生化英文要点

CHAPTER ONE
Both D-amino acids and non-α-amino acids occur in nature, but only L-α-amino acids are present in proteins.
自然界中同时存在D-氨基酸和非α-氨基酸，但人体蛋白质中只有L-α-氨基酸。

• All amino acids possess at least two weakly acidic functional groups, R-NH3+ and R-COOH. Many also possess additional weakly acidic functional groups such as -OH, -SH, guanidino, or imidazole
groups.
所有的氨基酸至少含有两个弱酸性功能基团（R-NH3+和R-COOH）。

有些氨基酸含有其它弱酸性功能基团，如羟基，巯基，胍基和咪唑。

• pI is the pH at which an amino acid bears no net charge and thus does not move in a direct current electrical field.
在某一PH的溶液中，氨基酸不带电并在直流电场中不移动，此时溶液的PH称为该氨基酸的等电点。

• Of the biochemical reactions of amino acids, The most important is the formation of peptide bonds.
在氨基酸的生化反应中最重要的就是肽键的机构。

• The R groups of amino acids determine their un ique biochemical functions. Amino acids are classified as basic, acidic, aromatic, aliphatic, or sulfur-containing based on the properties of their R groups.
氨基酸的R基团决定其独特的生物化学功能。

根据其R基团的性质，氨基酸可以分为碱性氨基酸，酸性氨基酸，芳香族氨基酸，脂肪族氨基酸和含硫的的氨基酸。

• Peptides are named for t he number of amino acid residues present, and as derivatives of the carboxyl terminal residue. The primary structure of a peptide is its amino acid sequence, starting from the aminoterminal residue.
肽是依据氨基酸残基的数目命名的，命名为羧基末端残基衍生物。

从氨基末端开始的氨基酸序列构成蛋白质的一级结构。

• T he partial double-bond character of the bond that links the carbonyl carbon and the nitrogen of a peptide renders four atoms of the peptide bond coplanar and restricts the number of possible peptide conformations.
连接羰基碳和酰胺氮的半双键特性使肽键的四个原子共平面并且限制肽的可能构型。

Long amino acid polymers or polypeptides constitute the basic structural unit of proteins, and the structure of a protein provides insight into how it fulfills its functions.
Proteins may be classified on the basis of the solubility, shape, or function or of the presence of a prosthetic group such as heme. Proteins perform complex physical and catalytic functions by positioning specific chemical groups in a precise three-dimensional arrangement that is both functionally efficient and physically strong.
长氨基酸聚合物或多肽组成蛋白质的基本结构单元，蛋白质的结构决定其功能机制。

蛋白质可根据其可溶性，形状，功能和辅助基团（如亚铁血红素）来分类。

蛋白质通过精密的三维结构中特殊的化学基团来执
行复杂的物理和催化功能。

• The gene-encoded primary structure of a polypeptide is the sequence of its amino acids. Its secondary structure results from folding of polypeptides into hydrogen-bonded motifs such as the α helix, the
β-pleated sheet, β bends, and loops. Combinations of these motifs can form supersecondary motifs.
由基因编码的蛋白质一级机构就是其氨基酸序列。

多肽折叠成由氢键连接的模体构成蛋白质的二级机构，如α-螺旋，β-折叠，β-转角和环。

这些模体相互结合可以形成超级二级模体。

• Tertiary structure concerns the relationships between secondary structural domains. Quaternary structure of proteins with two or more polypeptides (oligomeric proteins) is a feature based on the spatial relationships between various types of polypeptides.
蛋白质的三级结构与其二级结构单元之间的关系有关。

由两条及两条以上多肽构成的蛋白质的四级机构的特性使由不同类型多肽之间的空间关系决定的。

• Primary structures are stabilized by covalent peptide bonds. Higher orders of structure are stabilized by weak forces—multiple hydrogen bonds, salt (electrostatic) bonds, and association of hydrophobic R groups. 蛋白质的一级机构是由共价肽键来稳固的。

其高级机构是由弱键稳固的，如复杂的氢键，离子键（盐键）和由R基团之间的疏水键。

• The phi (Φ) angle of a polypeptide is the angle about the Cα⎯N bond; the psi (Ψ) angle is that about the
Cα-Co bond. Most combinations of phi-psi angles are disallowed due to steric hindrance. The phi-psi angles that form the α helix and the β sheet fall within the lower and upper left-hand quadrants of a Ramachandran plot, respectively.
Cα与N的键旋转角度以Φ表示，Cα与Co的键旋转角度以Ψ表示。

