2023春Biochemistry （KELI TIAN 田克立）_山东大学

SPOC学校专有课程

2023春Biochemistry （KELI TIAN 田克立）

开课时间： 2023年02月17日 ~ 2023年07月07日

学时安排： 6小时每周

当前开课已结束已有 8 人参加

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spContent=Biochemistry is a discipline that explains the chemical processes within living organisms. It chiefly concerns with the structures, functions and interactions of biological macromolecules and metabolic processes and their regulation mechanism in human body.

Biochemistry is a discipline that explains the chemical processes within living organisms. It chiefly concerns with the structures, functions and interactions of biological macromolecules and metabolic processes and their regulation mechanism in human body.

—— 课程团队

课程概述

COURSE OVERVIEW

Biochemistry is a discipline that studies the living organism at the molecular level, explaining the chemical processes within living organisms. It chiefly concerns with the structures, functions and interactions of biological macromolecules, such as proteins, nucleic acids and metabolic processes and their regulation mechanism in human body. It utilizes the techniques of analytical, organic, inorganic, and physical chemistry in determining the molecular basis of vital processes.

OBJECTIVES

Knowledge

The main objective of the course is to understand structure and function of biomolecules, the metabolism and bioenergetics in human body.

At the end of the course, the student should be able to demonstrate his knowledge and understanding on the:

1. Structural organization and structure-function relationships of proteins and consequences of deviation from normal;

2. Basic and clinical aspects of enzymology and enzyme kinetics;

3. Digestion and assimilation of nutrients;

4. Concepts related to metabolism;

5. Anabolic and catabolic pathways, regulation and physiological roles of carbohydrates;

6. Anabolic and catabolic pathways, regulation and physiological roles of lipids, including triacylglycerols, phospholipids and cholesterol; Metabolism of plasm lipoproteins (CM, LDL, VLDL and HDL) and consequences of deviation from normal;

7. The correlation between energy molecules, reducing equivalents and pathways (Energy metabolism);

8. Catabolic pathways of proteins and amino acids and the relationship between defects in a pathway with certain diseases;

9. Integration of the various aspects of metabolism, and their regulatory pathways;

10. Metabolic characteristics in various tissues and cells, especially in liver and erythrocytes;

11. Principles of various conventional and specialized laboratory techniques and instruments, analysis and interpretation of a given data; experimental design to support theoretical concepts, the physical and chemical properties of biomolecules (protein) used in various studies.

Skills

At the end of the course, the students should be able to

1. Apply conventional techniques/ instruments to perform biochemical analysis

2. Analyze and interpret investigative data

授课目标

OBJECTIVES

The main objective of the course is to understand structure and function of biomolecules, the metabolism and bioenergetics in human body.

成绩要求

EXAM POLICIES

There are eight online unit tests and a final exam given in this course. The final will be comprehensive and will cover materials from the entire course. Exams will be held at 9th week of semester and take place in the computer-based test center. Excused absences will not be given for airline reservations, routine illness (such as colds, flu and stomach aches), or other common ailments without a doctor's note. Excused absences will generally not be given after the absence has occurred, except under very unusual circumstances.

Mark distribution

Online unit tests: 10%

Online discussion: 10%

Assignments: 10%

Final Exam: 50%

Experiments: 20% (attendance + experimental reports)

Total mark: 100 points

课程大纲

Structure and Function of Proteins

课时目标：ObjectivesTo master the molecular composition and structural characteristics of proteins. To understand the structure is the basis of protein functions, and structural changes might cause functional changes, which can be the molecular basis for diseases. To detect the basic physical and chemical properties of proteins, thus to understand the principles of protein separation and analysis methods.

Contents

1 the molecular composition of proteins

1.1 structural characteristics and classification of 20 L-α-amino acids that comprise proteins

1.2 physical and chemical properties of amino acids

1.3 amino acids are linked by peptide bonds to form proteins or active peptides

2 the molecular structure of protein

2.1 primary structure of protein

2.2 secondary structure of protein: peptide unit (plane); the main forms of secondary structure: α-helix, β-sheet and β-turn.

