生物化学-课件lecaminoacids

氨基酸、多肽、蛋白质The

light

produced

byfireflies

is

the

resultof

areaction

involvingtheprotein

luciferin

andATP,catalyzed

bythe

enzymeluciferase.Erythrocytes

containlarge

amounts

of

theoxygen‐transportingproteinhemoglobin.Theprotein

keratin,formed

by

all

vertebrates,is

thechief

structuralcomponent

of

hair,

scales,horn,

wool,

nails,

andfeathers.2分布广：所有、组织都含有蛋白质；细胞的各个部分都含有蛋白质。含量高：蛋白质是细胞内最丰富的有机分子，占

干重的45％，某些组织含量更高，例如脾、肺及横纹肌等高达80％。蛋白质具有重要的生物学功能：作为生物催化剂（酶）代谢调节作用免疫保护作用物质的转运和运动与支持作用参与细胞间信息传递。。。。。。1.

Biology

catalytic

activity—Enzymes3a. To

regulate

the

ability

of

other

proteinshormones:insulin(胰岛素)somatotropin(生长激素)

thyrotropin(促甲状腺素）b.

To

regulate

t e

expressionpositively:

AP1negatively:

NF1lac

repressor (乳糖抑制体)2.

Biological

Regulation

Activity—Regulatory

proteins4Lac

repressor

DNA‐binding(Helix‐turn‐helix

motif)AP‐1

bound

to

a

DNA

oligomer(Leucine

zipper

motif)5Lac

repressor

inhibits

the

expression

ofgenes

coding

for

proteins

involved

in

themetabolism

of

lactose

in

bacteria.AP‐1

upregulates

transcription

of

genescontaining

the

TPA

DNA

response

element3.

Transport

Function—Transport

ProteinsTransport

within

or

between

different

cells

or

tissuesTransport

into

or

out

of

cellsHemoglobin6Membrane

Transport

ProteinStorage

proteins

serve

as

reservesof

metal

ions

and

amino

acidsovalbumin

（卵清白蛋白）caseinzeinferritin（酪蛋白）（玉米蛋白）（铁蛋白）4.

Storage

Function—Storage

ProteinsCasein

micelle

in

milk

(82%)Zein

is

the

storage

protein

in

cornkernels.Ferritin

molecules

store

thousands

ofiron

atoms

within

their

mineral

core7Motor

proteinkinesin

(驱动蛋白）Contractile

and

Motile

Proteinsactin

（肌动蛋白）myosin（肌球蛋白）tubulin

（微管蛋白）5.

Motor

FunctionMotor

protein‐dependentmovement

of

cargo.8Structure

of

skeletal

muscle.collagen

（胶原蛋白）elastin

（弹性蛋白）keratin

（角蛋白）9fibroin（蚕丝蛋白）proteoglycan

（蛋白聚糖）6.

Structural

component

—Structural

ProteinsA

kind

of

proteins

involving

in

the

complex

pathways

ofcellular

response

to

hormones

and

growth

factors:

IRS‐1(insulin

receptor

substrate

)Anchoring

proteins

:

AKAP

(a

kinase

anchoring

proteins)7.

Scaffold

Function

—Scaffold

Proteins

(

Adaptor

proteins)The

intramolecularphosphorylation

of

the

AKAPof

AKAP250inresponse

to

and

mediated

bythe

association

with

β2AR10霍华德∙休斯医学研究员，杜克大学医学中心生物化学教授罗伯特∙科维茨（1943）和 斯坦福大学医学院医学教授以及分子和细胞生物学教授布莱恩∙克比尔卡（1955）因在“G蛋白偶联受体（GPCRs）”方面所作出的突破性贡献而被授予2012年度 化学奖。罗伯特∙科维茨布莱恩∙克比尔卡11GproteinCoupledReceptors~200

functional

assigned

receptors~600

functionally

unassigned

receptors

(Orphan

Receptors)Hundreds

sensory

and

hormone

receptorsAccounting

for

nearly

60%

of

all

prescription

drugs

on

the

market

todayincluding

12

of

the

top

20

drugs12immunoglobulins

（免疫球蛋白）blood‐clotting

proteinsthrombin（凝血酶）fibrinogen

（纤维蛋白原）antifreeze

protein

（抗冻蛋白）lytic

and

neurotoxic

proteinssnake

and

bee

venoms

（毒液）ricin(蓖麻毒素）diphtheria

（白喉毒素）8.

