Elaborate Course: Biochemistry

精品课程：生物化学

Syllabus

(TENTATIVE)

Course Title:  Biochemistry

Course Code: 11013230

Majors: MBBS

Total hours: 80

Lectures: 80

Credits: 5

Affiliation: Medical School, Southeast University

Syllabus created by: Liudi Yuan, PhD       email: yld@seu.edu.cn, tel: 83272474

1. Course Description

Biochemistry studies the molecules and chemical reactions in organisms, trying to understand the nature of life at the molecular level. It focuses on the structures and functions of macromolecules, metabolism, and the molecular mechanisms of gene expression and regulation. Biochemical research mainly uses the principles and methods in chemistry, as well as biophysics, physiology, cell biology, genetics and immunology. The studies of structures and functions of nucleic acids and proteins, gene expression and regulation are also called molecular biology, which is an imp ortant part of biochemistry. With the development of modern molecular biology, we has discovered that life is highly ordered and consistent. Molecular biology research has made great progresses theoretically and practically. Biochemistry has become the common language of life science and the frontier research field.

Medical biochemistry mainly focuses on human body, but studying human body directly has many limitations and difficulty. Thus, the basic knowledge and theories in this course are based on the researches from microorganism, animals and plants. In fact, recent biochemical research has accumulated a lot of knowledge about human metabolism and diseases. Meanwhile, clinic practice has also gain huge amounts of biochemical materials, which greatly promote the development and application of biochemistry.

Biochemistry is one of the obligatory basic medical courses for medical students. In this course, we will discuss the biochemical processes under both physical and pathological conditions of human. We have seen more and more applications of biochemistry and molecular biology in modern medicine. It has been the important goal of modern biomedical research to illustrate the mechanism of diseases at the molecular level and find new treatment for diseases. Understanding biochemistry and the molecular mechanism of human physiological processes will be a great help for further medical courses.

2. Contents and Requirement

Introduction

Goals:

Understand

• Definitions of biochemistry and molecular biology

• Importance of biochemistry and molecular biology in basic and clinic medicine

Contents:

• Definition of biochemistry and molecular biology

• Importance of biochemistry and molecular biology in basic and clinic medicine

• Organization of the course and learning tips

Section I Structure and Function of Macromolecules

Chapter 1 Protein Structure and Function

Goals:

Master

• Average nitrogen content;

• Names, abbreviations, chemical structures and categories of 20 common amino acids

• Covalent and non-covalent bonds in proteins

• Primary and tertiary structure (conformations) of proteins

• Physico-chemical properties of proteins: amphoterism, isoelectric point, high polymer, precipitation, absorbance, color reactions, denaturation.

Understand

• Molecular Chaperon

• Relation between conformation and function,

• Relation between primary and tertiary structure

• Individual difference in primary structure and diseases

Know

• Separation and purification of proteins

• Protein classification

Contents:

• Chemical elements in proteins

• Amino acids, abbreviations, R groups, modified amino acids, peptide bond, main chains and side chains of polypeptides, N-terminus, C-terminus, representation of polypeptides

• Primary, secondary and 3D structures of proteins. 

• Conformation: main chain and side chain

• Domains, molecular chaperon and motifs

• Tertiary structure, protein assembly and recognition

• Relation between structure and function: protein conformation and disease; denaturation;  alleric regulation; individual difference in primary structures and diseases

• Chemical and physical properties of proteins: amphoterism; isoelectric point; high polymer; precipitation; absorbance; color reactions; denaturation

• Protein classifications based on symmetry, solubility, structure and function

Chapter 2 Structure and Function of Nucleic Acid

Goals:

Master

• Chemical components and structure of nucleotides

• Structure of cyclic nucleotides

• DNA primary, secondary and tertiary structure

• Double helix of DNA

• Types of RNAs

• RNA primary and secondary structure, tRNA tertiary structure

• Physico-chemical properties of DNA and RNA

Understand

• Small RNA and RNomics

• Superhelix and nucleosome

Know

• Ribozyme

Contents:

• Components and structures of nucleosides, nucleotides and cyclic nucleotides

• Structures of DNA: base groups; primary, secondary and tertiary structures; double helix; superhelix; nucleosome; linear and cyclic DNA; types of DNA double helixes

• Structures of RNA: base groups; primary, secondary structures; tRNA tertiary structures and functions; types of RNAs; small RNAs and RNomics

• Chemical and physical properties of DNA and RNA: molecular weight; denaturation

Chapter 3 Enzymes

Goals:

Master

• Concept and mechanism of enzymes: catalytic efficiency, specificity, instability, and its regulation.

