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