CHAPTER 17 The Metabolism – An Overview

17-1 Is metabolism similar in different organisms?

 Living Things Exhibit Metabolic Diversity
1. Organism show remarkable similarity in their major metabolic pathways
2. And yet, living things also exhibit metabolic diversity
3. The flow of energy in the biosphere and the carbon and oxygen cycles are intimately releated
4. The impetus(推動力) driving the cycle is light energy
 Oxygen Is Essential to Life for Aerobes

1. Autotrophs use CO2；heterotrophs use organic carbon

2. Phototrophs use light；chemotrophs use organic and inorganic electron donors
3. Phototrophs use light to drive synthesis of organic molecules
4. Heterotrophs use these as building blocks CO2, O2 and H2O are recycled

17-2 What can be learned from metabolic maps?

 The Metabolic Map Can Be Viewed as a Set of Dots and Lines
 Alternative Models Can Provide New Insights into Pathways
1. Pathways consist of sequential steps
2. The enzymes may be separate or multienzyme complex or be a membrane-bound system
3. New research indicates that multienzyme complex are more common than once thought

4. The traditional view of a metabolic pathway is metabolite-centric

 5. Julia Gerrard has proposed that a protein-centric view is more information for some purpose
6. A simplified version of the protein-centric view where proteins in the pathway form multifunctional
complex
7. Types of multienzyme systems
 physically separate, soluble enzymes with diffusing intermediates
 multienzyme complex
 membrane-bound multienzyme system

17-3 How do anabolic and catabolic processes form the core of metabolic pathways?
 Anabolism and Catabolism Are Not Mutually Exclusive
1. Catabolic pathways are characteristically energy yielding, whereas anabolic pathways are energy
requiring
2. Catabolic reactions are usually exergonic, and often the chemical energy released is captured in the
form of ATP
3. NAD+ reduction is a part of catabolism；NADPH oxidation is an important aspect of anabolism
4. Anabolism consumes chemical energy in the form of ATP and uses NADPH as a source of high energy
electrons for reductive reactions of anabolism
5. anabolism and catabolism occur simultaneously in the cell
 Amphibolic Intermediates Play Dual Roles
1. Catabolic pathways converge to a few end products
2. Anabolic pathway diverge to synthesize many biomolecules
3. Some pathways serve both in catabolism and anabolism, called amphibolic
 Corresponding Pathways of Catabolism and Anabolism Differ in Important Ways
1. Some steps may be common to both
2. This also allows regulation mechanisms to turn one pathway on and the other off
3. Three stages of catabolism：
 proteins, polysaccharides and lipids are broken down into their component building blocks
 building blocks are degraded into common product, the acetyl-CoA
 catabolism converges to three principal and products：water, carbon dioxide, ammonia
重要的 Common pathway：pyruvate→acetyl-CoA→citric acid cycle→oxidative phosphorylation
4. Metabolic regulation requires different pathways for oppositely directed metabolic sequences
(regulated independently)
5. Parallel sequences proceed by independent routes
6. Only one reaction has two different enzymes
 ATP Serves in a Cellular Energy Cycle
1. ATP is formed via photosynthesis in phototrophic cells or catabolism in heterotrophic cells
2. ATP is the energy currency of cells
3. Energy-requiring cellular activities are powered by ATP hydrolysis. Liberating ADP and Pi
4. Comparison of the state of reduction of carbon atoms in biomolecules：
 CO2 is the final product of catabolism and the most oxidized form of carbon in the biosphere

 An overview of cellular respiration

1. NADH and FADH2：donate electrons to the electron transport chain (ETC), which powers ATP
synthesis via oxidative phosphorylation
2. NAD+ Collects Electrons Released in Catabolism
 NAD+-NADH shuttle is used in oxidative phosphorylation
 hydrogen and electrons released in the source of oxidative catabolism are transferred as hydride
 ions to the pyridine nucleotide, NAD+, to form NADH and H+ in dehydrogenase reactions
在氧化磷酸化的過程中，靠 chemiosmosis 與 electron transport chain 生成 ATP
→NADH 生成 3ATP；FADH2 生成 2ATP
3. NADPH Provides the Reducing Power for Anabolic Processes
 NADPH providing the reducing equilvalents is the high -energy hydrogens for reductive biosyn
 transfer of reducing equivalents from catabolism to anabolism via the NADPH cycle
 in photosynthetic organisms the energy of light is used to pull electrons from water transfer them
to NADP+

 Coenzymes and Vitamins Provide Unique Chemistry and Essential Nutrients to Pathways

17-4 What experiments can be used to elucidate metabolic pathways?