• Concept of ribozyme

• Structures and catalytic functions of enzymes: apoenzymes, cofactors, Vitamin B coenzyme, holoenzyme, essential groups, active sites

• Activation of zymogen

• Concept of isoenzyme

• Kinectics of enzyme-catalyzed reactions

• Activation and inhibition of enzymes

• Types of inhibition and their characteristics

• Allosteric enzymes

Understand

• Factors that affect the catalytic activity of enzymes

Know

• Catalytic mechanism of enzymes

• Classification of enzymes

• Relation between enzymes and medicine

Contents:

• Concept of enzymes

• Characteristics of enzymes:

• Structure of enzymes and the catalytic center

• Components of enzymes

• Concepts of apoenzyme, holoenzyme, coenzyme and cofactor

• Concept of active site

• Zymogen activation

• Concept of isoenzyme

• Concept of allosteric enzyme

• Vitamin B and coenzyme

• Catalytic mechanism of enzymes: activation energy, enzyme-substrate transition state, induced-fit model

• Kinetics of enzyme-catalyzed reaction: concepts, initial reaction rate, effect of enzyme and substrate concentrations on reaction rate, Michaelis-Menten equation, Km, measurement of Vmax and Km, effects of temperature and pH on reaction rate

• Activators and inhibitors

• Modified enzymes

• Nomenclature and classification of enzymes

• Applications: relations between enzymes and diseases. Secretion of enzymes from damaged cells; secretion defect; enzymes used as diagnosis and treatment for diseases.

Section II Metabolism

Chapter 4 Carbohydrate Metabolism

Goals:

Master

• Concepts of carbohydrate metabolism: key enzymes, energy exchange and regulation.

• Physiological significance of each metabolic pathway

• Whole process of aerobic oxidation

Understand

• Glycogenesis and glycogenolysis

• Glyconeogenesis

• Connection and dynamic balance between carbohydrate metabolic pathways

• Generation and regulation of blood sugar

Know

• Physiological importance of carbohydrates

• Pentose phosphate pathway

• Disorders of l blood sugar and glucose tolerance

Contents:

• Overview of carbohydrate metabolism

• Glycolysis: key enzymes; energy generation and utilization; regulation and physiological significance

• Aerobic oxidation. Three steps: i) generation of pyruvate; ii) pyruvate to acetyl-CoA in mitochondrion (pyruvate dehydrogenase complex and cofactors) ;iii) tricarboxylic acid cycle (acetyl-CoA, CO2, and NADH). Generation of ATP during aerobic oxidation. Physiological significance of aerobic oxidation.

• Pentose phosphate pathway. Two steps: i) oxidative branch: generation of NADPH and pentose phosphate; ii) non-oxidative branch: glucose-6-phosphate dehydrogenase, group transfer. Regulation and physiological significance of this pathway

• Glycogen metabolism: glycogenesis and glycogenolysis. Enzyme-catalytic reactions, UDPG production, glycogen synthase and phosphorylase. Regulation and its importance.

• Glyconeogenesis: key enzymes, regulation and significance.

• Blood sugar: source and usage, concentration, regulation and glucose tolerance test.

Chapter 5 Lipid Metabolism

Goals:

Master

• Essential fatty acid

• Fat mobilization and function of hormone-sensitive triglyceride lipase

• β-oxidation of fatty acids: production of acetyl-CoA, NADH and FADH; energy exchange

• Oxidation of fatty acids in liver: production, utilization and importance of ketone bodies

• Synthesis of fatty acids: materials, hydrogen provider, key enzymes and regulation

• Lipid

• Phospholipid: classification, components, degradation and synthesis

• Cholesterol: synthesis: key enzymes and regulation. Metabolism of cholesterol and the physiological functions of its metabolites

• Plasma lipids: types, generation and characteristics. Metabolism of lipoproteins.

Understand

• Production of chylomicrons.

