Biochemistry Quiz I material
collagen structure
3 alpha chain polypeptides coiled around each other in a triple helix (coiled coil); well packaged, rigid, and stronger than a steel wire of same diameter
matrix metalloproteinases (MMPs)
A family of zinc-containing enzymes that break down the cornea
L-stereoisomers
All biological proteins are ______________________
sclera
All of the following ocular structures are considered part of the "vascular tunic" of the eye, except: a. iris b. ciliary body c. choroid d. sclera
choroid
All of the following parts of the eye are largely avascular (devoid of blood vessels), except: a. cornea b. choroid c. lens d. sclera
A. pH = pKa + log ([A ̄] / [HA]) 7.4 = 3.4 + log ([A ̄] / [HA]) 7.4 - 3.4 = 4 = log ([A ̄] / [HA]) 10^4 = 10000 = [A ̄] / [HA] B. 1.4 = 3.4 + log ([A ̄] / [HA]) 1.4 - 3.4 = - 2.0 = log ([A ̄] / [HA]) 10^-2 = 0.01 = [A ̄] / [HA]
Aspirin has a pKa of 3.4. What is the ratio of A ̄ to HA in: a. the blood (pH = 7.4) b. the stomach (pH = 1.4)
protonated (NH3+), unprotonated (COO-) amino has pKa of 10 so exist in protonated form
At physiologic pH (about 7.4), the amino group is ______________. The carboxylic acid group is ____________________
zwitterions
At physiological pH, amino acids are ________________
2,3-bisphosphoglycerate (BPG) - most abundant organic phosphate in the RBC
Binds to deoxy-Hg and stabilizes the T-state - decreases affinity of hemoglobin for oxygen - promotes oxygen release in the tissues during high oxygen demand
Beta-sheet
C=O and N-H residues of the peptide bond are hydrogen bonded to each other on adjacent chains (different chains or the same chain looped back on itself); flattened structure
carbonic anhydrase - spontaneously loses a proton to become bicarbonate => lower pH in tissues
CO2 is insoluble in the blood and CO2 is converted within the RBC to carbonic acid by?
pH = pKa + log (A-/HA) pH = 4.76 + log 0.1M/0.025M = 5.36
Calculate the pH of a mixture of 0.025 M acetic acid (CH3COOH) and 0.1 M sodium acetate (NaCH3COO). The pKa of acetic acid is 4.76.
Want drugs uncharged form = neutral molecule
Do we want drugs to be charged or uncharged in order to cross stomach/intestinal epithelium for absorption into the blood?
hydroxyl group
Every amino acid contains all of the following except: - amino group - carboxylic acid - hydrogen atom - hydroxyl group - variable R group
dehydration synthesis (condensation reaction)
H2O molecule is released
based on the solubility characteristics of the side chains
How are amino acids classified?
1. Nonpolar (hydrophobic), aliphatic and aromatic 2. Polar neutral (unionized) 3. Polar negatively charged (acidic) 4. Polar positively charged (basic)
How do the R-groups fall into four classes?
Only ionize to a limited extent; partially give up protons or not at all
How do weak acids/bases ionize?
Deoxyhemoglobin (T state) and oxyhemoglobin (R state) are noticably different; allosteric proteins
How does oxygen binding alter the structure of the entire hemoglobin tetramer?
Transport of H+ ions in buffer systems and elimination of CO2 by the lungs and excretion of aqueous acids in urine
How is pH maintained in the body?
determined by sequence of amino acids
How is structure of proteins determined?
Retina
How is the inner neural layer defined?
Vascular tunic
How is the middle vascular layer defined?
Fibrous tunic
How is the outer fibrous layer defined?
20
How many common amino acids are there?
9 essential for infants (histidine) 8 essential amino acids for adults
How many essential amino acids are there for infants? Adults?
myoglobin by x-ray studies
How was tertiary structure first determined in 1958?
