biochem 1.pptx

7/25/2019 Biochem 1.pptx

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What is an AA?

What is a proteinogenic AA?

What is a -carbon and what is it bonded to inan AA?


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An AA is a molecule that contains: NH2(amino) and CH

(carbo!"l)#

NH2and CH don$t ha%e to be bonded to the same C#

Not e%er" AA in the bod" is speci&ed b" a codon in thegenetic code or incorporated into proteins#

'ome AAs are speci&call" modi&ed or specialied roles inthe bod"#

*roteinogeneic Amino Acid: 2+ -AAs encoded b" the humangenetic code#

-carbon is the carbon adjacentto the carbo!"l carbon#

,onded to it in -AAs are H . (side chain) CH / NH2


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AA 'tereochemist"


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0!cept or gl"cine all AAs are chiral (stereogenic)#

most o them opticall" acti%e#

All chiral AAs used in eu1ar"otes are -AAs#

amino will be drawn on let in a 3ischer pro4ection

All AAs but c"steine are in an ' con&guration#

C"steine while still an -AA has an . con&gurationbecause the CH2'H group has priorit" o%er CH#


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ist or the nonpolar nonaromatic side chainAAs:

'tructure

Names5 letter abbre%iation6 letter abbre%iation


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77l"

'mallest#Achiral#

88et

ne o the twoAAs containing

With meth"l

attachedrelati%el"nonpolar#

**ro

C"clic AA#Constrains 9e!ibilit" limitingoptions or placement andsig# eecting proline$s rolein 2; structure#

AAla

"r.elati%el" polar


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ist or the polar side chains side chain AAs:'tructure



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''er

Highl" polar#Can do H-,onding#

>>hr

Highl" polar#Can do H-

,onding#

NAsn

Amide (.)doesn$tgainloose pBwith changes inpH#

7lnAmide (.)doesn$tgainloose pBwith changes inpH#C

C"sHas a thiol('H) group#'H bond wea1er than H prone to o!idation#


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ist or the negati%el" charged (acidic) sidechains side chain AAs:

'tructure



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Negati%e charges atph"siological pH (D#E)

FAsp

07lu


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ist or the positi%el" charged (basic) sidechains side chain AAs:

'tructure



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B charge delocalied o%er 5N atoms#

H

His.ing G imidazoleAt ph"siologic pH one N is protonated#Acidic conditions both Ns areprotonated#

"s

.Arg


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Comment on our abilit" to classi" AAs as

h"drophobic or h"drophilic#


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Classi"ing Aas G comple!#

e!: t"rosine has both an H group (h"drophilic) and anaromatic ring (h"drophobic)#

'ome clear conclusions:

ong al1"l side chains are strongl" h"drophobic

8ore li1el" to be ound on inside o proteins#

Alanine isoleucine leucine %aline / phen"lalanine#

AAs with charged side chains are h"drophilic as are theamides#

Histidine arginine l"sine glutamate asparate

asparagine and glutamine# .emaining AAs are neither particularl" h"drophilic or

h"drophobic#


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AAs are amphoteric species because the" can either accept aproton or donate a proton#

=oniable groups gain protons under acidic conditions andloose them under basic ones#

pais the pH at which on a%erage I mocs are deprotonated

JHAK G JALK

pH M pamost o the species will be protonated#

pH pamost o the species will be deprotonated#

AAs ha%e at least 2 pa

%alues#

pa6or the CH usuall" 2

pa2usuall" or the NH2 usuall" O-6+


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Fescribe what happens to a generic AA at pHo 6#

Fescribe what happens to a generic AA at pHo D#E#

Fescribe what happens to a generic AA at pHo 6E#


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,oth the amino and carbo!"lic group will be protonated (NH5B

and CH)#

Charge will be positi%e because the amino group is

positi%el" charged and the carbo!"lic group is neutrall"charged#

>he carbo!"lic group will be deprotonated (CL) and theamino group with be protonated (NH5

B)#

>he ensuing molecule has a B and L charge an o%erall iselectrical neutral# We call such molecules dipolar ions orzwitterions#

Pwitterions e!ist in water as internal salts#

,oth the amino and carbo!"lic group will be deprotonated (NH2

and CL)#


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Assuming that the titration o each protonoccurs as a distinct step resembling twocombined monoprotoic acids what would

the titration cur%e loo1 li1e or a generic AAwith an uncharged side chain loo1 li1e?


