, are the precursors of both phosphorylated and glycosylated sphingolipids.] Like the phospholipids, glycosphingolipids are essential components of all membranes in the body, but they are found in greatest amounts in nerve tissue. They are located in the outer leaflet of the plasma membrane, where they interact with the extracellular environment. As such, they play a role in the regu- lation of cellular interactions, growth, and development.
The backbone of sphingomyelin is the amino alcohol sphingosine, rather than glycerol. plist phosphate and choline head group
-myelin sheath component and in the outer leaf of plasma membrane
movement from one leaflet to the other requires?
Movement from one leaflet to another requires “flippases” and ‘floppases”
Energy dependent
Flippases move phosphatidyl serine (PS) from the outer leaflet to the inner leaflet against a concentration gradient
Floppases transport phosphatidylcholine (PC) and sphingolipids (SL) against concentration gradients in the opposite direction
what things change the characteristics of the lipid membrane?
Increasing the length of the FA chain decreases fluidity
High cholesterol decreases fluidity
Increasing polyunsaturated FA’s will increase fluidity
Unsaturated FA’s cannot pack as tightly as those that are saturated
what is a lipid raft? function?
Microdomains enriched in cholesterol, gangliosides, sphingomyelin, & specific membrane proteins
Lipids primarily saturated
Decreased fluidity
Many proteins clustered in lipid rafts are involved in cell signaling
what is a cavolae
Caveolae
Invaginations on the surface of the plasma membrane
Formed via interaction between protein caveolin and cholesterol
Function?
which membrane proteins are anchored by covalent lipid modifications
Some membrane proteins are anchored by covalent lipid modifications
Fatty acids myristate (14:0) or palmitate (16:0)
Src kinase
Isoprenyl groups such as farnesyl
Ras G protein
Glycosylphosphatidyl-inositols (GPI) anchors are used for proteins on the extracellular surface of the membrane
Synthesis of membrane lipids
Phospholipids synthesized in membranes of the endoplasmic reticulum (ER)
Glycolipid synthesis starts in the ER and final addition of carbohydrates is performed in the Golgi apparatus
Cholesterol is synthesized in the membranes of the ER
nuclear envelop and RER
The outer membrane of the nuclear envelope is contiguous with the rough endoplasmic reticulum. Both the RER and NOM contain phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine, although the NOM has a significantly higher proportion of proteins with a lower proportion of carbohydrates than does the RER.
membranes of mitochondria
The inner membrane of mitochondria is similar in lipid composition to the membrane of bacteria.
In pig heart mitochondria, phosphatidylethanolamine makes up the majority of the inner mitochondrial membrane at 37.0% of the phospholipid composition.
Phosphatidylcholine makes up about 26.5%, cardiolipin 25.4%, and phosphatidylinositol 4.5%.
In the inner mitochondrial membrane, the protein-to-lipid ratio is 80:20, in contrast to the outer membrane, which is 50:50. The outer membrane is devoid of cardiolipin but contains greater proportions of phosphatidylinositol and phosphatidylserine than the inner membrane.
clinical correlation of sphingolipidoses
Lipid storage disorders involving disruption of sphingolipid metabolism
e.g. Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs disease and Metachromatic leukodystrophy.
Overall incidence of 1 in 10,000
More common in certain populations such as Ashkenazi Jews
Generally fatal by age 1 to 5 years for infantile forms if no treatment available
Progression may be mild for juvenile- or adult-onset forms
what is a nucleoside vs a nucleotide?
A nucleoside consists of a nitrogenous base covalently attached to a sugar (ribose or deoxyribose) but without the phosphate group.
A nucleotide consists of a nitrogenous base, a sugar (ribose or deoxyribose) and one to three phosphate groups.
Nucleoside = Sugar + Base Nucleotide = Sugar + Base + Phosphate