由于空间位阻，大部分Φ角和Ψ角之间不能相互结合，形成α-螺旋和β-折叠的Φ-Ψ角分别位于拉氏图的上下左手的四分圆之间。

• Protein folding is a poorly understood process. Broadly speaking, short segments of newly synthesized Synthesized polypeptide fold into secondary structural units. Forces that bury hydrophobic regions from solvent then drive the partially folded polypeptide into a ―molten globule‖ in which the modules of secondary structure are rearranged to give the native conformation of the protein.
蛋白质折叠过程至今不是很清楚。

一般说来，新合成的短多肽片段被折叠成二级机构。

将疏水区埋在溶剂里面的力使部分折叠的多肽进一步折叠成“熔球”，二级机构重排形成蛋白质的天然构象。

• Proteins that assist folding include protein disulfid e isomerase, proline-cis，trans,-isomerase, and the chaperones that participate in the folding of over half of mammalian proteins. Chaperones shield newly synthesized polypeptides from solvent and provide an environment for elements of secondary structure to emerge and coalesce into molten globules.
帮助折叠的蛋白质如二硫化物异构酶，脯氨酸，顺反异构酶是分子伴侣，它参与大半哺乳动物蛋白质的折叠。

分子伴侣保护新合成的多肽不被溶解，通过提供一个保护环境从而加速蛋白质折叠成天然构象或形成四级机构。

• Techniques for study of higher orders of protein structure include x-ray crystallography, NMR
spectroscopy, analytical ultracentrifugation, gel filtration, and gel electrophoresis.
研究蛋白质高级机构的技术包括X(射)线衍射晶体分析法，X(射)线衍射晶体分析法，分析超速离心，凝胶过滤法和凝胶电泳(法)。

• Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary structure of a naturally occurring protein, PrPc. When PrPc interacts with
its pathologic isoform PrPSc, its conformation is transformed from a predominantly α-helical structure to the β-sheet structure characteristic of PrPSc.
阮病毒是一种缺少核酸的蛋白质颗粒，它可以引起致命的可传播的海绵状脑病如克罗伊茨费尔特-雅各布病，绵羊瘙痒病和牛海绵样脑病。

阮病毒病是由一种叫做PrPc的天然蛋白质的二三级机构发生改变引起的。

当PrPc与其病态的结构PrPSc作用时，它的结构由富含α-螺旋转变为β-折叠变为PrPSc。

Myoglobin is monomeric; he moglobin is a tetramer of two subunit types (α2β2 in HbA). Despite having different primary structures, myoglobin and the subunits of hemoglobin have nearly identical secondary and tertiary structures.
肌红蛋白是单体结构；血红蛋白是四聚体，它由两个α2和两个β2亚基构成。

尽管它们有不同的一级结构，但肌红蛋白和血红蛋白的亚基有几乎完全相同的二级结构和三级结构。

• Heme, an essentially planar, slightly puckered, cyclic tetrapyrrole, has a central Fe2+ linked to all four nitrogen atoms of the heme, to histidine F8, and, in oxyMb and oxyHb, also to O2.
亚铁血红素本质上是轻微皱褶的平面环状四吡咯，中心的亚铁离子与血红素的四个氮原子配位结合，一个配位键和肌红蛋白的F8组氨酸残基结合，在氧合Mb和氧合Hb中与氧气结合。

• The O2-binding curve for myoglobin is hyperbolic, but for hemoglobin it is sigmoidal, a consequence of cooperative interactions in the tetramer. Cooperativity maximizes the ability of hemoglobin both to load
O2 at the PO2 of the lungs and to deliver O2 at the PO2 of the tissues.
Hb和Mb的氧解离曲线，前者为直角双曲线，后者为S状曲线，这是四聚体协同效应的结果。

协同效应使血红蛋白在肺的氧分压下装载氧气和在组织的氧分压下释放氧气的能力同时达到最大。

• Relative affinities of different hemoglobins for oxygen are expressed as P50, the PO2 that half-saturates them with O2. Hemoglobins saturate at the partial pressures of their respective respiratory organ, eg, the lung or placenta.
不同血红蛋白的相对氧亲和力可表示为P50，即氧饱和度达到一半时的氧分压。

血红蛋白在它们各自的呼吸器官如肺和胎盘的分压下饱和。

• On oxygenation of hemoglobin, the iron, histidine F8, and linked residues move toward the heme ring. Conformational changes that accompany oxygenation include rupture of salt bonds and loosening of quaternary structure, facilitating binding of additional O2.
在血红蛋白与氧结合的过程中，铁、F8组氨酸及其相连的残基移向卟啉环，同时伴随构象改变，包括盐键断裂和亚基间结合松弛，可促进其它亚基与O2结合。

• 2,3-Bisphosphoglycerate (BPG) in the central cavity of deoxyHb forms salt bonds with the β subunits
that stabilize deoxyHb. On oxygenation, the central cavity contracts, BPG is extruded, and the quaternary structure loosens.
位于脱氧Hb的中央腔的2，3-双磷酸甘油酸与β亚基形成的盐键能稳固脱氧Hb。