 Mutations Create Specific Metabolic Blocks
1. Mutation in a gene encoding an enzyme often results in an inability to synthesize the enzyme in an
active form
2. leads to a block in the metabolic pathway at the point where the enzyme acts, and the enzyme’s
substrate accumulates
 Isotopic Tracers Can Be Used as Metabolic Probes
1. Another approach to the elucidation of metabolic sequences is to feed cells a substrate or metabolic
intermediate labeled with a particular isotopic form of an element that can be traced
2. isotopes provide reliable tags for observing metabolic changes

 NMR Spectroscopy Is a Noninvasive Metabolic Probe

1. The nuclear magnetic resonance (NMR) absorption is influence in predictable ways by the chemical
nature of its neighboring atoms and by its dynamic behavior
 Metabolic Pathways Are Compartmentalized Within Cells
1. 可以利用不同轉速的離心方法，將細胞內的胞器提取出來
2. The flow of metabolic intermediates in the cell is spatially and chemically segregated
(compartmentalization) →糖解作用發生在細胞質；TCA cycle 在粒腺體內
17-5 What can the metabolome tell us about a biological system?
 Metabolome is the complete set of low molecular weight molecule present in an organism or extracted
by it under a given set of circumstances
 Metabolomics is the systematic identification and quantitation of all these metabolites in a given
organism or sample
 Mass spectrometry (MS) and NMR are both powerful techniques for metabolomic analysis
17-6 What food substances form the basis of human nutrition?
 Protein is a rich source of nitrogen and also provides essential amino acids
1. glucogenic→glucose；ketogenic→fatty acid/keto acid
 Carbohydrates provides needed energy and essential components for nucleotides and nucleic acids
 Lipids provide essential fatty acids that are key components of membranes and also important signal
molecules
 Fiber whether soluble or insoluble can be a beneficial component in the human diet
1. Dietary fiber cannot digest by human
2. Cellulose/hemicellulose
 Vitamins and minerals
 A summary of vitamin and coenzymes
1. Many vitamins are enzymes that bring unusual chemistry to enzyme active site
Vitamin Coenzyme form Function
Water-soluble
Thiamine(Vitamin Thiamine pyrophosphate (TPP) Decarboxylation of 𝛼-keto and formation and
B1) cleavage of 𝛼-hydroxyketones
Niacin (B3) NAD+ and NADP+ Hydride transfer
Riboflavin (B2) FADH、FADH2、FMN One and two electron transfer
Pantothenic acid (B6) Coenzyme A Activation of acyl groups
Cobalamin (B12) 5’-deoxyadenosylcobalamin Ribonucleotides to deoxyribonucleotides
biotin Biotin-lysine complexes Carrier of carboxyl groups in carboxylation reactions
Lipoic acid Lipoyl-lysine complex Decarboxylation of 𝛼-keto acids
Folic acid THF Acceptor and donor od C unit for all oxidation
Fat-coluble
Retinol (Vitamin A)
Retinal (Vitamin A)
Retinoic acid (Vitamin A)
Ergocalciferol (Vitamin D2)
Cholecalciferol (Vitamin D3)
𝛼-Tocopherol (Vitamin E)
Menaquinone (VitaminK)
 Thiamine (Vitamin B1)
1. 構造：

 a thiazole ring joined to a substituted pyrimidine by a methylene bridge

活性分子：thiamin diphosphate (TPP)
活化反應需消耗 ATP，並在 TPP-synthetase 作用
2. 功能：在代謝體內 carbohydrate 有重要影響，多為酵素催化的輔酶
 the decarboxylation of 𝛼-keto acids：de-carbohydrate metabolism 反應
 the formation and cleavage of 𝛼-hydroxyketones

 all these reactions depend on accumulation of negative charge on the carbonyl carbon
 TPP facilitates these reactions by stabilizing this negative charge
 Niacin (nicotinic acid, Vitamin B3)
1. Some vitamins contain Adenine nucleotides→ all use the adenine nucleotide group solely for
binding to the enzyme
 pyridine dinucleotides (NAD, NADP)
 flavin mono- and dinucleotides (FMN(沒有), FAD)
 coenzyme A (CoA)

