Chapter 5. 주요 대사 경로

The TCA CycleThe TCA Cycle• aerobic pathways

glycolysis TCA cycle electron transport ATP generation

The TCA Cycle: A Brief SummaryThe TCA Cycle: A Brief Summary• entry of new carbon units into the TCA cycle : acetyl-CoA (2C)

Physiological importance of TCA cycle

TCA cycle 은 에너지 영양소를 산화시켜 ATP 를 생성하는 이화작용 (catabolism) 측면에서 뿐만 아니라 생체에 필요한 화합물을 합성하는 동화작용 (anabolism) 중요하다 .

따라서 TCA cycle 은 이화작용과 동화작용에 모두 관계되는 대사이므로 amphibolic pathway 라고 한다 .

에너지영양소 즉 탄수화물 , 단백질 및 지질의 공통적이고 최종적인 산화경로이다 .

생합성에 필요한 다양한 전구물질 (precursor) 을 생성한다 .

• oxidative decarboxylation

Pyr + CoA + NAD+ → acetyl-CoA + CO2 + NADH + H+

• catalyzed by pyruvate decarboxylase complex (PDC)

: a multi enzyme complex

The Bridging Step: Oxidative Decarboxylation of PyruvateThe Bridging Step: Oxidative Decarboxylation of Pyruvate

• glycolysis occurs in the cytoplasm (eukaryotic cells)

TCA cycle reaction and all subsequent steps of aerobic

metabolism occurs in the mitochondria (eukaryotic cells)

• pyruvate must first enter the mitochondria to enter the TCA cycle

Transport of pyruvate across mitochondrial membrane

The mechanism of pyruvate dehydrogenase reaction.: mitochondrial matrix

1. Entry into Cycle: The Citrate Synthase Reaction1. Entry into Cycle: The Citrate Synthase Reaction

Keq near 1 highly exergonic

• [OAA] in mitochondria : much less than 1 mM

: however, the strong, negative ΔGo’ drives the reaction forward

2. The Isomerization of Citrate by Aconitase2. The Isomerization of Citrate by Aconitase

3. Isocitrate Dehydrogenase: The First Oxidation in Cycle3. Isocitrate Dehydrogenase: The First Oxidation in Cycle

NAD+ NADH+ H+

IDH

• oxidative decarboxylation of isocitrate

to yield -KG(ketoglutarate)

• Go’: -8.4 kJ/mol, sufficiently exergonic

• two-step reaction

i) oxidation of isocitrate to oxalosuccinate

ii) -decarboxylation

-KG Dehydrogenase: A Second Decarboxylation-KG Dehydrogenase: A Second Decarboxylation

• a second oxidative decarboxylation (a multienzyme complex)

• produces NADH and thioester products

5. Succinyl-CoA Synthetase: 5. Succinyl-CoA Synthetase: A Substrate-Level phosphorylationA Substrate-Level phosphorylation

• generation of GTP or ATP: substrate-level phosphorylation

• succinyl-CoA synthetase or succinate thiokinse (ligase)

• NDP kinase catalyzes the exchange the terminal P group of

ADP and GTP

GTP + ADP ATP + GDP

6. Succinate Dehydrogenase: An Oxidation Involving FAD6. Succinate Dehydrogenase: An Oxidation Involving FAD

• a membrane-bound enzyme (part of electron transport chain)

: part of succinate-coenzyme Q reductase

• integral membrane protein tightly associated with inner

mitochondrial membrane

7. Fumarase Catalyzes 7. Fumarase Catalyzes TransTrans-Hydration of Fumarate-Hydration of Fumarate

• stereospecific hydration of fumarate to give L-malate

(trans addition of water molecule)

8. Malate Dehydrogenase: Completing the Cycle8. Malate Dehydrogenase: Completing the Cycle

• very endergonic reaction (Go’= +30 kJ/mol)

• [OAA] in mitochondria is usually quite low

• reaction pulled forward

by the favorable citrate synthase reaction

A Summary of the CycleA Summary of the Cycle

A Summary of the CycleA Summary of the Cycle

RESPIRATIONRESPIRATION

전자 전달 체인 (Electron Transport Chain)