2.3 tertiary structure of protein: motif and domain

2.4 quaternary structure of protein

3 structure-function relationships of proteins

3.1 primary structure is the basis of spatial structure and function of proteins

(1) primary structure is the basis of spatial structure.

(2) proteins with similar primary structure have similar spatial structure and function.

(3) amino acid sequences provide important biological evolution information.

(4) changes in the sequence of key amino acids of proteins can cause diseases, for example, the molecular basis of sickle cell anaemia.

3.2 protein functions depend on their specific spatial structures

(1) structure of myoglobin and hemoglobin.

(2) both the functions of myoglobin and hemoglobin depend on their structures: molecular mechanism of O2 transport and storage: cooperativity and allosteric effect.

(3) protein conformation changes can lead to diseases: prion disease.

4 physical and chemical properties of proteins

4.1 proteins have ampholytic dissociation properties: isoelectric points of proteins.

4.2 the colloidal properties of protein: the factors maintaining the stability of protein in solution arethe surface charge of particles and hydration shell.

4.3 denaturation and renaturation of proteins.

4.4 ultraviolet absorption properties of proteins.

4.5 color reactions of protein: ninhydrin reaction and biuret reaction.

Enzymes

课时目标：ObjectivesTo grasp the molecular composition and structural characteristics of enzyme, concepts of holoenzyme, apoenzyme, cofactors, coenzyme and prosthetic group. To detect the concept of enzyme active center and essential groups. To master the concept and characteristics of isozyme, and understand the clinical significance of isozyme detection. To understand the characteristics of enzyme-catalyzed reaction and the working principle of enzyme. To master the factors that affect the reaction velocity, including substrate concentration, enzyme concentration, temperature, pH, activators and inhibitors, and etc. It is important to understand the Michaelis-Menten equation, the meaning and significance of M-M constant Km and maximum reaction rate Vmax. To grasp the characteristics of competitive inhibitors and understand the mechanism of some antibiotics and anti-tumor drugs. To be familiar with the dynamics of different types of reversible inhibition. To grasp the regulation mechanisms of enzyme activity, such as allosteric regulation, and covalent modification. To grasp the concept and mechanism of zymogen and zymogen activation.

Contents

1 Molecular structure and function of enzyme

1.1 molecular composition of enzymes: including Vitamins.

1.2 active center of enzyme and essential groups of enzyme

1.3 isoenzyme

2 How enzymes work

2.1 characteristics of enzymatic reactions

2.2 enzyme - substrate intercomplex theory

3 Kinetics of enzymatic reaction

3.1 concept of kinetics of enzymatic reaction

3.2 effect of substrate concentration on reaction rate: including M-M equation.

3.3 effect of enzyme concentration on reaction rate

3.4 effect of temperature on the rate of enzymatic reaction

3.5 effect of pH on reaction rate

3.6 effect of inhibitors on enzyme activity

(1) irreversible inhibition

(2) reversible inhibition: including concept, characteristics and dynamics changes of competitive inhibition, non-competitive inhibition and un-competitive inhibition.

3.7 activators

4 Regulation of enzyme activity - rapid regulation 4.1 allosteric enzyme and allosteric regulation

4.2 chemical modification (covalent modification) of enzymes

4.3 zymogen and zymogen activation

5 classification and naming of enzymes (self-learning)

6. Relationship between enzyme and medicine (discussion for after class homework)

Carbohydrate Metabolism

课时目标：ObjectivesTo be familiar with the physiological function, digestion and absorption of carbohydrate. To master the main reaction processes, key enzymes, regulation mechanisms and physiological significances of glycolysis, aerobic oxidation and citric acid cycle. To master the oxidation stage, and the main products of the pentose phosphate pathway and its physiological significance. To master the processes, key enzymes and regulatory mechanisms of glycogenesis and glycogenolysis. To grasp the similarities and differences of muscle glycogen and liver glycogen metabolism. To grasp the concept, the reaction process, key enzymes, regulation mechanism and physiological significance of gluconeogenesis. To master the concept, reaction process and physiological significance of lactate cycle. To master the source and fate of blood glucose, and the regulation mechanism of insulin/glucagon on blood glucose level. To understand the relationship between glucose metabolism disorders and diseases.