• Synthesis of lipid

• Metabolism of unsaturated fatty acids and production of prostacyclin, thromboxane and leukotriene

Know

• Metabolism of sphingolipids

• Plasma lipoprotein metabolism and disorders

Contents:

• Production of chylomicrons

• Lipid mobilization, fatty acid activation, acyl-CoA transportation, β-oxidation. Palmitic acid oxidation. Saturated fatty acid oxidation. Other oxidation pathways. Formation, types and characteristics of ketone bodies. Oxidation of ketone bodies.

• Synthesis of fatty acids: synthesis sites, materials. Key steps: malonyl-CoA formation; acetyl-CoA carboxylase, function of ACP. Fatty acid synthase. Elongation of fatty acid chain. Synthesis of unsaturated fatty acids. Essential fatty acids. Synthesis of lipid. Oxidation of polyunsaturated fatty acids. Metabolites of polyunsaturated fatty acids: prostacyclin, thromboxane and leukotriene

• Phospholipid: classification, components, function, degradation and synthesis

• Cholesterol: synthesis: materials, key enzymes and regulation. Metabolism of cholesterol and the physiological functions of its metabolites

• Lipoproteins: definition, classification, characteristics and function. Lipoprotein and plasma lipid. Plasma lipoproteins: ultracentrifugation separation and classification. Types and functions of apolipoprotein. Hyperlipidemia definition and classification.

Chapter 6 Biological Oxidation

Goals:

Master

• Concept of biological oxidation, characteristics and importance

• Electron transfer chain in mitochondrion: oxidative phosphorylation. Generation of ATP and P/O value. Other high energy chemicals

• Respiratory chain inhibitors and uncoupling agents.

Understand

• Other oxidative pathways

• Catalase, peroxidase

• Chemiosmotic hypothesis

• Malate-aspartate shuttle and glycerol phosphate shuttle

• Enzymes in microsome

Know

• Oxidative phosphorylation coupling

Contents:

• Definition of biological oxidation and oxidative phosphorylation: characteristics, importance and high energy phosphate compound. Pathways of biological oxidation and enzymes

• Oxidation system in mitochondrion: components of respiratory chain and their functions: flavin, iron-sulfur protein, ubiquinone, cytochromes, porphrin. Orders of respiratory chain complexes: NADH oxidative respiration chain, succine acid oxidation. Electron transfer chain. Definition and function of oxidative phosphorylation. Coupling sites, P/O value. Chemiosmotic hypothesis. ATP synthase. Factors that affect oxidative phosphorylation: inhibitors and uncoupling agents.

• Oxidase in microsome: mixed function oxidase, oxidase in peroxisome. Superoxide dismutase function.

Chapter 7 Amino Acid Metabolism

Goals:

Master

• Nitrogen balance, complementary effect and protein nutrition value

• Transamination, oxidative deaminization, transdeamination, purine nucleoride cycle

• α-keto acid metabolism

• Origin and catabolism of blood ammonia: transportation of ammonia and major catabolic pathway

• Ornithine cycle (urea cycle): enzyme-catalyzed reactions of urea synthesis, importance of urea

• Metabolites of amino acids: histamine, ᵞ- aminobutyric acid and 5-hydroxytryptamine

• Tetrahydrofolic acid transported one carbon units: names and physiological functions

• Functions of creatine phosphate, S- ademetionine, PAPS and polyamine etc

Understand

• Metabolism of sulfur amino acid, aromatic amino acid and its biological function

• Catabolism of branched chain amino acids

• Relationship and connection of protein, carbohydrate and lipid metabolism

Know

• Digestion of proteins and absorbance of amino acids

• Transformation and regeneration of protein in the body

• Mechanism of transamination. Hyperammonemia and ammonia poisoning

Contents:

• Nutrition of proteins. Nitrogen balance. Physiological functions and nutrition value of proteins. Digestion, absorbance, and putrefaction

• Introduction of metabolism of amino acids. Transformation and regeneration of proteins in body. Origin and catabolism of blood amino acids. Concentration of blood amino acids.

• General metabolism of amino acids. Concept of transamination; transaminase catalyzed reaction, function of pyridoxal phosphate. Oxidative deamination. Transdeamination. purine nucleoride cycle. Non-oxidative deamination. Transformation of ammonia and carbon skeleton.

• Metabolism of ammonia. Dynamics of blood ammonia, transportation of ammonia and ornithine cycle. Urea synthetase, significance of urea synthesis. Other metabolism pathways of ammonia. Degradation and transformation of amino acids.

