생명과학10. ATP

1분자의 아세틸 CoA가 시트르산회로와 전자전달계를 거칠 때, ATP 생성률을 계산하라.

 

 

10.1. 아세틸-CoA

아세틸-CoA(영어: acetyl-CoA) 또는 아세틸 조효소 A(영어: acetyl coenzyme A)는 단백질, 탄수화물 및 지질 대사 등 많은 생화학 반응에 참여하는 분자이다. 아세틸-CoA의 주요 기능은 아세틸기를 시트르산 회로에 전달하여 에너지 생산을 위해 산화되도록 하는 것이다. 조효소 A(CoA-SH 또는 CoA)에서 판토텐산의 하이드록시기는 3′-포스포아데노신 이인산과 인산에스터(인산에스테르) 결합을 하고 있으며, 판토텐산의 카복실기는 β-메르캅토에틸아민과 아마이드 결합을 하고 있다. 아세틸-CoA의 아세틸기(오른쪽 구조식에서 파란색으로 표시)는 β-메르캅토에틸아민 부분의 -SH기와 싸이오에스터(싸이오에스테르) 결합을 형성한다. 이러한 싸이오에스터 결합은 특히 반응성이 강한 "고에너지" 결합이다. 싸이오에스터 결합의 가수분해는 발열 반응(−31.5 kJ/mol)이다.

 

CoA는 해당과정을 통한 탄수화물의 분해와 β 산화를 통한 지방산의 분해에 의해 아세틸-CoA로 아세틸화된다. 아세틸-CoA는 시트르산 회로로 들어가서, 아세틸기가 이산화 탄소(CO2)와 물(H2O)로 산화되고, 방출되는 에너지를 이용해서 아세틸기 1분자당 11분자의 ATP와 1분자의 GTP를 생성한다.

 

콘라드 블로흐와 페오드르 리넨은 아세틸-CoA와 지방산 대사의 관련성을 발견한 공로로 1964년에 노벨 생리학·의학상을 수상했고 프리츠 리프만은 보조 인자인 조효소 A를 발견한 공로로 1953년에 노벨 생리학·의학상을 수상했다.

 

 

10.2. 미토콘드리아 밖에서

포도당의 농도가 높을 때 해당과정이 빠르게 일어나서 시트르산 회로에서 생성되는 시트르산의 양이 증가한다. 세포질에서 시트르산은 ATP 시트르산 분해효소(ATP citrate lyase)에 의해 아세틸-CoA와 옥살아세트산으로 분해되고, 이 과정에서 ATP는 ADP와 Pi로 가수분해된다.

 

포도당의 농도가 낮을 때 CoA는 아세틸-CoA 합성효소에 의해 아세트산을 사용하여 아세틸화되고, ATP 가수분해와 짝지워진다. 또한 에탄올은 알코올 탈수소효소에 의해 CoA의 아세틸화를 위한 탄소 공급원 역할을 한다. 발린, 류신, 아이소류신과 같은 가지사슬 케톤 생성 아미노산의 분해가 일어난다. 이들 아미노산들은 가지사슬 아미노기 전이효소(branched-chain aminotransferase)에 의해 α-케토산으로 전환되고, 결국 가지사슬 α-케토산 탈수소효소 복합체(branched-chain α-ketoacid dehydrogenase complex)에 의해 산화적 탈카복실화를 통해 아이소발레릴-CoA로 전환된다. 아이소발레릴-CoA는 아세틸-CoA 및 아세토아세트산으로 분해되기 전에 다른 CoA 유도체를 형성하기 위해 탈수소화, 카복실화 및 수화를 거친다.

 

 

10.3. 미토콘드리아 내에서

피부르산 탈수소효소 복합체 반응

포도당의 농도가 높을 때, 해당과정을 통해 아세틸-CoA가 생성된다. 피루브산은 산화적 탈카복실화를 거치면서 카복실기(이산화 탄소)를 소실하고 아세틸-CoA를 형성하는데, 이 과정에서 33.5 kJ/mol의 에너지를 방출한다. 피루브산이 아세틸-CoA로 산화적 탈카복실화되는 반응은 피루브산 탈수소효소 복합체에 의해 촉매된다. NADH의 산화로 방출된 고에너지 전자는 미토콘드리아 내막에 있는 일련의 전자 운반체의 산화, 환원에 의해 차례로 전달되며 최종 전자수용체인 산소(O2)가 전자를 받아 물(H2O)로 환원된다. 피루브산과 아세틸-CoA 사이의 다른 전환이 가능하다. 예를 들어, 피루브산 포름산 분해효소(pyruvate formate lyase)는 피루브산을 아세틸-CoA와 포름산으로 불균등화시킨다.

 

포도당의 농도가 낮을 때, 아세틸-CoA의 생성은 지방산의 β 산화와 관련이 있다. 먼저 지방산은 아실-CoA로 전환된다. 아실-CoA는 4가지 효소, 즉 아실-CoA 탈수소효소, 에노일-CoA 수화효소, β-하이드록시아실-CoA 탈수소효소, 아실-CoA 아세틸기 전이효소(싸이올레이스)에 의해 촉매되는 4단계의 탈수소화, 수화, 산화, 싸이올 분해 과정에서 분해된다. 이 과정에서 아세틸-CoA와 탄소 원자가 2개가 적은 새로운 아실-CoA가 생성된다.