Protective

and

attack

–Protective

and

Exploitive

Proteins13Proteins

are

linear

polymers

of

20

different

amino

acidsThey

are

the

embodiment

of

the

transition

from

one-dimensional

world

of

sequences

to

the

three

dimensionalworld

of

molecules

capable

of

diverse

activities.蛋白质的结构和功能DNA

replication

machinery

can

make

DNA

copy

without

dissociation1420种氨基酸赋予了聚合物蛋白质特异的功能和性质蛋白质与其他大分子的相互作用蛋白质功能的灵活性A

complex

protein

assembly.A

hexagonal

array

of

twokinds

of

protein

filaments15Upon

binding

iron,

the

protein

lactoferrinundergoes

conformational

changes蛋白质的结构和功能Chains

of

amino

acids

in

a

specific

sequence

(primary

structure)

define

aprotein

like

insulin.

These

chains

fold

into

well-defined

structures

(tertiarystructure).

Such

structures

assemble

with

other

chains

to

form

arrays

suchas

the

complex

of

six

insulin

molecules

(quarternary

structure).从一级结构到四级结构16蛋白质的结构和功能The

functions

of

proteinarise

from

specific

bindinginteractions

andconformationalchanges

in

the

structure

ofa

properly

folded

protein.17Protein

are

built

from

a

repertoireof

20

aminoacids每个α-氨基酸含有连接于同一个碳原子的一个羧基、一个氨基和一个氢原子，以及结构、大小和带电性不同的侧链或称R基团。氨基酸18With

four

different

groupsconnected

to

the

tetrahedral

α-carbonatom,

α-amino

acids

are

Chiral:

two

mirror

image

forms

are

calledL

isomer

and

D

isomer.α-氨基酸可以是一对

异构体(stereoisomers)19Only

L

isomer

are

found

in

proteins.

All

L

amino

acids

havean

absolute

S

(rather

than

R)

configuration.

The

counterclockwisedirection

from

the

highest

to

lowest

substituents2021The

remarkable

range

of

functions

mediates

by

proteins

resultsfrom

the

diversity

and

versatility

of

20

amino

acids氨基酸的分类和结构1根据氨基酸的化学结构分为：脂肪族，芳香族和杂环族三类。2根据氨基酸的R基极性分为：非极性R基氨基酸，不带电荷极性氨基酸，带电荷极性氨基酸3根据氨基酸分子中所含氨基和羧基数目的不同分为：中性、碱性、酸性氨基酸4根据氨基酸的R基物理性质，与水的相互作用分为：疏水氨基酸，亲水氨基酸非极性脂肪族R基团(7)根据R基团分类氨基酸The

larger

aliphaticside

chains

arehydrophobic-that

is,they

tend

to

clustertogether

rather

thancontact

to

water.Hydrophobicamino

acidsGlycine

isthe

simplest,and

beingachiral.甘氨酸丙氨酸脯氨酸缬氨酸亮氨酸异亮氨酸甲硫氨酸22The

side

chain

of

proline

is

bonded

to

both

the

nitrogen

and

theα-carbon

atoms.

Proline

markedly

influences

protein

architecturebecause

its

ring

structure

makes

it

more

conformationally

restrictedthan

the

other

amino

acids脯氨酸(Proline)是一个很特别的氨基酸23芳香族R基团(3)苯丙氨酸

酪氨酸

色氨酸芳香族氨基酸聚能吸收紫外光24根据R基团分类氨基酸分子对光的吸收：Lambert-Beer定律2526色氨酸、酪氨酸的最大吸收峰在280nm

附近。大多数蛋白质含有这两种氨基酸残基，所以测定蛋白质溶液280nm的光吸收值是分析溶液中蛋白质含量的快速简便的方法。极性不带电R基团(5)Cysteine

contain

asulfhydryl/thiol

group.Asparagine

and

glutaminecontain

amidegroups.丝氨酸Serine

and

threoninecontain

hydroxyl

groups.苏氨酸半胱氨酸天冬酰胺谷氨酰胺27根据R基团分类氨基酸多肽链上的两个半胱氨酸分子或残基可以以二硫键相连（e.g.胰岛素）二硫键连接的残基有强的疏水性（非极性）二硫键在两个不同蛋白质链间或蛋白质分子内的不同部分形成共价连接，在许多蛋白质结构中扮演着重要的角色（e.g.稳定蛋白结构）28带正电（碱性）R基团(3)With