在氧合作用中，中央腔收缩，BPG被挤出，且四元结构变得松弛。

• Hemoglobin also functions in CO2 and proton transport from tissues to lungs. Release of O2 from
oxyHb at the tissues is accompanied by uptake of protons due to lowering of the pKa of histidine residues. 在二氧化碳和质子从组织到肺的运输过程中，血红蛋白也起着重要作用。

根据组氨酸Pka值的降低，在组织中氧气从氧合Hb中释放伴随着质子的摄取。

• In sickle cell hemoglobin (HbS), Val replaces the β6 Glu of HbA, creating a ―sticky patch‖ that has a complement on deoxyHb (but not on oxyHb). DeoxyHbS polymerizes at low O2 concentrations, forming fibers that distort erythrocytes into sickle shapes.
在镰刀形红细胞血红蛋白中，正常人血红蛋白β亚基的第6位谷氨酸被缬氨酸所取代，造成了在脱氧Hb上有补体的“粘性碎片”。

镰状细胞血红蛋白在低氧浓度的条件下聚合形成纤维，能将红细胞扭曲成镰刀形状。

• Alpha and beta thalassemias are anemias that result from reduced production of α and β subunits of HbA, respectively.
α和β地中海贫血分别是由成人血红蛋白的α和β亚基的减少引起的贫血症。

CHAPTER TWO
• Nucleic acids contain, in addition to A, G, C, T, and U, traces of 5-methylcytosine,
5-hydroxymethylcytosine, pseudouridine ( ), or N-methylated bases.
核苷酸除了包括A,G,C,T和U外，还含有微量的5-甲基胞嘧啶，5-羟甲基胞嘧啶，假尿苷和N-甲基化碱基。

• Most nucleosides contain D-ribose or 2-deoxy-Dribose linked to N-1 of a pyrimidine or to N-9 of a purine by a β-glycosidic bond.
大多数核苷包含的右旋核糖或D-2-脱氧核糖是通过β-糖苷键与嘧啶的N-1或嘌呤的N-9相连的。

• A primed numeral locates the position of the phosphate on the sugars of mononucleotides (eg, 3′- GMP, 5′-dCMP). Additional phosphoryl groups linked to the first by acid anhydride bonds form nucleoside diphosphates and triphosphates.
一个引物位于磷酸盐在单核苷酸的糖上的位置（如，3′-GMP, 5′-dCMP），额外的磷酰基团通过酸酐键与第一个磷酰基相连形成二磷酸核苷和三磷酸核苷。

• Nucleoside triphosphates have high group transfer potential and participate in covalent bond syntheses. The cyclic phosphodiesters cAMP and cGMP function as intracellular second messengers.
三磷酸核苷拥有很强的集团转移潜能，而且参与共价键的合成。

环状的磷酸二酯环磷腺苷cAMP和环鸟甘酸cGMP可以行使细胞内第二信使的功能。

• Mononucleotides linked by 3′ →5′-phosphodiester bonds form polynucleotides, directional macromolecules with distinct 3′- and 5′- ends. For pTpGpTp or TGCATCA, the 5′- end is at the left, and
all phosphodiester bonds are 3′ →5′.
单核苷酸通过3，5-磷酸二酯键形成多聚核苷酸，多聚核苷酸是拥有清楚的3’和5’端的大分子。

对于序列pTpGpTp或TGCATCA，5’端在左侧，而且所有的磷酸二酯键都是从3’到5’方向延伸。

• Synthetic analogs of purine and pyrimidine bases and their derivatives serve as anticancer drugs either by inhibiting an enzyme of nucleotide biosynthesis or by being incorporated into DNA or RNA.
合成的嘌呤或嘧啶类似物及其衍生物可以作为抗癌药物抑制核苷酸酶的生物合成或整合到DNA或RNA 中。

• DNA consists of four bases—A, G, C, and T— which are held in linear array by phosphodiester bonds through the 3′ a nd 5′ p ositions of adjacent deoxyribose moieties.
DNA包括四种碱基—A,G,C,T—它们通过连接相邻脱氧核糖3’和5’端的磷酸二酯键进行线形排列。

• DNA is organized into two strands by the pairing of bases A to T and G to C on complementary strands. These strands form a double helix around a central axis.
通过碱基A和T、G和C的互补配对，DNA组成了两条链，这两条链围绕中轴形成双螺旋结构。

• T he 3×109 base pairs of DNA in humans are organized into the haploid complement of 23 chromosomes. The exact sequence of these 3 billion nucleotides defines the uniqueness of each individual.
人类的109个DNA碱基对形成单倍体—23条染色体。