• Decarboxylation of amino acids, transformation of histine to histamine, glutamic acid to ᵞ-aminobutyric acid, tryptophan to 5-hydroxytryptophan.

• Metabolism of one carbon unit. Concept, origin and type, interaction with tetrahydrofolic acid.

• Metabolism of sulfur amino acids. Function and significance of creatine and creatine phosphate.

• Metabolism of aromatic amino acids: metabolism of phenylalanine and catecholamine, production of thyroxine and transformation of tryptophan.  

• Metabolism of branched amino acids.

Chapter 8 Biochemistry of Blood

Goals:

Master

• Classification and properties of plasma proteins, functions of important plasma proteins

• Synthesis of Heme

• Characteristics and function of carbohydrate metabolism in blood red cells, ratio of albumin and globulin

Understand

• Regulation of Heme synthesis

• Carbohydrate metabolism pathway in blood red cells

• Redox system

Know

• Components of plasma proteins

Contents:

• Classification and properties of plasma proteins, functions of important plasma proteins

• Metabolism in blood red cells : synthesis of Heme and regulation; function of folic acid and vitamin B6 in heme synthesis. Characteristics of mature red cells: glycolysis; 2,3-BPG pathway and its importance. Function of pentose metabolism, NADPH, GSH, NADH in red cells

Chapter 9 Biochemistry of Liver

Goals:

Master

• Functions of liver in carbohydrate, lipid and protein metabolism

• Importance of liver biotransformation. Function of mixed function oxidase

• Origin, types and excretion of bile acids. Enterohepatic circulation of bile acid. Functions of bile salts.

• Catabolism of heme: origin and transport of bilirubin; absorbance and transformation of unbound bilirubin in liver; transformation and excretion of bilirubin in intestinal tracts, bilinogen enterohepatic circulation; urobilinogen and urobilin

Understand

• Biotransformation reactions

• Synthesis of bile acids

Know

• Metabolism of bile pigment and jaundice

Contents:

• Functions of liver in metabolism: functions of liver in carbohydrate, lipid and protein metabolism

• Function of biotransformation: concept, types and characteristics of biotransformation, influencing factors

• Bile acid metabolism: production of primary bile acid in liver, production of secondary bile acid, excretion of bile acid and enterohepatic circulation of bile acid. Biological functions of bile acids

• Metabolism of bile pigment: origin of bile pigment, production of bilirubin, spatial conformation of bilirubin, transportation of bilirubin, properties of unconjugated bilirubin, transformation of bilirubin, absorbance of unconjugated bilirubin,  production and properties of bilirubin glucuronide. Transformation and excretion of bilirubin in intestinal tracts, bilinogen enterohepatic circulation. Urobilin and jaundice.

Section III Information Pathways

Chapter 10 Nucleotide Metabolism

Goals:

Master

• Purine ribonucleoride de novo synthesis: materials and energy; procedures of nucleotides synthesis; production of IMP and its transformation to AMP and GMP

• Pyromidine ribonucleotride de novo synthesis: key enzymes, product UMP and its transformation to CTP, production of TMP

• Deoxynucleotide synthesis: synthesis of NTP, regulation

• Metabolites of purine and pyromidine

Understand

• Salvage pathway of nucleoride synthesis

• Concept and function of antimetabolite

Know

• Uric acid and gout

• Mechanism of antimetabolite

Contents:

• Metabolism of purine ribonucleoride. Synthesis: de novo synthesis; generation of IMP and its transformation into AMP and GMP. Salvage pathway: influencing factor. Catabolism of purine ribonucleoride: generation of uric acid and introduction of gout.

• Metabolism of pyromidine ribonucleoride. Synthesis: generation of UMP and its transformation into CTP; generation of TMP. Salvage pathway: influencing factors. Catabolism of pyromidine and its products.

• Synthesis of deoxynucleoride: reaction system; mechanism of ribonucleoride reductase. Synthesis of deoxyadenylic acid, NTP, dNTP.

• Concept, mechanism and clinic significance of antimetabolite.