Ground substance
Hydrophilic, highly hydrated proteoglycans, glycosaminoglycans, and glycoproteins make up the ________________ of connective tissue
pH + pOH = 14 (pOH is equal to -log [OH-]) pOH = 14 - pH pOH = 14 - 4.5 = 9.5 pOH = 9.5
If the pH of a solution is 4.5, what is the pOH?
pH is concentration dependent Keq (Ka) is not concentration dependent
Is pH concentration dependent? Is equilibrium/dissociation constants concentration dependent?
Marfan's syndrome
Mutation in the fibrillin gene causes autosomal dominant trait; disorders of cardiovascular, musculoskeletal, and ophthalmic systems ex: detached lens from weakened zonules
Bicarbonate buffer system
System converts CO2 to bicarbonate (via carbonic anhydrase), which can be carried through the blood to the lungs for exhalation
The stronger the acid
The larger the Ka, the greater the number of H+ ions liberated =
higher; lower
The stronger the acid, the ____________ the Ka (acid dissociation constant), and the _________________ the pKa
If pH < pKa, the solution is protonated. For a weakly basic drug, protonated is the ionized form.
The structure and pKa of the weakly basic drug atenolol is shown. (pKa = 9.) Determine whether this drug would be primarily ionized or unionized at a plasma pH of 7.4.
False
True or false: tertiary structure of a protein involves "local folding" exclusively through H-bonds of amino/carboxylic acid groups
True
True or false: the cornea is largely made up of evenly spaced collagen fibrils
True
True or false: the pupillary constriction is controlled by the parasympathetic nervous system.
Proline; has a secondary amino group to form pentagon
What amino acid has no primary amino group?
Extraocular muscles
What are EOM's?
alpha-helix and beta-pleated sheet
What are commonly encountered secondary arrangements?
sugars, alcohol
What are examples of nonelectrolytes?
strong acids/bases, salts (NaCl) ex: HCl
What are examples of strong electrolytes?
weak acids, weak bases ex: HC2H3O2
What are examples of weak electrolytes?
aspartATE glutamATE
What are the acidic amino acids?
Histidine, lysine, arginine HIS Lies ARe basic
What are the basic amino acids?
1. Epithelium 2. Bowman's layer (membrane) 3. Stroma 4. Descemet's membrane 5. Endothelium
What are the five layers of the cornea?
enzymes, transporters, and regulatory proteins of metabolic pathways and gene expression
What are the functional roles of globular proteins?
mechanical support control of growth and differentiation catalysis transport and storage nerve propagation immune protection
What are the roles of protein in the body?
- support the structure and clarity of the cornea - participate in the variable light refraction of the lens - initiate the transduction of light into electric signaling - generate intraocular pressure (IOP) - lyse bacteria in the precorneal tear film
What are the roles of protein in the eye?
hyaluronate (vitreous humor) chondroitin sulfate (vitreous humor) dermatan sulfate (cornea) keratan sulfate (cornea) heparan sulfate heparin
What are the six classes of GAG's?
1) outer fibrous layer 2) Middle vascular layer ("uvea") 3) Inner neural layer
What are the three "coats" of the eye?
protection, shape, EOM insertion
What are the three functions of the sclera?
transmits light retinal metabolism posterior support (gel)
What are the three functions of the vitreous body?
elastic capsule, lens epithelium, and lens fibers
What are the three structures of the lens?
miosis and mydriasis
What are the two movements of the pupil?
antiparallel and parallel
What are the two types of beta sheets?
Structure defines the function
What defines the function in proteins?
urine pH
What determines the amount of a drug being excreted?
AA sequence
What determines the functions of proteins?
pH = -log [H+] = log (1/[H+])
What does pH equal?