30亿个核苷酸精密的顺序决定了每个生物个体的独特性。

• DNA prov ides a template for its own replication and thus maintenance of the genotype and for the transcription of the 30,000–50,000 genes into a variety of RNA molecules.
DNA为自身复制提供模板，因而维持其基因型以及为将30,000–50,000个基因转录成各种RNA分子提供了保障。

• RNA exists in several different s ingle-stranded structures, most of which are involved in protein synthesis. The linear array of nucleotides in RNA consists of A, G, C, and U, and the sugar moiety is ribose.
RNA以不同的单链结构形式存在，其中大部分与蛋白质合成有关。

RNA中核苷酸的线形排列包括A,G,C,U，且其糖基元是核糖。

• The major forms o f RNA include messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). Certain RNA molecules act as catalysts (ribozymes).
RNA的主要形式包括信使RNA （mRNA），核糖体RNA(rRNA)，转运RNA（tRNA）。

某些RNA分子可以作为催化剂（核酶）。

CHAPTER THREE
Enzymes are highly effective and extremely specific catalysts.
酶是具有高效催化作用和极端特异性的催化剂。

• Organic and inorganic prosthetic groups, cofactors, and coenzymes play important roles in catalysis. Coenzymes, many of which are derivatives of B vitamins,serve as ―shuttles.‖Catalytic mechanisms employed by enzymes include the introduction of strain, approximation of reactants,acid-base catalysis, and covalent catalysis.
有机的和无机的辅基，辅助因子和辅酶在催化中担任重要角色。

辅酶担任“运输器”，其中有很多都是维他命B的衍生物。

酶引起的酶催化机制包括引入应变，逼近反应，酸碱催化和共价催化作用。

• Aminoacyl residues that participate in catalysis are highly conserved among all classes of a given enzyme activity.
在所有酶活动中，参加催化反应的氨酰残基都是高度保守的。

• Substrates and enzymes induce mutual conformational changes in one another that facilitate substrate recognition and catalysis.
底物和酶相互引诱对方发生构象改变，促进底物的识别和催化。

• The catalytic activity of enzymes reveals their presence, facilitates their detection, and provides the basis for enzyme-linked immunoassays.
酶的催化活性可以显示它的存在度，促进检出，并为酶联免疫测定提供基础。

• Many enzymes can be assayed spectrophotometrically by coupling them to an NA D(P)+-dependent dehydrogenase.
许多酶通过与NAD(P)相关脱氢酶结合可以被分光光度计测量。

• Assay of plasma enzymes aids diagnosis and prognosis. For example, a myocardial infarction elevates serum levels of lactate dehydrogenase isozyme I1.
血浆酶的测定有利于疾病的诊断和预测。

例如，心肌梗塞可以提高乳酸脱氢酶异构酶I1的血浆水平。

• The study of enzyme kinetics—the factors that affect the rates of enzyme-catalyzed reactions—reveals the individual steps by which enzymes transform substrates into products.
酶的动力学研究影响酶催化反应程度的因素，揭示酶将底物转换为产物的独特过程。

• Reactions proceed via transition states in which ΔGF is the activation energy. Temperature, hydrogen ion concentration, enzyme concentration, substrate concentration, and inhibitors all affect the rates of enzyme- catalyzed reactions.
反应发生经由过渡态，其中ΔGF是活化能。

温度，酸碱度，酶的浓度，底物浓度和抑制剂都能影响酶催化反应的程度。

• A measurement of the rate of an enzyme-catalyzed reaction generally employs initial rate conditions, for which the essential absence of product precludes the reverse reaction.
反应初的速度可以用来衡量酶催化反应的程度，必要产物的缺失可以消除逆反应。

• A linear form of the Michaelis-Menten equation simplifies determination of Km and Vmax.
米-曼氏方程式的线性形式使Km 和 Vmax求解更为简化。

• The effects of competitive inhibitors, which typically resemble substrates, are overcome by raising the concentration of the substrate. Noncompetitive inhibitors lower Vmax but do not affect Km.
竞争性抑制剂与底物相似，通过提高底物的浓度可以减弱它的作用。

非竞争性抑制剂使Vmax减小，但不影响Km。

• The substrates for most enzymes are usually present at a concentration close to Km. This facilitates passive control of the rates of product formation response to changes in levels of metabolic intermediates. 对于绝大多数酶的底物，它的浓度总是接近Km。

这使由代谢中间产物水平的变化引起的产物生成速率的消极控制更加容易。

• Active control of metabolite flux involves changes in the concentration, catalytic activity, or both of an enzyme that catalyzes a committed, rate-limiting reaction.
代谢产物的主动控制涉及浓度的改变，催化活性，或催化定型的限速的反应的酶。

• Selective proteolysis of catalytically inactive proenzymes initiates conformational changes that form the active site. Secretion as an inactive proenzyme facilitates rapid mobilization of activity in response to injury or physiologic need and may protect the tissue of origin (eg, autodigestion by proteases).
催化剂的非活性酶原的选择性蛋白水解导致其构象的改变，形成活性位点。