Contents

1 Digestion, absorption and transport of carbohydrate

1.1 classification and physiological function of carbohydrates

1.2 digestion, absorption and transport of carbohydrates

(1) digestion process and enzymes

(2) absorption process and mechanism

(3) transport process and the role of GLUT

2 Anaerobic oxidation of carbohydrates

2.1 glycolysis reaction process, key enzymes and energy yield

2.2 regulation mechanism of glycolysis

2.3 physiological significance of glycolysis

3 Aerobic oxidation of carbohydrates

3.1 concept

3.2 three stages of aerobic oxidation

3.3 pyruvate is transported into mitochondria and converted into acetyl CoA

3.4 citric acid cycle: reaction process, key enzymes, energy acquirement and physiological significance

3.5 regulation of aerobic oxidation

4 pentose phosphate pathway

4.1 reaction process

4.2 regulation of pentose phosphate pathway

4.3 physiological significance of pentose phosphate pathway

5 glycogenesis and glycogenolysis

5.1 main organs of glycogen storage and their physiological significance

5.2 glycogenesis

5.3 glycogenolysis

5.4 coordinated regulation of glycogenesis and glycogenolysis

5.5 difference of glycogen metabolism in liver and muscle

6 gluconeogenesis

6.1 concept

6.2 gluconeogenesis pathway and key enzymes

6.3 physiological significance of gluconeogenesis

6.4 lactate cycle and its physiological significance

7 blood glucose

7.1 the sources and fates of blood glucose

7.2 regulation of blood glucose level: hormone regulation

7.3 abnormal blood glucose levels: hypoglycemia, hyperglycemia and diabetes

Lipid Metabolism

课时目标：ObjectivesTo be familiar with the classification and function of lipids. To know about the concept and functions of essential fatty acids. To master the digestion and absorption of lipids and the roles of bile salts and colipase in it. To understand the formation of chylomicron in this process. To master the concept of fat mobilization, its process, key enzymes and regulation mechanism. To master the processes of glycerol metabolism and fatty acid oxidation, the corresponding key enzymes and energy generation. To grasp the concept of ketone bodies, their formation pathway, the utilization sites, the relative catabolic processes and physiological significance. To understand other kinds of oxidation pathways of fatty acids and the important derivatives of unsaturated fatty acids. To master the raw materials, key enzymes and regulation mechanism of fatty acids synthesis. To be familiar with triglyceride synthesis process. To master the synthesis and degradation of glycerophospholipids. To master the raw materials, key enzymes and regulation mechanism of cholesterol anabolism, and the metabolic transformation of cholesterol. To master the classification and composition of plasma lipoproteins, the physiological functions of apolipoprotein, the metabolism processes and key enzymes of the four lipoproteins. To understand the types of hyperlipoproteinemia and dyslipidemia.

Contents

1 Composition, structure and function of lipids

1.1 classification and structural characteristics of lipids

1.2 biological functions of lipids

1.3 fatty acids: essential fatty acids

2 Digestion and absorption of lipids

2.1 digestion of lipids

2.2 absorption of lipids : MG pathway

2.3 transport of absorbed lipids: Chylomicrons

3 metabolism of triglyceride

3.1 catabolism of triglycerides

(1) mobilization of stored triacylglycerol

(2) metabolism of glycerol

(3) oxidation of fatty acids and ATP generation

(4) different types of fatty acids are oxidized in different ways

(5) decomposition of fatty acids in liver can produce ketone bodies: concept; formation pathway and utilization of ketone bodies; physiological significance of ketone bodies; ketonuria and ketoacidosis

3.2 synthesis of triglycerides: sites, raw materials and basic processes 3.3 synthesis of fatty acids

(1) synthesis of palmitate

(2) extension of the carbon chain of palmitate

(3) synthesis of unsaturated fatty acids

(4) regulation mechanism of fatty acids synthesis

4 metabolism of phospholipids

4.1 synthesis of glycerophospholipids

4.2 degradation of glycerophospholipids

5 metabolism of cholesterol

5.1 synthesis of cholesterol: sites, raw materials, key enzyme and regulation mechanism