When exposed to oxygen, Fe2+ is considered "oxidized" to Fe3+, but is reduced back to Fe2+ once unbound
What happens to iron when exposed to oxygen?
acidic pH with increased respiratory rate to eliminate CO2; respiratory compensation
What happens with metabolic acidosis?
basic pH and decreased respiratory rate to retain CO2; respiratory compensation
What happens with metabolic alkalosis?
acidic pH with kidneys retaining bicarbonate; renal compensation
What happens with respiratory acidosis?
basic pH and kidneys eliminate bicarbonate; renal compensation
What happens with respiratory alkalosis?
measure of the strength of an acid
What is Ka?
heat shock proteins
What is an example of a molecular chaperone?
Charged forms A- (conjugate base) and HB+ (conjugate acid)
What is excreted via the urine?
uncharged forms HA (weak acid) and B (weak base)
What is reabsorbed into the blood?
compounds that can donate protons (H+) are acids compounds that can accept protons are bases
What is the Bronsted-Lowry theory?
Iron shifts from being "domed" toward histidine to being in planar configuration with the porphyrin ring low O2 binding => Fe2+ tucked away high O2 binding => Fe2+ pops out
What is the T to R transition?
Let us set the pKa to be K and the pH to be K - 1. Now, use the Henderson-Hasselbalch equation: pH = pKa + log ([A ̄]/[HA]) Substitute: K - 1 = K + log ([A ̄]/[HA]) Move K to the other side: -1 = log ([A ̄]/[HA]) Antilog both sides: 0.1 = ([A ̄]/[HA]) Replace 0.1 with a fraction: 1/10 = ([A ̄]/[HA])
What is the [A-]/[HA] ratio when a weak acid is in a solution with the pH one unit below its pKa?
Keq (Ka) = [H+] [A-]/ [HA] * predict ratio of free ions to weak acid
What is the equilibrium/dissociation constants?
electron pair acceptors are acids electron pair donors are bases
What is the lewis theory?
To take in information from the environment (light) and interpret it into a neural signal (sight)
What is the main function of the eye?
pH = -log [H+] [H+] is equivalent to the molarity of acid present in a solution When the pH is less than 7, the solution is acidic. pH = 7 it is neutral pH > 7, it is basic In this problem, there are 0.685 moles of HCl dissolved in 1.5 L H2O, making a total acid concentration of 0.457 M (mol/L). To find the answer, take the negative log of this to find that the pH = 0.34
What is the pH of a solution that contains 25 grams of hydrochloric acid (HCl) dissolved in 1.5 liters of water?
7.35-7.45
What is the pH of blood?
transport oxygen from the lungs to the tissues oxyhemoglobin (increase O2 pressure in lungs) <-> deoxyhemoglobin (decrease O2 pressure in tissues) + 4O2
What is the primary function of hemoglobin (Hb)?
unique sequence of amino acids - protein structure -function - relationship to other proteins
What is the primary structure of a protein?
protein functional groups
What is the principal buffer in plasma and RBCs?
bicarbonate-carbonic acid
What is the principal buffer in the plasma?
hemoglobin
What is the principal buffer in the red blood cells?
H2CO3 dissociates by the removal of H+ by buffering action of hemoglobin. Hemoglobin affinity for O2 reduced in presence of CO2 and H+. Oxyhemoglobin dissociates into oxygen and deoxyhemoglobin Bohr effect: O2 will disassociate from hemoglobin in response to a lowered blood pH and/or an increase in pCO2
What is the process of buffer systems of blood and exchange of O2 and CO2 with hemoglobin?
protonated (charged) HB+ unprotonated B
What is the protonated (ionized) part of a base? H+ + B <-> HB+
protonated HA unprotonated (charged) A-
What is the protonated (unionized) part of an acid? HA <-> H+ + A-
glycin
What is the smallest, most compact amino acid?
HA is the weak acid A- is the conjugate base
What is the weak acid and conjugate base? HA <-> H+ + A-
presence of inflammatory cells or increased protein content; intraocular inflammation
What makes the anterior chamber abnormal?
fibrous components, cellular components, and ground substance
What makes up the connective tissue?