2. Niacin(菸鹼素)分類：Nicotinic acid、nicotinamide、兩者皆會被轉成 NAD 和 NADP(氧化態)

再還原反應或呼吸作用時，作為電子接受者或氫的提供者
 NAD+ and NADP+ participate exclusively in two-electron transfer reactions
 Riboflavin (Vitamin B2)
1. Vitamin B2 介紹：核黃素(riboflavin)為 FAD、FMN 的前驅物
 FAD 與 FMN 為能量產生與呼吸作用的還原反應中的重要酵素
 flavins are stronger oxidizing agents than NAD+ and NADP+
 FMN is not a true nucleotide; FAD is not a dinucleotide
2. 生化功能：Flavin 作為 coenzyme 在許多氧化還原反應中扮演電子攜帶者
→要注意中間產物的顏色與電子轉移

 Pantothenic acid (Vitamin B5)

1. 活化態：與 coenzyme A 結合(CoASH)、ACP
2. 功能：參與合成 CoA 與 TCA cycle
  activation of acyl group for transfer by nucleophilic attack
 activation of alpha hydrogen of the acyl group for absorbance as a proton
 Pyridoxal, pyridoxine, pyridoxamine (Vitamin B6)
1. 由三種主要化合物構成：pyridoxine、pyridoxal、pyridoxamine
2. 活化態：pyridoxal phosphate (PLP)
3. Catalyzes reactions involving amino acids → formation of stable Schiff base adducts a conjugated
electron sink system that stabilizes traction intermediates

 Cobalamin (Vitamin B12)

1. 唯一的食物來源是動物體，所以吃素的人經常缺 B12，且 Vitamin B12 僅會由微生物合成
2. 中心：Vitamin B12 擁有 Co3+中心
3. B12 catalyzes 3 kinds of reaction：

 Vitamin C
1. 分子相當不穩定，照光易分解
2. 鳥類和哺乳類體內缺乏酵素，故無法自行合成 Vitamin C
3. Vitamin C is reasonably strong reducing agent
4. It functions as an electron carrier
5. 功用：膠原蛋白的合成→形成 biotin-lysine complex
→Biotin is covalently linked to a protein via the amino group of a lysine residue
 Biotin(Vitamin B7)
1. 與各種 CoA 的酵素常一起出現，因為生物素主要功能就是把 CO2 轉到其他分子上
2. The carboxylation that requires ATP, CO2 or HCO3-
 Lipoic acid
1. Lipoic acid is a ring on a chain and is linked to a lysine on its protein
2. Lipoic acid functions to couple acyl-group transfer and electron transfer during oxidation and de-
carboxylation of 𝛼-keto acids
 Folic acid
1. 活化態：tetrahydrofolate (THF)
2. Folates are donor of 1-C units for all oxidation levels of carbon except that of CO2
3. Folic acid and B12 can add a single carbon species to other molecules
 Vitamin A
1. 脂溶性維他命
2. 具有三種主要活化態： Retinol、Retinoic acid、Retinal
3. The steps transfer retinal into rhodopsin：
 trans-retinol (Vit A)在 retinol dehydrogenase 的氧化作用下形成 trans-retinal
 trans-retinal 再由 retinal isomerase 轉成 cis-retinal
 最後透過 Opsin 的參與，形成 rhodopsin(中間有 Schiff base 連接 C=N-)

 Vitamin D (~calciferol)
1. 存在於皮膚中，是少數能由人體自行合成的脂溶性維生素
2. Regulate calcium and phosphorus homeostasis
3. 7-Dhydrocholesterol 經過 UV 照光變成 pre-Vitamin D，會在自發轉成 Vitamin D3 (cholecalciferol)
4. Cholecalciferol 會透過肝臟轉成 25-Hydroxyvitamin D5 (major circulating form)
5. 再由腎臟形成 1,25-Dihydroxyvitamin D3 (active form)

 Vitamin E (~pherol)
1. 可以抗氧化，避免膜氧化
 Vitamin K (~quinone)
1. K2 essential for blood clotting