如果有受伤或生理需要，非活性酶原的分泌物可以促进反应快速进行，从而保护组织（例如，蛋白酶的自身消化）。

• Binding of metabolites and second messengers to sites distinct from the catalytic site of enzymes triggers conformational changes that alter Vmax or the Km.
代谢产物和第二信使结合在不同于酶的催化位点的位置上引起空间构象的改变，进而改变Km 和 Vmax的值。

• Phosphorylation by protein kinases of specific seryl, threonyl, or tyrosyl residues—and subsequent dephosphorylation by protein phosphatases—regulates the activity of many human enzymes. The protein kinases and phosphatases that participate in regulatory cascades which respond to hormonal or second messenger signals constitute a ―bio-organic computer‖ that can process and integra te complex environmental information to produce an appropriate and comprehensive cellular response.
蛋白质的特定丝氨酸、苏氨酸和酪氨酸的残基被蛋白激酶磷酸化和后来的被蛋白质磷酸酶去磷酸化可以调节人体许多酶的活动。

蛋白激酶和磷酸酶共同参与调节级联，组成一个“生物有机电脑”，对激素或第二信使的信号产生应答，“生物有机电脑”可以处理和整合环境中的复杂信息，进而产生合适的综合的细胞应答。

CHAPTER FOUR
Glycolysis is the cytosolic pathway of all mammalian cells for the metabolism of glucose (or glycogen) to pyruvate and lactate. It can function anaerobically by regenerating oxidized NAD+ (required in the glyceraldehyde-3-phosphate dehydrogenase reaction) by reducing pyruvate to lactate.
糖酵解是所有哺乳动物细胞将葡萄糖（或糖原）代谢成丙酮酸盐或乳酸盐的一种胞浆代谢途径。

在无氧条件下，它可以通过将丙酮酸盐还原成乳酸盐再生氧化的NAD+（在甘油醛-30磷酸脱脂酶反应起作用）。

• Lactate is the end product of glycolysis under anaerobic conditions (eg, in exercising muscle) or when the metabolic machinery is absent for the further oxidation of pyruvate (eg, in erythrocytes).
在无氧条件下（例如在肌肉锻炼时）或丙酮酸盐的进一步氧化代谢机制缺乏（例如在红细胞中）时，乳酸盐是糖酵解的最终产物。

• Glycolysis is regulated by three enzymes catalyzing nonequilibrium reactions: hexokinase, phosphofructokinase, and pyruvate kinase.
糖酵解是通过三种催化非平衡反应的酶来调节的，其中包括己糖激酶，磷酸果糖激酶和丙酮酸激酶。

• In erythrocytes, the first site in glycolysis for generation of ATP may be bypassed, leading to the formation of 2,3-bisphosphoglycerate, which is important in decreasing the affinity of hemoglobin for O2. 在红细胞中，产生ATP反应的糖酵解的第一位点可能被旁路替代，导致2,3-双磷脂甘油酸变构酶形成，后者对于降低血红蛋白对氧的亲和力起着重要作用。

• Pyruvate is oxidized to acetyl-CoA by a multienzyme complex, pyruvate dehydrogenase, that is dependent on the vitamin cofactor thiamin diphosphate.
丙酮酸可以被一种叫做丙酮酸脱氢酶的多酶复合体氧化为乙酰基辅酶A，丙酮酸脱氢酶依赖于维生素辅助因子硫胺氯喹。

• Conditions that involve an inability to metabolize pyruvate frequently lead to lactic acidosis.
丙酮酸代谢能力不够会导致乳酸酸中毒。

The citric acid cycle is the final pathway for the oxidation of carbohydrate, lipid, and protein whose common end-metabolite, acetyl-CoA, reacts with oxaloacetate to form citrate. By a series of dehydrogenations and decarboxylations, citrate is degraded, releasing reduced coenzymes and 2CO2 and regenerating oxaloacetate.
糖类、脂类和蛋白质的氧化代谢的最终路径是三羧酸循环，它们最终的共同代谢产物乙酰基辅酶A和丁酮二酸盐反应生成柠檬酸盐。

柠檬酸通过一系列的脱氢和脱羧反应逐级被降解，释放出还原型辅酶和2个CO2 并重新形成丁酮二酸盐。

• The reduced coenzymes are oxidized by the respiratory chain linked to formation of ATP. Thus, the cycle is the major route for the generation of ATP and is located in the matrix of mitochondria adjacent to the enzymes of the respiratory chain and oxidative phosphorylation.
还原型辅酶被与ATP形成相连结的呼吸链氧化。

