SI and M/C - biochem 1

what is cooperativity? How does it play a role in HB and MB

- binding of one O2 induces conformational change to allow Hb to bind to 3 other oxygen molecules. converts from T-R and how subunits interact - does not play a role in myoglobin

Normal pka of strong acids

-2 higher pkA is a weaker acid (lower dissociation)

what are sialic acids? importance? relation to sars-cov-2?

9 carbon sugars that act as receptors found at terminal ends of N or O glycoproteins and glycolipids show protein age (older ones lose sialic acid) COVID binds to sialic acid (first recognized thing by spike protein)

Proteins can be separated by charge differences, through a gel-like substance. If normal HbA and sickle cell hemoglobin (HbS) are placed on such a gel, which molecule will migrate more rapidly to the positive pole of the gel? a. HbA b. HbS c. Both would have the same charge, so there is no difference in migration

A

Under appropriate conditions, Hb dissociates into its 4 subunits. the isolated subunits binds oxygen, but the O2-saturation curve is hyperbolic rather than sigmoidal. In addition, the binding of oxygen to the isolated subunit is not affected by the presence of H+, Co2, or 23BPG. what do these observations indicate about the source of cooperativity in Hb? a. arises from interaction between subunits b. cooperative behavior - sigmoidal O2 binding curve and the positive cooperativity in ligand binding - is initiated by the binding of O2 to the heme group c. H+, CO2, 23BPG interact independently with each other D. Hb cooperatively originates as a result of HbF mutations

A

Which is most likely location and amino acids found for reverse turn of beta strand? a. surface of proteins with proline and glycine b. surface of proteins with 2 cysteines c. inside proteins with 2 glutamic acids d. inside proteins with 2 cysteines.

A

Which peptide sequence is most likely found in a transmembrane helix of a protein? A) Ala-Ile-Phe-Val-Leu B) Ala-Thr-Lys-Asn-Leu C) Lys-Thr-Arg-Asn-His D) Val-Thr-Pro-Tyr-Ser

A

Describe structure of heme

A porphyrin (protoporphyrin IX) with iron at its center

Compare aldose and ketose

Aldose - aldehyde anomeric carbon is C1 Ketose - ketone, anomeric carbon is C2

A patient presents to the Emergency Department with shortness of breath, chronic cough, and fatigue. A diagnosis of acute respiratory acidosis is made. Blood pH is significantly lower (about 0.3 pH units) than normal. Individuals which this condition exhibit reduced oxygen binding to hemoglobin due to which one of the following? A. change in red blood cell pH results in the protonation of 2,3 bisphosphoglycerate, reducing its affinity for hemoglobin. b. The imidazole group of H146 from the ß-chain becomes protonated due to the altered pH, leading to stabilization of the deoxy form of hemoglobin c. The oxygen saturation curve of hemoglobin shifts to the left due to the altered pH in the red blood cell d. The reduced red blood cell pH alters the conformation of the distal histidine of hemoglobin, making it more difficult for oxygen to bind. E.The side chain of D94 of the ß-chain becomes protonated due to altered pH, leading to stabilization of the deoxy form of hemoglobin

B

A pharm company is trying to develop a drug that improves tissue oxygenation by increasing the percentage of oxygen that is released rom Hb during its passage through the capillaries of extrapulmonary tissues. It is hoped this drugs will become a popular doping agent for athletes. they should try a drug that a. binds to heme iron b. inhibits degradation of 23BPG, increasing concentration in eryththrocytes C. binds to ion channels in RBC, raising pH D. induces the synthesis of Hb y-chain in adults

B

Allie's friend Ian, engages allie in a discussion about mg and Hb. Ian asserts confidently that helix a and B or Mb are enriched in proline residues. Allie has no knowledge of the amino acid sequence but believes strongly that this clain can't be true. using what you know about protein structures who is correct and why a. ian, proline is very stable molecule often found in alpha helices b. allie, proline's rigid structure results in formation of kinks in helix disrupting the structure c. allie, proline is good residue for H-bonding but rigid ring structure makes it bad for helices d. neither, proline is never found in secondary structure

B

The oxygen binding curve of Hb is sigmoidal because a. binding of O2 to heme increases oxygen affinities of other heme groups b. heme groups of alpha chains have a higher oxygen affinity than do the heme groups of the beta-chains c. distal his allows Hb to change conformation in response to an elevated carbon dioxide concentration d. subunits helped in place by interchain disulfide bonds solubility of Hb depends changes with oxygen states

B

what level of secondary structure is increased in prion diseases? why is this a problem?