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=n a 6 8 solution o the base:

When +#Q eRui%alents o base ha%e beenadded J Ko ull" protonated AA and itswitterion are eRual# >he pH G pa6#

When pH is close to its pa %alue o a solute

a solution$s acting as a buer#

Adding 6#+ eRui%alent base the AA e!istssolel" as a witterion# At this point the

pH G the isoelectric point (p=) L the pointthe moc is electricall" neutral#

At the neutral point the moc is especiall"sensiti%e to pH changes#

At 6#Q eRui%alents o base added the J K othe witterion G the ull" deprotonatedorm and the pH G pa2#

At 2#+ eRui%alents o base the AA is ull"


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How do "ou calculate the p= or a neutral AA?

How do "ou calculate the p= or an acidic AA?

How do "ou calculate the p= or a basic AA?

Comment on the relati%e p= %alues or AAs withacidic %s# basic side chains#


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Amino acids with acidic side chains ha%e p= %alues well below

S#

Amino acids with basic side chains ha%e p= %alues well abo%eS#


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Fescribe peptide bond ormation#


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0!ample o a condensationdeh"dration reaction or an ac"l substitutionreaction#

6# Nucleophilic aminogroup attac1s the

electrophilic carbon"lgroup#

2# Ater the attac1 theh"dro!"l group o thecarbo!"lic acid is1ic1ed o#

Amide has delocaliableT e-in the carbon"l andlone pair on the amino NG resonance#

CLN bond has partial

double bond characterrestricting rotation andma1ing the bac1bonemore rigid#

N-terminus C-term

inus

Note: ," con%ention peptidesare drawn and read rom N toC terminus#


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Fescribe bond h"drol"sis#


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3or en"mes to carr" out their unction peptides need to berelati%el" stable in solution# >hus the" don$t t"picall" allapart on their own#

n the other hand to digest proteins we need to brea1 themdown#

Chemicall" spea1ing amides can be h"drol"ed using acidor base catal"sts #

>his is called acid h"drol"sis#

Non-speci&c wa" o clea%ing#

=n li%ing organisms h"drol"sis is catal"ed b" h"drol"ticen"mes that clea%e at speci&c points in peptide chains

>his is called proteol"sis#

'peci&c wa" o clea%ing#

o 0!amples: tr"psin / ch"motr"psin#

o >hese brea1 the amide bond b" addition a H to the


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What is a protein and what are its generalunctions in the bod"#

What are the le%els o protein structure?

What e!actl" is the 6; structure o a protein?


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*roteins are pol"peptides ranging rom a ew to thousands oAAs#

>he" can act as: en"mes hormones membrane pores

membrane receptors cell structure elements#

e%els o structure: *rimar" 'econdar" >ertiar" / uaternar"#

*rimar" structure: the linear arrangement o AAs coded in anorganism$s FNA#

'tabilied b" the ormation o co%alent peptide bondsbetween AAs#

0ncodes all ino needed or olding all higher le%els o

structure (the protein adopts the most energeticall"a%ourable arrangement in a gi%en en%ironment)#

Can be determined with the lab techniRue sequencingL


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Fescribe a protein$s 2; structure#

Fescribe alpha helices#


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2; structure: the local structure o neighboring AAs#

*rimaril" the result o H-bonding between nearb" AAs#

>wo most common structure are -helices / V-pleated sheets#

e" to their stabilit" is the ormation o intramolecular H-bonds between dierent residues#