因此，这个循环是ATP形成的主要的路径，位于线粒体基质中靠近呼吸链酶和与氧化磷酸化相关的酶的位置。

• The citric acid cycle is amphibolic, since in addition to oxidation it is important in the provision of carbon
skeletons for gluconeogenesis, fatty acid synthesis, and interconversion of amino acids.
三羧酸循环是一种双重代谢，除了氧化作用之外，它为糖原异生、脂肪酸合成和氨基酸的变构提供碳骨架。

•Glycogen represents the principal storage form of carbohydrate in the mammalian body, mainly in the liver and muscle.In the liver, its major function is to provide glucose for extrahepatic tissues. In muscle, it serves mainly as a ready source of metabolic fuel for use in muscle.
哺乳动物体内，主要在肝和肌肉中，糖原是糖类的主要储存形式。

在肝脏中，它的主要作用是为肝外组织提供葡萄糖。

在肌肉中，它主要作为肌肉现成的代谢能源供肌肉使用。

• Gl ycogen is synthesized from glucose by the pathway of glycogenesis. It is broken down by a separate pathway known as glycogenolysis. Glycogenolysis leads to glucose formation in liver and lactate formation in muscle owing to the respective presence or absence of glucose-6-phosphatase.
葡萄糖可以通过糖原生成作用合成糖原。

后者可以由糖原分解作用而被破坏。

由于6-磷酸葡萄糖酶的存在或缺乏，糖原分解作用可以分别导致肝中葡萄糖的形成和肌肉中的乳酸盐的形成。

• Cyclic AMP integrates the regulation of glycogenolysis and glycogenesis by promoting the simultaneous activation of phosphorylase and inhibition of glycogen synthase. Insulin acts reciprocally by inhibiting glycogenolysis and stimulating glycogenesis.
环磷腺苷通过同时促进磷酸化酶的激活和糖原合成酶的抑制作用调节糖原分解和糖原生成。

与此相反，胰岛素抑制糖原分解，刺激糖原生成。

• Inherited deficiencies in specific enzymes of glycogen metabolism in both liver and muscle are the causes of glycogen storage diseases.
Gluconeogenesis is the process of converting noncarbohydrates to glucose or glycogen. It is of particular importance when carbohydrate is not available from the diet. Significant substrates are amino acids, lactate, glycerol, and propionate.
在肝脏和肌肉中，糖原代谢的特异性酶的遗传性不足可以导致显得尤为重要。

其重要的底物有氨基酸、乳酸盐、甘油和丙酸盐。

• The pathway of gluconeogenesis in the liver and kidney utilizes those reactions in glycolysis which are reversible plus four additional reactions that circumvent the irreversible nonequilibrium reactions.
肝和肾的糖原异生途径可以充分利用糖酵解中可逆的四个额外反应，后者防止不可逆的非平衡反应的发生。

• Since glycolysis and gluconeogenesis share the same pathway but operate in opposite directions, their activities are regulated reciprocally.
因为糖酵解和糖原异生具有相同的路径但运行的方向却截然相反，它们活动的调节是相反的。

• The liver regulates the blood glucose after a meal because it contains the high-K m glucokinase that promotes increased hepatic utilization of glucose.
饭后，肝可以调节血糖浓度，因为饭后它含有的高K m葡萄糖激酶可以促进肝利用葡萄糖的水平。

• Insulin is secreted as a direc t response to hyperglycemia; it stimulates the liver to store glucose as glycogen and facilitates uptake of glucose into extrahepatic tissues.
胰岛素的分泌作为高血糖的一个直接应答，它刺激肝脏将葡萄糖储存为糖原，并且使葡萄糖易于被肝外组织所摄取。

• Glucagon is secreted as a response to hypoglycemia and activates both glycogenolysis and gluconeogenesis in the liver, causing release of glucose into the blood.
胰高血糖素的分泌作为低血糖的一个反应应答，同时促进肝中的糖原分解和糖原的异生作用，进而将葡萄糖释放到血液中。

• The pentose phosphate pathway, present in the cytosol, can account for the complete oxidation of glucose, producing NADPH and CO2 but not ATP.
在胞质溶胶中存在的戊糖磷酸途径可以引起葡萄糖的完全氧化，产生NADPH和CO2，但不产生ATP。

• The pathway has an oxidative phase, which is irreversible and generates NADPH; and a nonoxidative phase, which is reversible and provides ribose precursors for nucleotide synthesis. The complete pathway is present only in those tissues having a requirement for NADPH for reductive syntheses, eg, lipogenesis
or steroidogenesis, whereas the nonoxidative phase is present in all cells requiring ribose.
这个路径有氧化态和非氧化态之分，氧化态不可逆并产生NADPH，非氧化态可逆并为核苷酸的合成提供核糖前体。