Beta sheets - insoluble when they form amyloid cross beta structure.

Proteins kinases are a class of transferases enzymes enzyme that can transfer a phosphate group from ATP to which of the following amino acids? A. N Q B. S T K C. S T Y D. W and Q E. Y and R

C

What level of protein structure is lost when a protein denatures 1. primary 2. secondary 3. tertiary 4. quaternary A. I only B. I and II only C. II, III, IV only D. All of the above

C

Sterochemical designators alpha and beta distinguish between A. enantiomers at epimeric carbon atom B. enantiomers at anomeric carbon atom C. Anomers at anomeric carbon atom D. Anomers at non-anomeric carbon atom

C. anomers at anomeric carbon atom

what is the difference between oxygen and carbon monoxide binging to heme iron? what is the problem with how CO binds? how to fix?

CO binds linearly and much better than O2. To fix, distal HE7 creates steric to prevent binding. When CO binds bet, it weakens conformation

Carbon monoxide is toxic to humans because A. binds to myoglobin and causes denaturation B. rapidly converts to toxic CO2 C. binds of globin portion of Hb and prevents binding of O2 D. binds to Fe in Hb and prevents binding of O2 E. binds to heme of Hb and causes heme to unbind from Hb

D

prions are infections proteins and can be described by which a. encoded by viruses b. exist in alternative tertiary structures c. cleave DNA at specific sites D. cleave proteins to cause function to be altered E. protect disulfide bonds from being oxidized by reducing agents

D

scientists performing site-direct mutagenesis studies on the beta chain of adult hemoglobin. they isolated an H146R mutant and characterized its oxygen binding properties. which of the following best describes the oxygen binding properties of the mutant Hb compared to adult Hb? a. mutation increases oxygen affinity in the lungs b. shifts the pH vs. oxygen binding curve of the mutant Hb to the left of adult Hb c. stabilizes R form d. stabilizes T form e. weakens BPG binding to Hb

D

which one of the following would best describe effect of G83K mutation in allosteric binding pocket for 23BPG on HbA a. decrease ease of oxygen transfer from HbA to HbF b. increase affinity of CO to heme iron c. increase proportion of R state HbA molecules d. mutation would increase proprotion T state HbA molecules

D

compare d-glyceraldehyde and L-gylceraldehyde

D: OH on the right of C1 L: OH on the left

weak acids/bases

Dissociate partially in water. HF, NH3

A fetus does not breathe inside the womb, and so it must obtain oxygen a different way. What property of hemoglobin allows a fetus to receive the oxygen it needs to develop? a. The partial pressure of oxygen in the fetus is always higher than that of its mother. b. The partial pressure of oxygen in the fetus is always the same as that of its mother. c. Fetal hemoglobin is composed of four subunits while adult hemoglobin is composed of two. d. Fetal hemoglobin has a lower affinity for oxygen than adult hemoglobin e. Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin.

E

When hemoglobin saturates with oxygen, an apparent decrease in affinity to 2,3-BPG is observed. This decrease in affinity is directly caused by: a. The alteration in charges at the 2,3-BPG binding pocket between the 2 alpha groups b. The alteration in charges at the 2,3-BPG binding pocket between the 2 beta groups c. The pH dependence of His146 d. Rupturing of the salt bridge between the His146 and the epsilon amino group e. The occlusion of the 2,3-BPG binding pocket.

E

Which factors contribute to the Bohr Effect? a. Low pH, low CO2 b. Low pH, high CO2, low temperature c. High pH, low CO2 d. Low pH, high CO2 e. Low pH, high CO2, high temperature

E

The henderson-Hasselbach equation A. allows graphic determination of concentration of acid and conjugate base from ph and acid alone B. allows graphic determination of concentration of acid and conjugate base from the pK of the acid alone C. allows graphic determination of pKa of strong acid from pH alone D. allows graphic determination of PK of weak acid from pH alone E. releases pH of a solution to the pK and the concentration of acid and conjugate base

E.

what mutation leads to sickle cell anemia? why does this happen?