Retina
What makes up the inner neural layer of the eye?
iris, ciliary body, choroid
What makes up the middle vascular layer ("uvea") of the eye?
Cornea and sclera
What makes up the outer fibrous layer of the eye?
parasympathetic nerve activity (rest and digest)
What nerve activity is miosis responding to?
Sympathetic
What nerve activity is mydriasis responding to?
primary, secondary, and tertiary structure; quaternary
What proteins have a single polypeptide chain? Multiple polypeptide chains?
membrane proteins
What surface do nonpolar amino acids cluster on?
soluble proteins
What surface do polar amino acids cluster on?
maximum buffering capacity occurs at a pH equal to pKa
When does maximum buffering capacity occur?
glomeruli
Where are weakly acidic and basic drugs filtered for excretion?
lens
Which ocular structure continues to grow in both thickness and diameter throughout our lifetime?
hydroxylation (adding -OH to residual groups increases crosslinking and H bonding) => collagen and anti oxidant effects
Why should you up vitamin C intake with severe corneal abrasion/ulcer/surgery?
negative allosteric effectors or allosteric inhibitors - increase pCO2 - increase temp - decrease pH - increase 2,3-BPG ex: decrease in pH results in decreased oxygen affinity of hemoglobin and therefore a shift to the right in the oxygen-dissociation curve
Why would there be a rightward shift in hemoglobin curves?
5.270 = 4.752 + log (x/10) log(x/10) = 0.518 x/10 = 3.296 x = 33.0 mmol of sodium acetate
You need to produce a buffer solution that has a pH of 5.270. You already have a solution that contains 10.0 mmol (millimoles) of acetic acid. How many millimoles of sodium acetate will you need to add to this solution? The pKa of acetic acid is 4.752.
Acidic urine Weak basic => excreted more rapidly
Your patient takes high quantities of ascorbic acid (vit C) supplements, causing acidification of the urine. How will this affect the retention of the weakly basic drug diazepam?
endothelial
__________ cells play a major role in limiting fluid uptake
weakly basic
____________________ drugs are excreted more rapidly in acidic urine and less rapidly in alkaline urine
weakly acidic
____________________ drugs are excreted more rapidly in alkaline urine and less rapidly in acidic urine
oligopeptide
a few amino acids joined together
protein
a macromolecule that consists of one or more polypeptide chains; typically considered 50 amino acids or greater
presbyopia
advancing age = the lens becomes denser and less elastic; as a result the ability to accommodate is lessened
trans peptide bond
alpha carbons on opposite sides. Lower energy(more favored)
amphoteric molecules
amino acids in solution function as weak acids/weak bases
essential amino acid
an amino acid that must be obtained through diet; it cannot be synthesized from other precursors
accommodation
an increase in refractive power of the eye through a change in lens shape; ciliary muscle contraction
lens epihelium
anterior surface only
molecular chaperones
bind reversibly to unfolded polypeptide segments and prevent misfolding and premature aggregation; ATP hydrolysis
connective tissue
bind tissues together and provide support for the organs and other structures of the body
caspases
break down cells as lens matures
chiral center
carbon with four different substituents and lack a plane of symmetry; alpha carbons have this
accommodated
ciliary muscle contracts and les tension in zonules (relaxed and curl)
unaccommodated
ciliary muscle relaxed and zonules have tension
fibrous components
collagen and elastin
alpha amino acids
common amino acids (20 standard) are known as:
ciliary body
complete ring that surrounds the lens
strong electrolytes
completely dissociate in solution
amino acid
compound consisting of a carbon atom to which there are attached a primary amino group (-NH2), a carboxyl group (-COOH), a side chain (R group), and an H atom
pKa
constant for each type of molecule
iris
controls the amount of light entering the eye by controlling pupil size
hemoglobin sigmoidal curve; permits the blood to deliver much more O2 to the tissues than if hemoglobin had a hyperbolic curve