完全通路只是在需要NADPH来还原合成的组织中存在，例如脂肪生成或甾体合成的，然而非氧化态在所有需要核酸糖的细胞中都存在。

• In erythrocytes, the pathway has a major function in preventing hemolysis by providing NADPH to maintain glutathione in the reduced state as the substrate for glutathione peroxidase.
在红细胞中，这个途径通过提供NADPH作为谷胱甘肽氧化酶的底物来维持谷胱甘肽的稳定性，从而防止溶血的发生。

• The uronic acid pathway is the source of glucuronic acid for conjugation of many endogenous and exogenous substances before excretion as glucuronides in urine and bile.
糖醛酸途径是葡糖醛酸的来源途径，作为尿和胆汁中的葡糖苷酸在排泄之前，许多内源性和外源性物质结合。

Chapter 8 Metabolism of Nucleotides
The digestion and absorption of Nucleotides ; the Functions of Nucleotides
I. Nucleotide Biosynthesis
The Biosynthesis of Purines : De novo synthesis pathway; Salvage synthesis pathway
Element source of purine base
Procedure: Synthetic pathway of IMP; Synthesis of AMP and GMP
adenine phosphoribosyl transferase, APRT ; hypoxanthine-guanine phosphoribosyl transferase, HGPRT adenosine kinase ; Thioredoxin reductase
Deoxyribonucleotide Biosynthesis , Analogs of Purine Nucleotide metabolites
The Degradation of Purines: Uric acid
II. The Biosynthesis of Pyrimidines；De novo synthesis pathway; Salvage synthesis pathway
Elememt source of pyrimidine base ; Synthesis of UMP ; Synthesis of CTP ;Synthesis of dTMP /TMP Analogs of Pyrimidine Nucleotide metabolites
The Degradation of Pyrimidines
Deoxyribonucleotide Biosynthesis NDP reduced
Chapter 9 Metabolic Interrelationships and Regulation
The Specialty of Metabolism
1. Entirety ; II、Metabolism regulation
III、Special feature of Metabolism regulation in different tissue
IV、Various kinds of Metabolite posses common metabolic pool
V、ATP is the form of energy
VI、NADPH provides the reducing equivalent for anabolic metabolism
Metabolic Interrelationships
I、Interrelationships in energy
II、Interrelationships of metabolism in three nutrients
Metabolic Specialty and Interrelationships of Tissues and Organs
Liver Heart Brain Muscle Red blood cells Kidney
Regulation of Metabolism
1. Metabolism regulation in cell level: Regional Distribution of Enzymes in Cells •(Compartmentation) key enzyme (limiting velocity enzymes)
•Allosteric regulation of key enzymes--allosteric enzyme---Allosteric effector; feedback inhibition •Chemical modification of enzymes:
•Main types of chemical modification: Phosphorylation and Dephosphorylation
2. Hormone regulation of metabolism
3.Metabolism regulation in relation to the whole
Part III
Genetic Information Transfer : the central dogma
Chapter 10 DNA Biosynthesis (Replication)
Basic Rules of DNA Replication:
semi-conservative replication; bidirectional replication; semi-discontinuous replication
The Enzymology of DNA Replication
Requirements of DNA replication : substrate; polymerase; template; primer ; other Enzymes and Proteins DNA-dependent DNA polymerase(DNA-pol) Properties： 1. Polymerization 5→'3'
2. Exonuclease 3→'5'
3. Exonuclease 5→'3'
Eukaryotic DNA polymerase: DNA-pol αDNA-pol βDNA-pol γDNA-pol δDNA-pol ε
High Fidelity of DNA Replication
Separation of DNA helix and Topology of DNA
Helicase (解螺旋酶) Primase (引物酶) Single-Stranded DNA binding Protein, SSB
DNA Topoisomerase (DNA拓扑异构酶)
DNA Ligase
Process of DNA Replication in E. coli Primosome and Primer
Initiation ; Elongation; Termination
Eukaryotic DNA Replication
Initiation－Cell cycle control replication factor, RF; Proliferation cell nuclear antigen, PCNA Elongation; Termination: Replicating the Ends of Chromosomes---Telomeres are necessary for chromosome maintenance and stability
Telomerase (端粒酶, 126 kD) – an RNA-dependent DNA polymerase - a ribonucleoprotein
Reverse Transcription ; Rolling Circle Replication 滚环复制and D-loop replication D环复制
DNA Damage (Mutation) and Repair
Types of DNA Mutation: mismatch (point mutation ), deletion; insertion ; rearrangement
Frame Shift
Molecular Mechanisms of DNA Repair
光修复(light repair)切除修复(excision repair)重组修复(recombination repair)SOS修复(SOS response)
Chapter 11 Transcription /RNA Biosynthesis
Transcription : The process of RNAs synthesized from DNA templates by RNA polymerase
Requirements of Transcription
Substrates: NTP (ATP, UTP, GTP, CTP) ; Template: DNA; Enzyme: DNA dependent RNA polymerase,
RNA-pol ; Other protein factors
Asymmetric Transcription(不对称转录)模板链(template strand)/有意义链/Watson链
编码链(coding strand, Nontemplate strand / 反义链/Crick链
E.coli RNA Polymerase: holoenzyme ;core enzyme
RNA Polymerase in Eukaryotes :
操纵子(Operon)启动子(Promoter) ：location of transcription start sites, where transcription begins. DNA Footprinting-Identifying the Nucleotide Sequence in DNA where a Protein Binds.
The Process of Transcription
Initiation:1.Binding of RNA Polymerase to DNA template at promoter sites (initiation sites)。