E6V - replace 6th glutamic acid with valine -> hydrophobic patch on surface of deoxyHb causes aggregation of hydrophobic interactions -> distorts shape of RBC

True or False: Enzymes are changed or consumed during a reaction

False

True/false: entropy favors folded state

False - more disorder when folded.

effect of mutation in Hb: G25W

Hb has wrong shape, O2 can't bind due to the wrong structure, lose interaction between B and E helix

what is difference in adult and fetal hemoglobin? why important?

HbF has 2 alpha and 2 gamma, his143 becomes serine in Hbf. R state is stabilized since 23BPG can't bind as tightly

oxygen saturation curve for Mb, HbA, HbF

HbF has higher affinity than HbA but lower than Mb

General acid dissociation equation and henderson hasselbach equation

Ka=[(A-)(H+)]/(HA)

what are the two components of Van der Waals interactions

London dispersion (attractive) and steric repulsion (repulsive)

what is difference between forming N and O linked glycoproteins (terms of whats being transferred)

O-linked: add sugar one at a time N-linked: core oligosaccharide is transferred to Asn in a peptide chain, gets sugars added using nucleotide sugars. It reaches the core structure and all is transferred to Asn

what is the difference in T and R

T=tense, low affinity for O2 (deoxygenated, lots of electrostatic interactions present) R=relaxed , high affinity for O2- oxygenated, less interactions

T/F: These interactions are universal and are founded between any two atoms near each other

True

True or False: Enzymes are sensitive to temperature and pH

True

True or False: Enzymes are stereospecific

True

True or False: Enzymes can alter equilibrium

True

True or False: Enzymes increase the rate of reactions

True

True or False: enzymes can change an energetically unfavorable reaction into a favorable one.

True

True or False: enzymes reduce activation energy and stabilize the transition state16.

True

What is 23BPG and why is it important

What: small byproduct of glycolysis with a 5(-) charge that binds through electrostatic interaction with positively charged residues in two beta subunits in T-state stabilizes T-state

how are R groups positioned on an alpha helix and beta sheet

alpha helix: all on the outside, not good for bulky R groups beta sheets: r groups alternate, better for bulky R groups

compare alpha D-glucose with Beta-D-glucose

alpha: OH points down on C1 beta: OH points up

which component of van der waals dominates at further distances

attractive forces

describe function of residue in Hb: val98

backbone carbonyl hydrogen bond with tyr 145/side chain steric interaction with porphryin ring

Between what two amino acids region does a peptide bond form? what kind of reaction?

between the Nh2 and C=O dehydration reaction

Explain mutation: G35F

both nonpolar but large steric differences

effect of mutation in Hb:V98T

can still bind to backbone, no prob

effect of mutation in Hb: H92L

can't bind to iron so iron can't bind to O2, Hb can't work.

describe function of residue in Hb: his146

carboxyl group forms salt link with lys40 from alpha chain

describe function of residue in Hb: asp94

carboxylate group forms salt link with his146 imidizaole

similarities between hemoglobin and myoglobin

carry o2, similar globin pocket strucutre, invlude heme, distal E7, proximal F8 His

hemoglobin

carry oxygen from lung to tissue, quaternary structure of 2 alpha and 2 beta with allosteric regulation, transports co2 and H+ and cooperative binding. his63 is distal and his 92 is proximal

describe function of residue in Hb: gly25

close association with B/E helices

strong acids/bases

completely dissociate in water ex: Hcl, NaOH, KOH

what are major players in cooperative oxygen binding? which state do they shift to?

concentration of O2, CO2, pH (H+), and 2,3-BPG. shift to T

what is the key event in pathogenesis of a prion disease

conformational change in prion protein

define hydrogen bonds and why they are so important in water and molecules

definition: bonds between H with FON - strongest in lnear form between 2 electronegative atom function: protein structure and function, cohesion, adhesion, DNA and sugar structure and function, binding of substrates to enzymes

Define glycosylation and the two types and amino acids involved

definition: carbs covalently added to molecule (lipid or protein) O-linked: involve Ser, Thr N-linked: Asn

describe function of residue in Hb: His63

distal histidine, lowers linear bonding to CO

compare enantiomer and diasteromer

enantiomer: mirror image with same chemical and physical properties disteromer: non mirror image where substituent groups on one carbon are switched with different chemical and physical proeprties

compare epimer and anomer

epimer: different configuration around one specific atom anomer: stereoisomers that differ at C1

Why are van der Waals interactions important?

exist between all molecules and provide stability, stabilizes macromolecules, steric complmentaryity, binds polarizable ligands

what is the difference between ferrous and ferric iron? w

ferrous (+2) - binds to oxygen , less oxidized ferric (+3), can't bind to oxygen, more oxidized