5.2 metabolic transformation of cholesterol: bile acids, steroid hormones and vitamin D3

6 metabolism of plasma lipoprotein

6.1 blood lipids

6.2 plasma lipoproteins: classification, composition, structure and function

6.3 plasma lipoprotein metabolism: CM, VLDL, LDL and HDL

6.4 plasma lipoprotein metabolism disorders and diseases

Biological Oxidation

课时目标：ObjectivesTo master the concept, composition and sequence of oxidative respiratory chain (electron transport chain), and two electron transport chains: NADH oxidative respiratory chain and FADH2 oxidative respiratory chain. To be familiar with the structure characteristics and electron transfer mechanism of four respiratory chain complexes. To grasp the concepts of substrate level phosphorylation and oxidative phosphorylation. To master the coupling sites and mechanism of oxidative phosphorylation (chemiosmosis hypothesis). To be familiar with the structure, function and mechanism of ATP synthase. To master the key role of ATP in energy conversion, storage and utilization in organism, and the production and physiological significance of creatine phosphate. To master the factors affecting oxidative phosphorylation, including ADP/ATP ratio, inhibitors (such as respiratory chain inhibitors, uncoupling agents and ATP synthase inhibitors), hormones, mitochondrial DNA mutation, and etc. To master the two shuttle systems transporting cytoplasm NADH into mitochondrial To be familiar with the transport of ATP/ADP and inorganic phosphate across the mitochondrial membrane. To be familiar with the production of reactive oxygen species and the antioxidant system (including superoxide dismutase, glutathione peroxidase, catalase, and etc.). To understand the composition and mechanism of cytochrome P450 monooxygenase system.

Contents

1 The oxidative respiratory chain is composed of complexes with electron transport function

1.1 concept and composition of oxidative respiratory chain: respiratory chain complexes and their electron transfer mechanism

1.2 NADH and FADH2 oxidative respiratory chains

2 oxidative phosphorylation and ATP formation

2.1 concept and coupling sites of oxidative phosphorylation

2.2 oxidative phosphorylation coupling mechanism: chemiosmosis hypothesis

2.3 ATP synthesis: structure and catalytic mechanism of ATP synthase

2.4 ATP plays a key role in energy metabolism

3 the effectors on oxidative phosphorylation

3.1 ATP/ADP ratio regulates the rate of oxidative phosphorylation

3.2 inhibitors block the oxidative phosphorylation process

3.3 thyroid hormones promote oxidative phosphorylation and thermogenesis

3.4 the effect of mitochondrial DNA mutation

3.5 selective transport of metabolites across the mitochondrial inner membrane

(1) the shuttle systems for transporting cytoplasm NADH into mitochondria: alpha-phosphoglycerol shuttle and malate-aspartic acid shuttle

(2) ATP-ADP translocation enzymes coordinate the transport of ADP into and ATP out of mitochondria

4 Other oxidation and anti-oxidation systems

4.1 mitochondrial oxidative respiratory chain can also produce reactive oxygen species

4.2 antioxidant enzyme system has the function of scavenging reactive oxygen species: such as catalase, glutathione peroxidase, superoxide dismutase, and etc.

4.3 microsomal cytochrome P450 monooxygenase catalyzes hydroxylation of substrate molecules

Digestion and Absorption of Protein and Amino Acids Metabolism

课时目标：ObjectivesTo grasp the concept and types of nitrogen balanceand essential amino acids. To understand the nutritional value of protein. To grasp the digestion and absorption processes of proteins. To be familiar with the functions of various enzymes in protein digestion. To master the concept of protein putrefaction and its products. To be familiar with the way of protein degradation in eukaryotic cells, amino acids metabolic pool and alpha-ketoacid metabolism. To master the ways of amino acid deamination, including amino transformation, L-glutamic acid oxidative deamination, associated deamination, and etc. To master the sources, fates and transport of ammonia. To master the process and sites of urea production (ornithine cycle). To understand the regulation mechanism of urea synthesis. To be familiar with amino acid decarboxylation, which can generate the active physiological substances. To master the concept, carrier and physiological function of one carbon units. To master the formation way of active methyl group. To be familiar with the process of methionine cycle and creatine synthesis. To master the active physiological substances produced from phenylalanine and tyrosine. To understand the relationship between abnormal amino acid metabolism and diseases.