cooperative interaction between binding sites; O2 binding to one site increases the O2 affinity of the remaining subunits
proteoglycan
core protein to which at least one glycosaminoglycan chain is covalently attached; hydrated network resists compression and provides pressure to maintain volume; major component of connective tissue
collagen type I
corneal stroma
peptide bond
covalent bond (amide linkage) between the amino group of one amino acid and the carboxylate group of another; dehydration synthesis
Henderson-Hasselbalch equation
demonstrates the relationship between the pH of a solution and the concentration of a weak acid (HA) and its conjugate base (A-); allows us to predict the relative amounts of protonated and unprotonated species in solution
sclera
dense connective tissue layer lined by a thin mucous membrane (conjunctiva); OPAQUE due to irregularly-spaced collagen fibrils
fovea centralis
depressed area within the center of the macula; highest concentration of cones and provides the most distinct vision
nonelectrolytes
dissolve as molecules in solution and do not break into ions
elastic capsule
envelopes the entire lens
scaffold
fibrillin + elastin
cellular components
fibroblasts ex: keratocytes (stroma of cornea)
elastin
fibrous, insoluble protein, present with collagen in the connective tissues; highly branched, amorphous structure responsible for physical elasticity
anterior chamber
filled with aqueous humor appears optically empty and black
vitreous body
gel-like substance filling the eyeball between the lens and the retina
ground substance
glycosaminoglycans, proteoglycans, glycoproteins
myoglobin
heme protein found in heart and skeletal muscle; O2 carrying protein that binds and releases O2 with changes in the O2 concentration; oxygen reservoir; high O2 affinity and only gives up O2 when pO2 drops low
strong acid
higher Ka, lower pKa; greater tendency to "give up" its proton
zonules
hold the lens in place; delicate, radially arranged fibers
miosis (constriction)
in bright light and accommodation
mydriasis (dilation)
in low-intensity light and during excitement or fear
positive allosteric effectors or allosteric activators ex: oxygen and carbon monoxide - carbon monoxide competes with oxygen binding sites and has a higher affinity than oxygen
increase the affinity of hemoglobin for oxygen, cause a leftward shift in the O2 binding curve - increase R-state stability and decrease T state (deoxy) stability
collagen type III
iris
mostly products
large K (more than 10^3) is a strong acid so will have =
collagen type IV
lens capsule (surrounds lens) and Descemet's membrane (thin layer of cornea)
glycosaminoglycans (GAGs
long, unbranched polysaccharides making up the ground substance; highly hydrophilic (neg charge)
collagen fibers collagen molecule -> collagen fibril -> collagen fibers
made up of many collagen fibrils; covalent cross links
lens fibers
main mass of the lens
Fibrous proteins
mainly one kind of 2* structure
polypeptide
many amino acids joined together (usually 4 or more)
globular proteins
mixed 2* (secondary) structure alpha and beta
zwitterion (dipolar ions)
molecules which bear plus and minus charges simultaneously
protein
most abundant/functionally diverse molecules in the body
cornea
most important refractive medium in the eye
conjunctiva
mucus membrane that covers sclera and eyelids
allosteric protein ex: hemoglobin
multiple ligan binding sites; binding at one site affects binding at another (cooperative binding)
hyperbolic O2 binding curve
myoglobin binding curve that rises quickly and plateaus at top
proteases
name the enzyme that is present in the body that can aid in peptide degradation
anion
negatively charged ion
antiparallel
neighboring H-bonded polypeptide chains run in opposite directions C<-N C->N
parallel
neighboring H-bonded polypeptide chains run in the same direction C->N C->N
retina
nervous coat, internal layer of the eyeball; thin, transparent membrane; photochemical transduction
unionized
no charge but uneven electron distribution
prosthetic group
non-protein molecule that is vital to protein function
choroid
nourish the outer layers of the retina and absorb excess light
cataract