: 해당과정에 필요한 NAD 와 생합성에 필요한 ATP 재생 또는 생성

산화적 인산화 반응 (Oxidative Phosphorylation):

NADH + H+ or FADH2

Electron carriers

ATP generation

Proton gradient

ATPase

3ATP /NADH 2ATP /FADH2

Yield:

Oxidative phosphorylationOxidative phosphorylation

Oxidative phosphorylationOxidative phosphorylation

• NADH dehydrogenase

• Succinate dehydrogenase

• Cytochrome bc1

• Cytochrom oxidase

• Quinon (Q)

• Cytochrom c

The electron acceptor is molecular oxygen.

These complexes are proton pumps Electron carriers

SummarySummary

NADH, FADH2 and ATP formation during Aerobic Catabolism of GlucoseNADH, FADH2 and ATP formation during Aerobic Catabolism of Glucose

NADH FADH2 ATP Total ATP

Glycolysis 2 - 2 6

Oxidative decarboxylation of pyruvate

2 - - 6

TCA cycle 6 2 2 24

Total 10 2 4 36

P/O ratio: 전자 수용체로 사용되는 산소원자 하나당 생성된 인산 결합 (ADP + Pi →ATP)

Glucose + 36 Pi + 36 ADP + 6O2 → 6CO2 +6H2O + 36 ATP

Glucose MetabolismOrganic Compounds

(Glucose)

ATP

EMP

Pyruvate

Acetyl-coA

TCACycle

Acetyl-coA

Formate

AcetateEthanol NADH

ETC

ATP

EDPPP

NADPH

Ribose

AerobicAnaerobic

Lactate

HMP pathway(Hexose-monophosphate)

HMP pathway is used

for biosynthesis

•동화작용을 지탱하기 위한

환원력 (NADPH) 마련 - 생합성에 이용

• 생합성에 필요한 탄소계 골격물질 (C3, C4, C5, C7 등 ..) 생성 :

리보오스 (Ribose), 퓨린계 (purines) 화합물 , 보조효소 , 방향족 아미노산 합성에

중요

The TCA Cycle Provides Intermediates for Biosynthetic Pathways

Amino acids synthesisFig. 5.8

혐기성 대사혐기성 대사

Anaerobic Respiration: 산소가 없는 상태에서의 에너지 생산

Fermentation: the pyruvate molecule can follow other anaerobic pathways to regenerate the NAD+ necessary for glycolysis to continue.

혐기성 대사혐기성 대사

Entner-Doudoroff PathwayEntner-Doudoroff Pathway

An alternate series of reactions that catabolize glucose to pyruvate using a

set of enzymes different from those used in either glycoslysis

Distinct features of the Entner-Doudoroff pathway

• Occurs only in prokaryotes

• Uses 6-phosphogluconate dehydrase and 2-keto-3-deoxyglucosephophate al

dolase to create pyruvates from glucose.

• Does not produce gases during its metabolic process, distinguishing them fro

m microorganisms of enteric species.

•Net yield of 1 ATP as well as 1 NADH and 1NADPH for every glucose

Light reaction in photosynthesis Light reaction in photosynthesis

• This reaction produce ATP and NADH.

• Photosystem II & I (PSII & PSI) convert solar energy electrical energy

• H2O + NADP+ + Pi + ADP → oxygen + NADPH + H+ + ATP

Light reaction in photosynthesis Light reaction in photosynthesis

Calvin-Benson CycleCalvin-Benson Cycle (Calvin Cycle)(Calvin Cycle)

““Dark reaction”Dark reaction”

• This cycle occurs in the stroma

• Calvin cycle requires

18 ATP, 12 NADPH, and CO2.

• It is the opposite of the TCA cycle

(TCA: produces ATP and NADP and glucose is broken down to make CO2. )

• This cycle uses ATP, NADPH,  and CO2 is used to make glucose

• CO2 + NADPH + H+ + ATP → 1/6 glucose + NADP+ + ADP + Pi