subunit of RNA pol recognizes. ;2. Initiation of polymerization。

（without Primer）Open Promoter Complex
Chain Elongation :Transcription bubble
Chain Termination : Dependent on Rho (ρ) factor ; Non-dependent on Rho (ρ) factor, dependent on termination sites in DNA: Three Structural features in DNA lead to termination: 1. Inverted repeats (C:G-rich), stem-loop structure can form in the transcript; 2. A nonrepeating segment; 3. A run of 6-8 As in the DNA, coding for Us in the transcript.
Transcription in Eukaryotes: cis-acting element ; trans-acting factors : transcription factors, TF have special structure such as zinc finger，helix-turn-helix.
Pre-initiation complex, PIC
Piecing theory, Transcription Termination ---correlative to post-transcriptional modification
Types of Post-transcriptional Modification: splicing ;cleavage ; modification ; addition
Post-transcriptional Processing of mRNA, rRNA, tRNA in Eukaryotic cells
Capping and 3‘-poly A tail Nuclear Pre-mRNA--- hetero-nuclear RNA
snRNA (small nuclear RNA) Small nuclear Ribonucleoprotein
spliceosome
Eukaryotic Genes are Split Genes(断裂基因) Coding region : Exons ; Noncoding region : Introns
RNA Editing---differential RNA processing
Ribozyme; RNA Enzymes, the catalytic RNAs hammerhead structure
Chapter 12 Translation / Protein Biosynthesis
genetic code
During translation, proteins are synthesized on ribosomes by linking amino acids together in the specific linear order stipulated by the sequence of codens in an mRNA.
Protein Biosynthesis System: In Prokaryotes---- Polycistron : In Eukaryotes ---- Single Cistron
open reading frame, ORF
All the codons have meaning: Initiation codon: AUG Termination(nonsense) codons: UAA, UAG, UGA Sense codon: the remaining 61
The Nature of the Genetic Code: 1. Commaless 2. Degeneracy 3. Universal 4. Wobble(Pairing between the third base of the codon and the first base of the anticodon follows less stringent rules )
Amino Acids Activation : Aminoacyl-tRNA Synthetase
Translation start from 5´-AUG of ORF, elongate the polypeptide according to the genetic codon in mRNA and terminate until termination codon.
Protein Biosynthesis direction：N→C .
mRNA, Met-tRNAiMet and ribosome form a translational initiation complex
Peptide chain Initiation in Prokaryotes 1. Separation of 50S and 30S Ribosome, 2. Binding of mRNA in 30S subunit 3. Binding of fMet-tRNAimet into 30S subunit 4. Formation of 70S initiation complex (II）Peptide chain Initiation in Eukaryotes
Elongation factor, EF Entrance ;Peptide bond formation; Translocation
transpeptidase(转肽酶) Release Factor (RF)
Functions of RF: 1.Recognize Termination Codon. RF-1→UAA、UAG；RF-2→UAA、UGA.
2.Convert the transpeptidase activity of the ribosome to hydrolase activity, promote the discharge of
polypeptide. Polyribosome or Polysome(多聚核蛋白体)are the active Structures of Protein Synthesis Posttranslational Processing & Protein Transportation
Newly sythesized polypetides usually undergo structural changes called Posttranslational Processing, and are transported to their final locations where they play physiological roles ----a process called Protein Targeting.
Posttranslational Processing
Folding of newly polypeptides to form special three-dimensional conformations
Modification of protein primary structures
Modification of protein on higher-level structures
I、Folding of newly polypeptides---Some Proteins or Cofactors
1. Molecular Chaperones (分子伴侣)
2. Protein Disulfide Isomerase (PDI、蛋白二硫键异构酶)
3. Peptide Prolyl Cis-trans Isomerase (PPI、肽-脯氨酰顺反异构酶)
Heat Shock Protein / HSP (热休克蛋白) Chaperonins (伴侣素)
PDI has high activity in endoplasmic reticulum (ER, 内质网) , it shuffles the disulfide bonds of the polypeptide and promotes the formation of the correct disulfide bonds that are the most。