지방산의 베타 산화

반응형

---

10.4. Cellular respiration and ATP

Energy flows into an ecosystem as sunlight and leaves as heat

Photosynthesis generates O2 and organic molecules, which are used in cellular respiration

Cells use chemical energy stored in organic molecules to generate ATP, which powers work

 

Catabolic pathways yield energy by oxidizing organic fuels

• Catabolic pathways release stored energy by breaking down complex molecules
• Electron transfer plays a major role in these pathways
• These processes are central to cellular respiration

Catabolic Pathways and Production of ATP

• The breakdown of organic molecules is exergonic
• Fermentation is a partial degradation of sugars that occurs without O2
• Aerobic respiration consumes organic molecules and O2 and yields ATP
• Anaerobic respiration is similar to aerobic respiration but consumes compounds other than O2
• Cellular respiration includes both aerobic and anaerobic respiration but is often used to refer to aerobic respiration
• Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose

   C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + Energy (ATP + heat)

 

Redox Reactions: Oxidation and Reduction

• The transfer of electrons during chemical reactions releases energy stored in organic molecules
• This released energy is ultimately used to synthesize ATP

The Principle of Redox

• Chemical reactions that transfer electrons between reactants are called oxidation-reduction reactions, or redox reactions
• In oxidation, a substance loses electrons, or is oxidized
• In reduction, a substance gains electrons, or is reduced (the amount of positive charge is reduced)
• The electron donor is called the reducing agent
• The electron receptor is called the oxidizing agent
• Some redox reactions do not transfer electrons but change the electron sharing in covalent bonds
• An example is the reaction between methane and O2

Oxidation of Organic Fuel Molecules During Cellular Respiration

During cellular respiration, the fuel (such as glucose) is oxidized, and O2 is reduced

 

Stepwise Energy Harvest via NAD+ and the Electron Transport Chain

• In cellular respiration, glucose and other organic molecules are broken down in a series of steps
• Electrons from organic compounds are usually first transferred to NAD+, a coenzyme
• As an electron acceptor, NAD+ functions as an oxidizing agent during cellular respiration
• Each NADH (the reduced form of NAD+) represents stored energy that is tapped to synthesize ATP

• NADH passes the electrons to the electron transport chain
• Unlike an uncontrolled reaction, the electron transport chain passes electrons in a series of steps instead of one explosive reaction
• O2 pulls electrons down the chain in an energy-yielding tumble
• The energy yielded is used to regenerate ATP

The Stages of Cellular Respiration: A Preview

Harvesting of energy from glucose has three stages

• Glycolysis (breaks down glucose into two molecules of pyruvate)
• The citric acid cycle (completes the breakdown of glucose)
• Oxidative phosphorylation (accounts for most of the ATP synthesis)

 

• The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions
• Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration
• A smaller amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level phosphorylation
• For each molecule of glucose degraded to CO2 and water by respiration, the cell makes up to 32 molecules of ATP

Glycolysis harvests chemical energy by oxidizing glucose to pyruvate

• Glycolysis (“sugar splitting”) breaks down glucose into two molecules of pyruvate
• Glycolysis occurs in the cytoplasm and has two major phases(Energy investment phase, Energy payoff phase)
• Glycolysis occurs whether or not O2 is present

 

 

After pyruvate is oxidized, the citric acid cycle completes the energy-yielding oxidation of organic molecules

In the presence of O2, pyruvate enters the mitochondrion (in eukaryotic cells) where the oxidation of glucose is completed

 

Oxidation of Pyruvate to Acetyl CoA

• Before the citric acid cycle can begin, pyruvate must be converted to acetyl Coenzyme A (acetyl CoA), which links glycolysis to the citric acid cycle
• This step is carried out by a multienzyme complex that catalyses three reactions

The Citric Acid Cycle

• The citric acid cycle, also called the Krebs cycle, completes the break down of pyruvate to CO2
• The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn

• The citric acid cycle has eight steps, each catalyzed by a specific enzyme
• The acetyl group of acetyl CoA joins the cycle by combining with oxaloacetate, forming citrate
• The next seven steps decompose the citrate back to oxaloacetate, making the process a cycle
• The NADH and FADH2 produced by the cycle relay electrons extracted from food to the electron transport chain

During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis

• Following glycolysis and the citric acid cycle, NADH and FADH2 account for most of the energy extracted from food
• These two electron carriers donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation

The Pathway of Electron Transport

• The electron transport chain is in the inner membrane (cristae) of the mitochondrion
• Most of the chain’s components are proteins, which exist in multiprotein complexes
• The carriers alternate reduced and oxidized states as they accept and donate electrons
• Electrons drop in free energy as they go down the chain and are finally passed to O2, forming H2O

• Electrons are transferred from NADH or FADH2 to the electron transport chain
• Electrons are passed through a number of proteins including cytochromes (each with an iron atom) to O2
• The electron transport chain generates no ATP directly
• It breaks the large free-energy drop from food to O2 into smaller steps that release energy in manageable amounts