Contents

1 nutritional value, digestion and absorption of protein

1.1 nitrogen balance

1.2 nutrient essential amino acids determine the nutritional value of proteins: essential amino acids

1.3 exogenous proteins are digested into amino acids and oligopeptides and then absorbed

1.4 putrefaction of undigested proteins occurs in the lower segment of the large intestine

2 general metabolism of amino acids

2.1 protein decomposition to produce amino acids: two important pathways of intracellular protein degradation, including the lysosome pathway and the ubiquitin-dependent proteasome pathway

2.2 exogenous and endogenous amino acids constitute the amino acid metabolism pool

2.3 metabolism of amino acid carbon skeletons

2.4 deamination of amino acids: transamination, L-glutamate dehydrogenase catalytic oxidative deamination and associated deamination.

3 ammonia metabolism

3.1 sources of serum ammonia in the body

3.2 ammonia is transported in the form of alanine and glutamine in the blood circulation

3.3 synthesis of urea in liver is the main metabolic fate of ammonia

(1) ornithine cycle: metabolism process, key enzymes, regulation and physiological significance

;(2) the disorder of urea synthesis can cause hyperammoniasis and ammonia poisoning

;4 metabolism of individual amino acids

4.1 decarboxylation of amino acids

4.2 one carbon unit

4.3 sulfur-containing amino acid metabolism

4.4 aromatic amino acid metabolism

4.5 metabolism of branched chain amino acids

Integration and Regulation of Metabolism

课时目标：ObjectivesTo be familiar with the characteristics of metabolism, and master interconnection and integration of the major metabolic pathway and energy metabolism. To master the regulation mechanism of metabolism, including the concept, significance and characteristics of key enzymes, and the allosteric regulation and chemical modification of enzymes. To be familiar with the metabolic characteristics of main tissues and organs. To be familiar with the general regulation in different conditions, such as fasting, starvation and stress. To understand the metabolic characteristics of obesity.

Contents

1 interconnection and integration of metabolism

1.1 various metabolic processes in the body are connected as a whole

1.2 metabolism and energy metabolism are interrelated

1.3 metabolism of carbohydrates, lipids and proteins are related to each other through intermediate metabolites

2 Mechanism of metabolic regulation

2.1 regulation at the cell level: regulation of key enzymes

2.2 hormones regulate target cell metabolism through specific receptors

2.3 the body coordinates overall metabolism through the nerve-humoral system

3 Metabolic characteristics of important tissues and organs in the body

3.1 liver is the center and hub of metabolism

3.2 the brain mainly uses glucose for energy and oxygen consumption

3.3 the myocardial cells can get energy from a variety of substances

3.4 muscle glycogen and fatty acids are the main energy sources of skeletal muscle

3.5 adipose tissues are important for storing and mobilizing of triglycerides

3.6 the kidney may undergo gluconeogenesis

4 the general regulation in different conditions

4.1 fasting

4.2 starvation

4.3 stress

5 the metabolic characteristics of obesity

Biochemistry of the Blood

课时目标：ObjectivesTo understand the classification, properties and functions of plasma proteins. To master the synthesis of heme, including raw materials, key enzymes and main processes. To be familiar with the regulation of heme synthesis. To master the characteristics of erythrocyte metabolism.

Contents

1 plasma proteins

1.1 classification and properties of plasma proteins

1.2 functions of plasma proteins

2 heme biosynthesis

2.1 heme biosynthesis: raw materials, processes and key enzymes

2.2 regulation of heme synthesis

3 Blood cell metabolism

3.1 erythrocyte metabolism

3.2 leukocyte metabolism

Biochemistry of the Liver

课时目标：ObjectivesTo master the structure characteristics of liver and its role in metabolism. To grasp the concept and significance of biotransformation in liver, and the types of biotransformation reactions. To be familiar with the factors affecting biological transformation. To be familiar with the classification of bile acids. To master the metabolism and functions of bile acids in human bodies. To master the formation, transport and metabolism of bile pigment. To master the concept and characteristics of free bilirubin and conjugated bilirubin. To be familiar with bile pigment enterohepatic circulation. To understand abnormal metabolism of bile pigment and jaundice, and to understand the biochemical changes of different types of jaundice.