opacification/yellowing of the lens
macula lutea
oval, darkened area of the central retina
Henderson-Hasselbalch equation
pH = pKa + log [A-]/[HA]
respiratory acidosis
pH<7.35, obstructive lung disease isa type of _____________ that prevents efficient expiration of CO2 from the lungs
metabolic alkalosis
pH> 7.45, kidney disease with bicarbonate retention would be ___________________
weak electrolytes
partially dissociate in solution
acidic ex: COO-
polar negatively charged
basic ex: NH3+
polar positively charged
globular proteins
polypeptide chains folded into spherical or globular shape; often multiple secondary structures; water soluble
cation
positively charged ion
denaturation
protein alteration from its native form; unfolding and disorganization of a protein's secondary, tertiary, and quaternary structures WITHOUT the hydrolysis of peptide bond; may be reversible ex: heat, detergents, strong acids/bases
fibrous protein
proteins characterized by polypeptide chains in a stiff, elongated strand or sheet, that tend to form fibers; resist stretching and provide shape and tensile strength; insoluble; large amounts of secondary structure ex: keratin, collagen, elastin
secondary structure ("local folding")
recurrent structural patterns of the polypeptide backbone; arise from repeated hydrogen bonding within a chain
Bohr effect - negative allosteric effectors influence binding
reduction in oxygen binding with lowered pH (increased [H+]) or increased pCO2; both stabilize the T state
heme
site for reversible oxygen binding
optic nerve/optic disc
site where axons of retinal nerve cells accumulate to exit the eye (pass through opening in sclera); site where retinal blood vessels enter the eye; light pink/orange color
mostly reactants
small K (less than 10^-3) is a weak acid so will have =
buffers
solutions that resist a change in pH when acids or bases are added
quaternary structure
spatial arrangement of a macromolecule's individual subunits
electrolytes
substances that dissociate in water into cations and anions
collagen fibrils
supramolecules made up of triple-helix collagen molecules
ciliary body
suspension of the lens and process of accommodation (site of zonule origination); produce aqueous humor
hemoglobin
tetrameric protein with a a2B2 quaternary structure; 4 subunits each containing a heme prosthetic group (porphyrin ring with Fe2+)
amino terminus (N-terminus)
the "beginning" of an amino acid chain, contains NH2 group
carboxyl terminus (C-terminus)
the free carboxyl group at one end of a polypeptide
pKa
the negative logarithm of the dissociation constant of an acid
an amino acid sequence in a triplet repeat
the structure of collagen involves:
choroid
thin lining along the inner surface of the sclera; continuous with ciliary body anteriorly; highly vascular and pigmented layer
standard amino acids
those for which at least one codon exists in the genetic code
tertiary structure
three-dimensional shape of a polypeptide due to domains (interactions of the R groups) of the amino acids making up the chain; maintained by stabilizing interactions of the side chains: ionic bridges, hydrogen bonds, disulfide bonds, and hydrophobic interactions
lens
transparent, biconvex structure located within the posterior chamber; grows throughout life in diameter and thickness
Vuity
treatment of presbyopia in adults (pilocarpine HCl ophthalmic solution) Stored at pH of 4 pKa of pilocarpine = 6.6 pH < pKa => protonated (uncharged) Want the uncharged condition so that they can easily be absorbed by the cornea
False
true or false: protein denaturation rarely occurs within cells due to the strength of peptide bonds
cis peptide bond
two alpha carbons are on the same side of the bond
stroma
uniform spacing of collagen fibrils in __________
alpha helix
very stable, R-groups are outside of the helix, C=O and N-H residues are hydrogen bonded to each other 4 residues apart ex: keratin
collagen type II
vitreous
CO2
what is the major metabolic product from the oxidation of ingested sugars?
photochemical transduction
where optical image is formed from incoming focused light; nerve impulses are created and transmitted along visual pathways to the brain