The Energy-Coupling Mechanism

• Electron transfer in the electron transport chain causes proteins to pump H+ from the mitochondrial matrix to the intermembrane space
• H+ then moves back across the membrane, passing through the protein complex, ATP synthase
• ATP synthase uses the exergonic flow of H+ to drive phosphorylation of ATP
• This is an example of chemiosmosis, the use of energy in a H+ gradient to drive cellular work

• The energy stored in a H+ gradient across a membrane couples the redox reactions of the electron transport chain to ATP synthesis
• The H+ gradient is referred to as a proton-motive force, emphasizing its capacity to do work

An Accounting of ATP Production by Cellular Respiration

• During cellular respiration, most energy flows in this sequence:

  glucose → NADH → electron transport chain → proton-motive force → ATP

• About 34% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 32 ATP
• There are several reasons why the number of ATP is not known exactly

Fermentation and anaerobic respiration enable cells to produce ATP without the use of oxygen

• Most cellular respiration requires O2 to produce ATP
• Without O2, the electron transport chain will cease to operate
• In that case, glycolysis couples with anaerobic respiration or fermentation to produce ATP
• Anaerobic respiration uses an electron transport chain with a final electron acceptor other than O2, for example sulfate
• Fermentation uses substrate-level phosphorylation instead of an electron transport chain to generate ATP

Types of Fermentation

• Fermentation consists of glycolysis plus reactions that regenerate NAD+, which can be reused by glycolysis
• Two common types are alcohol fermentation and lactic acid fermentation
• In alcohol fermentation, pyruvate is converted to ethanol in two steps(The first step releases CO2, The second step produces ethanol)
• Alcohol fermentation by yeast is used in brewing, winemaking, and baking

• In lactic acid fermentation, pyruvate is reduced by NADH, forming lactate as an end product, with no release of CO2
• Lactic acid fermentation by some fungi and bacteria is used to make cheese and yogurt
• Human muscle cells use lactic acid fermentation to generate ATP when O2 is scarce

Comparing Fermentation with Anaerobic and Aerobic Respiration

• All use glycolysis (net ATP = 2) to oxidize glucose and harvest chemical energy of food
• In all three, NAD+ is the oxidizing agent that accepts electrons during glycolysis
• The processes have different mechanisms for oxidizing NADH: (In fermentation, an organic molecule (such as pyruvate or acetaldehyde) acts as a final electron acceptor, In cellular respiration electrons are transferred to the electron transport chain)
• Cellular respiration produces 32 ATP per glucose molecule; fermentation produces 2 ATP per glucose molecule
• Obligate anaerobes carry out fermentation or anaerobic respiration and cannot survive in the presence of O2
• Yeast and many bacteria are facultative anaerobes, meaning that they can survive using either fermentation or cellular respiration
• In a facultative anaerobe, pyruvate is a fork in the metabolic road that leads to two alternative catabolic routes

The Evolutionary Significance of Glycolysis

• Ancient prokaryotes are thought to have used glycolysis long before there was oxygen in the atmosphere
• Very little O2 was available in the atmosphere until about 2.7 billion years ago, so early prokaryotes likely used only glycolysis to generate ATP
• Glycolysis is a very ancient process

Glycolysis and the citric acid cycle connect to many other metabolic pathways

• Gycolysis and the citric acid cycle are major intersections to various catabolic and anabolic pathways

The Versatility of Catabolism

• Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration
• Glycolysis accepts a wide range of carbohydrates
• Proteins must be digested to amino acids; amino groups can feed glycolysis or the citric acid cycle
• Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA)
• Fatty acids are broken down by beta oxidation and yield acetyl CoA
• An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate

Biosynthesis (Anabolic Pathways)

• The body uses small molecules to build other substances
• These small molecules may come directly from food, from glycolysis, or from the citric acid cycle

Regulation of Cellular Respiration via Feedback Mechanisms

• Feedback inhibition is the most common mechanism for metabolic control
• If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down
• Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway

 

---

Reference

http://chemistry.elmhurst.edu/vchembook/623acetylCoAfate.html

Acetyl CoA Crossroads

https://web.archive.org/web/20170531033511/http://library.med.utah.edu/NetBiochem/FattyAcids/2_4.html

Fatty Acids -- Structure of Acetyl CoA

Hynes, Michael J.; Murray, Sandra L. (2010년 7월 1일). “ATP-Citrate Lyase Is Required for Production of Cytosolic Acetyl Coenzyme A and Development in Aspergillus nidulans”

Wellen, Kathryn E.; Thompson, Craig B. (2012년 4월 1일). “A two-way street: reciprocal regulation of metabolism and signalling”

Chatterjea (2004년 1월 1일). 《Textbook of Biochemistry for Dental/Nursing/Pharmacy Students》

Ragsdale, S. W. (2004). “Life with carbon monoxide”. 《CRC Critical Reviews in Biochemistry and Molecular Biology》 39: 165–195.

Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2002). 《Biochemistry》

Pearson Education : Campbell biology