Contents

1 Role of liver in metabolism

1.1 liver is an important organ to maintain a relatively stable blood glucose level

1.2 liver plays an important role in lipids metabolism

1.3 protein synthesis and catabolism in liver are very active

1.4 liver is involved in the metabolism of various vitamins and coenzymes

1.5 liver is involved in inactivation of various hormones

2 Biotransformation in liver

2.1 biotransformation: concept, sites and significance

2.2 main reaction types of biotransformation:

(1) the first class reaction, including oxidation, reduction and hydrolysis reactions

(2) the second class reaction: conjugation reaction

2.3 biotransformation is influenced by many factors

3 Metabolism of bile and bile acids

3.1 classification of bile acids

3.2 physiological functions of bile acids

3.3 metabolism of bile acids and enterohepatic circulation of bile acids

4 Metabolism of bile pigment and jaundice

4.1 bilirubin production: the source, sites and process of bilirubin formation

4.2 bilirubin is mainly transported by binding with albumin in the blood

4.3 metabolic transformation of bilirubin in liver: uptake, transport, binding products and excretion

4.4 metabolic changes of bilirubin in intestinal tract and enterohepatic circulation of bile pigment

4.5 hyperbilirubinemia and jaundice

EXPERIMENTS

课时目标：Basic Knowledge and Skills1. Introductionof biochemistry lab and the safety aspects2. Laboratory Instrumentation3. Use of instruments and pipettes

Unit 1: Quantitative analysis of proteins

1. Spectrophotometry

(1) Lambert-Beer's law

(2) principle, working methods and applications of spectrophotometers

(3) measurement of absorption spectra and calculation

2. Experiments involving qualitative analysis by spectrophotometric method

(1) Estimation of total protein by Biuret method

(2) Estimation of total protein by Coomassie brilliant Blue binding method

(3) Estimation of total protein by Ultraviolet absorption method

Unit 2: Separation and purification of serumγ-globulin

1. Chromatography: principle,category, applications and technique of gel chromatography and ion-exchange chromatography

2. Experiment: separation and purification of serumγ-globulin by salt precipitation, gel chromatography and ion-exchange chromatography

Unit 3: Centrifugation, electrophoresis and metabolic experiments

1. Electrophoresis: principle, working methods and applications, and the main point is agarose gel electrophoresis

2. Centrifugation: principle, working methods and applications

3. Experiments

(1) Cellulose acetate membrane electrophoresis of γ-globulin and serum proteins.

(2) Estimation of serum cholesterol

(3) Identification of glycolysis intermediate product

展开全部

预备知识

Biology, Organic Chemistry

参考资料

LEARNING RESOURCES

1. Lehninger Principles of Biochemistry. Ed. Lehinger, Nelson and Cox. W.H. Freeman and Company, New York.

2. Lippincott’s Illustrated Reviews: Biochemistry. Denise R.Ferrier,Wolters Kluwer.

3. Biochemistry Ed. Lubert Stryer. W.H. Freeman and Company, New York.

4. Harper”s Biochemistry, Ed. R.K. Murray, D.K. Granner, P.A. Mayes and V.W. Rodwell. Appleton and Lange, Stamford, Connecticut.

5. Textbook of Biochemistry with Clinical Correlations. Ed. Thomas M. Devlin, Wiley-Liss Publishers.

6. PowerPoint images are available through the class blackboard site

7. Individual meetings with the instructor are encouraged.

TEACHING-LEARNING METHODOLOGIES

Apart from the conventional black board teaching, other modes of teaching that will be adopted are power points, problem solving, and group projects.

Assignments will be designed such as students inculcate the habits of reading reference books and science journals.

常见问题

Statements:

1. Some pictures, animations and videos of this course come from the web, which can be used for teaching. If your rights are violated, please contact us.

2. Please respect your teachers and classmates and be kind to others.

3. Please do not post illegal or prohibited information on the platform.