Exam 2: Macromolecules: Carbohydrates Flashcards
characteristics of macromolecules
- building blocks of living organisms
- polymers of individual subunits/monomers
- all contain carbon and hydrogen, most oxygen
- C-C bonding forms rings or chains that functional groups can attach to
- functional groups affect structure and function
Carbon functions
- forms 4 bonds for stability
- able to bind other carbons
- forms complex structures such as rings and chains
- able to form single as well as multiple bonds
- HAVE CHIRALITY
what does chirality mean?
a carbon with 4 different bonds
what are stereoisomers?
4 unique groups arranged in different ways
- same formula, dif 3D shape
D (R) isomers rotate light how?
clockwise
L (S) isomers rotate light how?
counterclockwise
Which form do racemic mixtures have
both D and S
Why is stereochemistry important in pharmecuticals?
- stereoisomers have same chemical formula and attachments, but differ in spatial arrangements
- effects binding ability and affinity
- binding poorly to the target effects the efficacy
- binding a site other than the target site can be disastrous
History of thalidomide in US
- Taussing : treated these people
- Kelsey: FDA, refused to do this, both said no
not a lot of cases in US. many elsewhere
Thalidomide
developed to treat nausea
- R version is sedative, calms people down
one form effective and the other not
- R worked well in pregnant women
- S is a terotegen:
causes defects in unborn in development of arms and legs receptors
4 main categories of macromolecules
carbohydrates, lipids, proteins, nucleic acids
Carbohydrate functions
- energy, storage, structure
- cell recognition and communication
- modifies proteins effecting
- structure/folding, enzyme kinetics,
turnover/degradation
Structure of carbohydrates
monomer: CH2O
carbohydrate terminology
ose: refers to sugars
mono, di, poly refers to degree of polymerization
Two examples of simple sugars
glucose and fructose
what is the difference between glucose and fructose?
glucose is an aldose sugar (carbonyl on end)
fructose is a ketose sugar (carbonyl in middle)
similarities between glucose and fructose
both D-isomers, right handed
we only use Right form
If many chiral carbons how do we know what form it is in?
highest chiral carbon, look at the OH group
- if written on the right it is right handed
What if bacteria could make left handed form in protective capsule?
it is better for them, they get added defense that we cannot break down
What if you ate breakfast and all sugars were left handed?
enzymes would not fit into the active site
transporters could not bind to get it out so it would stay in the gut
- attracts water to it since hydrophilic so you get diarrhea
alpha form of carbohydrates
opposite sides
OH in the down position
beta form of carbohydrates
same side
OH in up form
anomeric C
one with carbonyl
forms the ring
Binding to find Di/Polysaccharides
condensation, dehydration rxn to remove water (OH from one, H from other) and combine sugars
What type of bond is between sugars
what things have these bond
alpha 1-4 glycosidic bond
starch and sucrose
What types of bonds does glycogen have?
a 1-4 and a 1-6 glycosidic bonds
gets branched structure
glycogen
primary carbohydrate storage molecule
what type of bonds does lactose have?
B1-4 glycosidic bond
Why might someone who has no problem digesting sucrose or starch have difficulty with lactose?
need different enzyme for B bonds
need lactase
How is lactase made?
in Small Intestine from mucosa and it can dec over time in some cases
- causing an intolerance to lactose
amylase
breaks down all alpha bond
Where is lactase only produced?
the mucosa of the small intestines
When does lactose intolerance occur?
when your body stops producing lactose
Is lactose intolerance permanent?
it can be temporary or genetic/developmental
What is the role of lactose in pharmecuticals?
it is a common filler
people may think having a reaction to the drug itself, but really it is the lactose so you should see if atient is lactose intolerant first
What are 3 broad categories of carbohydrate/sugar modifications
sugar alcohols, acidic sugars, and amino sugars
What are sugar alcohols formed by and where does this occur?
formed by reduction of the carbonyl group
occurs in the polyol pathway
Sorbitol
- effective osmole
- used for storage in celll and can be metabolized forward to fructose or back to glucose
Inositol
- utilized in signaling, myelin attachment, and nerve function
- cyclicAMP, PIP2
What type of relationship is between sorbitol and inositol
inverse relationship
- as one increases, the other decreases
inositol is an isomer of…
sorbitol
what happens when you get an increase in sorbitol?
the cell brings in water and osmotic pressure increases, you have to regulate it because you do not want too much
Two ways glucose is transported into the cell
- insulin independent proteins
- insulin dependent proteins
insulin-independent transporter proteins maintain…
the basal level of glucose required for cell survival
What happens to excess glucose
it enters the polyol pathway
What has a high percentage of insulin-independent transporters?
kidney, retinal, nerve tissue
Which proteins can be upregulated insulin-dependent proteins or insulin-independent proteins?
insulin-dependent proteins
When you raise the amount of glucose in the blood you get lots of _________ in the liver
insulin-dependent transport proteins
Which transport proteins can not be upregulated
insulin-independent transport proteins
How can you get an increase in insulin-independent transport proteins?
you are pulling in sugar at the basal level, but when you increase BP cells pull in more sugar than they can handle
- the excess sugar goes to the polyol pathway
How are acidic sugars formed?
the oxidation of the 6’ OH group or the 1’ carbonyl group to a carboxyl group
Where does the modification to acidic sugars occur?
many tissues, but highest in the liver, kidneys, RBCs
Example of an acidic sugar
glucuronic acid
Glucuronic acid
detoxifying agent
- conjugates with molecules to increase solubility and transport or excretion
What is a byproduct of RBC and what does it do?
bilirubin
- it is broken down by hemoglobin and the liver will conjugate it
- conjugation increases solubility
How are amino sugars formed?
the replacement of an OH group with an NH2
2 examples of amino sugars
glucosamine and galactosamine
What do glucosamine and galactosamine create?
the matrix in the connective tissue
What increases the structural nature in amino sugars?
beta bonds between alternating sugars
2 more examples of amino sugars
hyaluronic acid and chondroitin sulfate
hyaluronic acid - amino sugar
least crosslinked, weakest, more fluid
- connective tissue in the skin
chondroitin sulfate
more cross linked
glucosamine and chondroitin sulfate are used for?
supplements in joints
- CARTILAGE in joints
cartilage is imbedded with calcium phosphate to get bone but the fibers made from amino sugars are more alkaline
Purpose of the glycosylation of proteins (6)
- modify/regulate protein function
- stabilize proteins in the serum
Fc fragment in antibodies - makes live longer - initial protein folding
- cell recognition and binding to membrane proteins (blood types, inositol as second messenger)
- increased hydration of molecule (mucous)
- involved in stabilizing structure (connective tissue)
Glycoprotein vs proteoglycan
proteoglycans are more protein than sugar, glycoproteins are more sugar than protein
Proteoglycans
subset of glycoproteins
- mainly found in connective tissue (chondroitin)
- higher in protein content (85% vs 50% in glycoproteins)
How can the glycosylation be categorized (2 ways)
N-linked or O-linked
N-linked glycosylation
carbohydrate attaches to asparagine group
- deals with recognition, binding, stability (antibodies)
O-linked glycosylation
attachment to a serine or threonine
- has diverse functions (mucins)