a

pKa

value

near

6,Histidine

can

binds

or

releaseprotons

near

physiological

pH.29Histidine

is

often

found

in

theactivesite.赖氨酸

精氨酸At

neutral

pH,

lysine

andarginine

are

positive

charged.组氨酸根据R基团分类氨基酸带负电（酸性）R基团(2)In

some

proteins,acidic

amino

acidsaccept

protons,

andthis

ability

is

oftenfunctionally

important.天冬氨酸

谷氨酸Aspartate

and

glutamate

are

hydrolyzedproducts

of

asparagine

and

glutamine

byacid

or

base,

respectively.30根据R基团分类氨基酸20个氨基酸的简写31Amino

acids

are

often

designated

by

either

a

three‐letterabbreviation

or

a

one‐letter

symbol20个氨基酸的简写32Amino

acids

are

often

designated

by

either

a

three‐letterabbreviation

or

a

one‐letter

symbol非标准氨基酸也有重要功能334‐羟脯氨酸5‐羟赖氨酸6‐N‐甲基赖氨酸γ‐羧基谷氨酸锁链赖氨素硒代半胱氨酸鸟氨酸瓜氨酸The

ionization

state

of

amino

acids

is

altered

by

a

change

in

pH.The

zwitterionic

form

predominates

near

physiological.34氨基酸是兼性离子(zwitterions)35当外液pH为某一pH值时，氨基酸分子中所含的-NH3+和-COO-数目正好相等，净电荷为0。这一pH值即为氨基酸的等电点，简称pI。某氨基酸的等电点即为该氨基酸两性离子两边的pK值和的一半。在氨基酸等电点以上任何pH，AA带净的负电荷，在电场中向阳极移动；在氨基酸等电点以下任何

pH，AA带净的正电荷，在电场中向阴极移动。在一定pH范围中，溶液的pH离AA等电点愈远，AA带净电荷愈多。等电点

pIpH=pI氨基酸的兼性离子+OH‐+H+pH>pIpH<pI阳离子阴离子R

CH

COOHNH2R

CH

COO-3NH

+R

CH

COO-NH2‐R

CH COOH

+OH+H+336NH

+氨基酸有特征滴定曲线(Titration

Curves)1K

[Glyo

][H

][Gly

][Glyo

]K2

[Gly

][H

]

[H

]2

[Gly

]371K

K2[Gly

]At

isoelectric

point[Gly-]=[Gly+]K1·

K2=[H+]21

2[H+]=

(K

·

K

)1/2I

=

(K1·

K2)1/2pI

=

(pK1+

p

K2)/2Gly pI=(2.34+9.60)/2=

5.97缓冲区氨基与离去的质子之间的相互排斥使羧基的pKa

减小羧基中带负电荷的氧原子将电子从氨基拉过来，使氨基的pKa

减小甘氨酸离子基团的pKa

值小于那些被简单的甲基取代的氨基或羧基。这一pKa值得受扰下调是由于分子间的相互作用。电性相斥导致兼性离子不稳定，推动平衡向右进行。38394041带点状态判定pI

–

pH

<

0pI

–

pH

>

0pI

–

pH

=

0带负电带正电不带电等电点的计算侧链为非极性基团或虽为极性基团但不解离的AA：pI

=

½

(pK1

+

pK2)酸性AA(Glu,Asp,Cys)：pI=½(pK1

+pKR)碱性AA(lys,Arg,His)：pI=½(pKR

+pK2)等电点pISeven

of

the

20

aminoacids

have

readilyionizable

side

chains.421.8~2.48.8~11.0Only

histidine

has

an

Rgroup

(pKa

6.0)

providingsignificant

buffering

powernear

the

neutral

pH

usuallyfound

inthe

intracellularand

extracellular

fluids

ofmost

animals

andbacteria.多肽是氨基酸链Proteins

are

linear

polymers

by

linking

the

α-carboxyl

group

of

one

aminoacid

to

the

α-amino

group

of

another

amino

acid

with

a

peptide

bond.The

formation

of

a

dipeptide

is panied

by

the

loss

of

a

water,

andrequires

an

input

of

free

energy.

Peptide

bonds

are

quite

stable

kinetically,because

of

high

activation

energy.A

polypeptide

chain

consist

of

regularly

repeating

part,

main

chain

/backbone.

The

backbone

is

rich

in

hydrogen-bonding

potential.43肽是由氨基酸通过肽键缩合而形成的化合物。两分子氨基酸缩合形成二肽，三分子氨基酸缩合则形成三肽……由十个以内氨基酸相连而成的肽称为寡肽(oligopeptide)，由

的氨基酸相连形成的肽称多肽(polypeptide)。肽链中的氨基酸分子因为脱水缩合而基团不全，被称