Nucleic Acids, Sugars, and Lipids

Question 1

what is the structure of a nucleic acid?

• building blocks?
• bases?
• where are bonds formed? what are these bonds called?
• what is the backbone?

Answer 1

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)

Question 2

compare and contrast the features of RNA and DNA

Answer 2

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

Question 3

what is the structure of sugars

what is an epimer? how are they interconverted?

Answer 3

(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

Question 4

what is the structure of lipids

Answer 4

fatty acid and glycerol

Question 5

Understand the varied roles of sugars in metabolism and protein structure

Answer 5

• 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

Question 6

Identify the major membrane lipids and understand their effect on membrane fluidity

Answer 6

cholesterol interacts with phospholipid tails

glycolipids have sugar head group
-one sugar is cerebroside and complex sugar is ganglioside

Question 7

Appreciate the asymmetry of cellular membranes

Answer 7

Outer leaflet
More phosphatidylcholine
and sphingomyelin
Glycolipids

Inner leaflet
More phosphatidylserine and 
Phosphatidylethanolamine
phosphatidylinositol 
Important in apoptosis and cell signaling

Question 8

Understand the roles of lipids in protein structure and cellular function

-what are common fatty acids in the membrane?

Answer 8

-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

Question 9

Compare the size of the human DNA vs mitochondrial DNA

Answer 9

nuclear DNA is 3 million base pairs and 23 pairs of haploid chromosomes

mitochondrial DNA is 37 genes

Question 10

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 ?

Answer 10

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).

Question 11

describe main characteristics of DNA strand

-direction
-strands
what is the sense strand?

Answer 11

-strands are antiparallel with 5’ to 3’ direction that reverses on the next strand

the sense strands is the coding strand

Question 12

prokaryotic DNA is circular and forms supercoils but Eukaryotic DNA is linear and forms supercoils, why is this?

-what relieves torsional stress

Answer 12

Eukaryotic is tethered to scaffold of proteins and other attachments so it coils like it is linear

-stress is relieved by topoisomerases

Question 13

describe the abundance and functions of RNA

Answer 13

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

Question 14

RNA is single stranded but…

-what are some of these structures

Answer 14

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

Question 15

clinical correlation for DNA

Answer 15

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

Question 16

how do you distinguish L vs D sugars?

what about alpha and beta?

Answer 16

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

Question 17

how are sugars linked?

bonds for lactose and sucrose?

glycogen?

cellulose?

Answer 17

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

Question 18

N-linked vs O-linked sugars

Answer 18

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

Question 19

proteoglycans

Answer 19

glycoproteins with repeating dissacharides

modifications are important for structure of extracellular matrix

Question 20

key functions of cellular membranes

Answer 20

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)

Question 21

what are sphingolipids

what is sphingomyelin and where is it found?

Answer 21

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

Question 22

movement from one leaflet to the other requires?

Answer 22

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

Question 23

what things change the characteristics of the lipid membrane?

Answer 23

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

Question 24

what is a lipid raft? function?

Answer 24

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

Question 25

what is a cavolae

Answer 25

Caveolae
Invaginations on the surface of the plasma membrane
Formed via interaction between protein caveolin and cholesterol
Function?

Question 26

which membrane proteins are anchored by covalent lipid modifications

Answer 26

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

Question 27

Synthesis of membrane lipids

Answer 27

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

Question 28

nuclear envelop and RER

Answer 28

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.

Question 29

membranes of mitochondria

Answer 29

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.

Question 30

clinical correlation of sphingolipidoses

Answer 30

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

Question 31

what is a nucleoside vs a nucleotide?

Answer 31

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