What is the importance of chaperone proteins and what types of amino acids do they tend to bind to? why?

function: help proteins fold bind to nascent (emerging) polypeptides and stabilize by binding to their hydrophobic residues, preventing aggregation and interfering with folding

Explain mutation: E10K

goes from negative charge to positive, K much larger than E, will affect interactions

describe effect co2 has on oxygen binding

histidines can be protonated - shifting to T state. lowers the pH. CO2 produced in existing tissue

describe function of residue in Hb: tyr145

hydroxyl group forms H-bond with the backbone of val98 carbonyl

what types of protein interactions can intermolecular and intramolecular contacts lead to

intra- protein folding inter- fibrils/aggregation

Explain mutation: D9E

likely no change, both acidic and same size

effect of mutation in Hb: Y145A

lose H-bond with val98, switch to R-state, cooperativity lost, so other subunits can't interact and oxygen can bind easily

describe effect pH has on oxygen binding? what residue of Hb plays an important role in this

lowers the pH, increases H+, decreasing oxygens affinity of Hb. His146 plays a role. lower pH leads to easier protonation of His146 imidizaole side-chain and the R to T transition and salt bridge forms with Asp94 - effect on BPG binding: low pH high H+, protonating His residues favoring 23BPG

How does cholesterol affect membrane fluidity

makes it more rigid, helps with membrane stability

dielectric constant definition what molecules do they play a role in

measure of electrical conductivity - shows what molecules (polar/nonpolar) are solvated in the solvent micells lipid behavior amino acids and general protein structure

Buffer function and molecules they act on

minimize pH change when H or OH is added. act on weak acids and conjugate bases

what happens in the body at high altitudes and why?

more 23BPG = stabilize T state and more O2 is released to the tissues. Since there is less oxygen present, we breathe more so there is more BPG (increased heart rate) and more Hb in T state causing O2 to be released

Explain mutation: I3L

no change, size and charge both nonpolar

effect of mutation in Hb: D94E

no problem, salt link forms

how does entropy of water change when hydrophobic groups are clumped or not

non clumped: increase entropy of proteins and decrease for water. Water is more ordered because it has to arrange themselves around each lipid. clumped: water is dispersed and less water is used to surround the hydrophobic groups so water entropy increases.

what happens at midpoint of titration? pkA effect?

pKa= ph at which 50% dissociation occurs

four levels of protein structure and the type of bonds in between them

primary - linear order of amino acids secondary: local folded structures that form in a polypeptide chain due to repeating patterns of H bonds between atoms in a backbone tertiary: folding of 2ndary structures into unique 3D shapes, disulfide bridges, hydrophobic interactions, salt bridges, H-bonds and Van der waals Quaternary: 2+ polypeptide chains with same bonds as tertiary structure. not present in all proteins

What role does proline serve in secondary structure

proline is rigid and causes kinks, seen at start of helic and beta turns

describe function of residue in Hb: his92

proximal his, forms coordinate covalent bond at 5th position with iron

compare pyranose and furanose

pyranose - 6 carbon ring furanose - 5 carbon ring

list the oxidation state, 5th and 6th coordination position of deoxymyoglobin, oxymyoglobin, ferrimyoglobin

refer to chart in SI worksheet 3

effect of mutation in Hb:H146R

salt bridge can form but never break and let go of o2, always in T state

effect of mutation in Hb:H146C

salt bridge doesn't form. no cooperative, no communication, R state is stabilized bc no interactions

difference between saturated and unsaturated fatty acids

saturateD: no double bonds, solid at room temp unsaturateD: at least 1 double bond, liquid at room temp

how are enzymes able to lower free energy of activation

stabilize transition state through binding energy binding energy is initial binding of substrate to enzyme that stabilizes TS by distorting substrate to the TS. - substrate binds leads to conformational change at active site substrate starts to look like product lowering Ea

myoglobin

stores oxygen in muscle for times of O2 deprivation, monomeric protein with heme, higher affinity for oxygen, binding is noncoperative, O2 affinity independent of pH, co2 etc/ his 93 - distal and his 64 - proximal

list five types of lipids and functions

triacylglycerols: energy storage phospholipids: membrane lipids bile acids: emulsification steroid hormones: messenger kipids biological waxes: protective coating

true/false: folded state of the protein is only marginally stable

true