LEHNINGER PRINCIPLES OF BIOCHEMISTRYpds16.egloos.com/pds/200911/16/58/091013-pob_5e_ch16...David L Nelson and Michael M Cox LEHNINGER David L. Nelson and Michael M. Cox PRINCIPLES

David L Nelson and Michael M Cox

LEHNINGERDavid L. Nelson and Michael M. Cox

LEHNINGERPRINCIPLES OF BIOCHEMISTRY

Fifth Edition

CHAPTER 16CHAPTER 16The Citric Acid Cycley

© 2008 W. H. Freeman and Company

Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O

→ CoA + 2CO + 3NADH + FADH + GTP + 2H+ + H O→ CoA + 2CO2 + 3NADH + FADH2 + GTP + 2H+ + H2O

Pyruvate dehydrogenase complex= α-ketoglutarate deH2ase complex, α-ketoacid deH2ase complex (branched-chain amino acid 분해) g p , p ( )

4 vitamins

Pantothenate = CoA

Niacin = NAD+/NADH

(Ribo) flavin = FAD/FADH2

Thiamin = TPP

Acetyl/acyl-CoA : activated acetyl/acyl group carrier

R

Acyl

Lipoic acid : electron (hydrogen) carrier or acetyl/acyl group carrier

직경 50 nm, ribosome의약 5배 (bovine kidney)

PDH = E1 + E2 + E3

E1: pyruvate dehydrogenase TPPE2: Dihydrolipoyl transacetylase Lipoicacid HS-CoA 작용E3: Dihydrolipoyl dehydrogeanse FAD NAD+작용

참고로대장균의경우, E1 (24) + E2 (24) + E3 (12)로구성

아래세효소기능적으로매우유사 (E1 + E2 + E3 :주어진 species에서 E3는하나를공유)아래세효소기능적으로매우유사 (E1 E2 E3 : 주어진 species에서 E3는하나를공유)

Pyruvate dehydrogenase complex

= α-ketoglutarate deH2ase complex, α ketoglutarate deH2ase complex,

= α-ketoacid deH2ase complex (branched-chain amino acid 분해)

이들효소의특징

1. multi-enzyme complex : substrate channeling

즉, 중간과정ㅇ산물이유리되지않고최종산물만유리되어나옴.

2. 이효소 covalent modification과 allosteric regulation을통해조절됨.

1) Product inhibition: 반응산물인 acetyl CoA에의해 E2, NADH에의해 E3 가저해받음.

2) Feedback inhibition by nucleotide: GTP에의해 E1 저해받음. AMP에의해 E1 활성화

3) Covalent modification: E1의 Ser 기중의하나가 ATP에의해 phosphorylation이되면E1 저해받음. 이어 phosphatase에의해 P 제거되면다시활성띰.

TCA 회로의탄소 fateTCA 회 의탄소 fate

두개의탄소원자로된 acetyl unit가 cycle 속으로들어가고두개의탄소원자가 CO2 형태로 cycle을떠난다.

Cycle을떠나는두 C atom은그 round에 cycle로들어간 acetyl unit의 C atom이아님.

그다음 round에탄소원자 2개중적어도하나떠난다. (succinate/fumarate가 symmetric molecules)

또다음 round에나머지하나떠날수있다.

즉, 가장빠르면들어간 cycle을포함해 3번돌고다떠날수있다. 결국, (확률상) 떠나게된다.

Open form Closed form

Ordered bi bi rxn

Active site asp의 O가 acetyl CoA 의 methyl hydrogen 공격

Enol intermediate는 active site의 his에의해안정화

Enol재배열되면서 oaa의 carbonyl carbon공격Enol 재배열되면서 oaa의 carbonyl carbon 공격

Citroyl CoA 형성

이어가수분해되면서 CoA와 citrate 생성

Aconitase: iron-sulfur protein임.

[4Fe-4S] center 함유 =기질잡아줄뿐아니라, 반응매개

3Fe는 3cys에의해잡혀있음

4th Fe는 citrate의 carboxyl group4th Fe는 citrate의 carboxyl group, OH group과상호작용

4Fe-4S centerBasic residue