-helices

.od-li1e peptide chain coiling cloc1wise around a centrala!is#

'tabilied b" H bonds between carbon"l and an amide Hour residues down the chain#

'ide chains point outwards#

=mportant component o 1eratin (a &brous structuralprotein)#


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Fescribe V-pleated sheets#

Fescribe the role o proline#


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*eptide chains lie alongside each other either parallel or anti-parallel and are held together b" H-bonds#

,onds are between carbon"l and amide H on an ad4acent

chain#Assume pleatedrippled shape to accommodate as man" H-

bonds as possible#

. groups point abo%ebelow plane o the sheet#

*roline introduces a 1in1 in the peptide chain when ound inthe middle o an -heli! due to its rigid c"clic structure

.arel" ound in -heli! e!cept in helices that cross the cellmembrane#

3ound as the residue at the start o a -heli!#

.arel" ound in the middle o pleated sheets#

-


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What are the two broad di%ision o proteinsbased on 5; / E; structure?

What causes 5; / E; structure?

Comment on the chronolog" o proteinormation#

, d di i i


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,road di%ision:

3ibrous proteins that ha%e structures that resemblesheetslong strands#

7lobular proteins that tend to be spherical#

*rotein olding causes 5; / E; structure#

i1el" that 6; then 2; structures orm &rst then h"drophobicinteractions and H-bonds case the protein to collapse$#

=ntermediate states are 1nown as molten globules#

*rocess is %er" ast (much less than a second)#


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> ti t t i t i $ 5 F h


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>ertiar" structure is a protein$s 5-F shape#

8ostl" determined b" h"drophobic and h"drophilicinteractions between . groups#

H"drophobic residues hangout inside the peptide#

N-H and CG bonds in the peptide tend to be pulled tothe inside b" these h"drophobic residues H-bonding andengaging in electrostatic interactions to urther stabiliethe protein#

5-F structure can also be determined b" H-bonding / acid-base interactions (salt bridges)#

Fisul&de bonds L when two c"steine residues o!idie to ormc"stine (loosing two protons and two electrons) creating a

loop in the protein structure#>he loss o tertiar" structure is called denaturation and

results in loss o unction#

-


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When solutes dissol%e in sol%ent sol%ent mocs orm a


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When solutes dissol%e in sol%ent sol%ent mocs orm asol%ation la"er around the solute#

H"drophobic .s in aRueous solutions cause the sol%ation la"er

not to be able to orm H-bonds with it orcing the H2 torearrange itsel (meaning negati%e entrop" -X')#

>his ma1es the o%erall process nonspontaneous (X7 +)#

*utting h"drophilic residues on the e!terior allows H2 mocs

more latitude increasing their entrop" (X' +)#

>his ma1es the o%erall process spontaneous#

Also allows the protein to achie%e ma! stabilit"#


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E; structure: an aggregate o smaller globular peptides or subunits creating


42/46

E structure: an aggregate o smaller globular peptides or subunits creatingthe unctional orm o the protein#

nli1e the other le%els not all proteins ha%e this t"pe o structure#

.eRuires more than one pol"peptide chain#

0!ample: hemoglobin Has E subunits each binding to one moc o L 2 subunits and 2V

subunits#

0!ample: immunoglobin 7 (=g7) Has E subunits#

ses all t"pes o bonds: %an der Waals H-bonds ionic bonds co%alentbonds#

.oles ser%ed:6# ,ecome more stable b" reducing surace area o protein comple!#

2# .educe amount o FNA needed to encode the protein comple!#

5# ,ring catal"tic sites close together allowing intermediate rom onreactions to be shuttled o to a second one#

E# Can induce cooperati%it" or allosteric eects L one subunit


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Fescribe con4ugated proteins#


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45/46

Fescribe the denaturation o proteins#

Fenaturation: protein loses its 5-F structure#


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Fenaturation: protein loses its 5 F structure#

ten irre%ersible#

nolded proteins can$t catal"e reactions#

>wo main causes:

Heat L 1inetic energ" ma" o%ercome h"drophobicinteractions holding a protein together#

'olutes L intereres directl" with the orces that holdproteins together L 2; 5; / E;)#

biochem 1.pptx

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