Chapter 11 DNA Biosynthesis

Goals:

Master

• Central dogma

• Semiconservative replication of DNA: process, enzymes and factors

• Biological significance of DNA synthesis

• Concept and process of reverse transcription

Understand

• DNA synthesis in eukaryotes

• Experimental evidence of semiconservative replication

• Concept of telomerase

• DNA damage and repair

Know

• Rolling circle replication

• D ring replication

• Mechanism of telomerase

Contents:

• Mechanism of DNA replication: experimental evidence for semiconservative replication hypothesis

• DNA synthesis in prokaryotes: enzymes and factors, eg DNA polymerases, helicase, ligase, primase etc. Process of replication: initiation, elongation, termination.

• DNA synthesis in eukaryotes: basic concepts, telomerase

• Reverse transcription: basic concepts, process, reverse transcriptase

• Rolling circle replication and D ring replication

• DNA damage and repair: physical and chemical causes. Types of DNA repair and the enzymes involved.

Chapter 12 RNA Biosynthesis

Goals:

Master

• Mechanism and process of RNA transcription in prokaryotes: template strand and coding strand. Initiation of RNA transcription, components and functions of RNA polymerase, promoter. Elongation and termination of RNA transcription

• RNA post-transcriptional processing and modification in eukaryotes

• Ribozyme: basic concept, characteristics and significance

Understand

• Processing and modification of tRNA and rRNA

• Eukaryotic RNA polymerase

• RNA replication

Know

• RNA transcription process in eukaryotes

Contents:

• RNA transcription template: template strand and coding strand

• Prokaryotic RNA polymerase: subunits, core enzyme, σ factor, holoenzyme

• Process of prokaryotic RNA transcription: initiation (promoter recognition of RNA polymerase holoenzyme via σ factor, replication origin, promoter); elongation (direction, formation of phosphate diester bond, interactions between holoenzyme and σ factors); termination (terminator sequence, ρ factor).

• Eukaryotic RNA polymerases: types and functions. Transcription factors, transcription process and characteristics

• Posttranscriptional processing: basic concept; mRNA, tRNA and rRNA processing. Difference of processing between prokaryotes and eukaryotes.

• Ribozyme: concept, characteristics.

• RNA replication

Chapter 13 Protein Biosynthesis

Goals:

Master

• Protein translation machinery

• Characteristics and functions of three types of RNAs

• Function of aminoacyl-tRNA synthetase

• Formation of prokaryotic 70S initiation complex

• Ribosome cycle

Understand

• Elongation of peptide and elongation factors

• Termination of translation and polyribosome cycle

• Posttranslational processing and modification

• Interfering and inhibition of protein translation

Know

• Characteristics of eukaryotic protein translation

• Protein targeting

Contents:

• System of protein translation: mRNA and genetic codon, characteristics of genetic codon, initiation codon, termination codon, mitochondrion genetic codon, aminoacyl-tRNA, anticodon and complementary mRNA. Assembly of ribosome and rRNA, 30S and 50S ribosome subunits.

• Protein translation: formation and translocation of aminoacyl-tRNAs. Initiation (initiation complex, initiation factors), elongation (registration, peptidyl transferase and translocation, elongation factors), termination of protein translation, release of newly synthesized proteins. Polyribosome cycle.

• Comparison of prokaryotic and eukaryotic protein translation: initiation complex, rRNA, recognition of initiation codon, initiation factors, components of ribosome, elongation factors and termination factors.

• Posttransloational processing and modification: protein targeting, signal peptide.

• Interfering and inhibition of protein translation: antibiotics, toxins and interferon.

Section IV

Chapter 14 Genetic Engineering

Goals:

Master

• Concepts of DNA recombination and genetic engineering, basic technical procedures

• Types and applications of tool enzymes

• Vectors, targeting genes and construction of recombinant DNA, transformation, selection, amplification and verification

• Medical applications of recombinant DNA and gene engineering

Understand

• Principles of gene diagnosis and therapy

• Nucleic acid hybridization and DNA library

Know

• Relation between recombinant DNA and medicine

Contents:

• Concepts of genetic engineering. Types and functions of tool enzymes. Gain of vectors and target genes, construction of recombinant DNA, transformation, selection, amplification and verification.

• Relationship between recombinant DNA and medicine: discovery of disease genes, DNA diagnosis, gene therapy and prevention of genetic diseases

• Development of gene engineering products

• Chapter 15 PCR

Distribution

ASESSMENT:

Final mark＝attendance＋midterm exam＋experiment mark＋final paper exam

Attendance: 10%

Midterm exam: 30%

Experiment mark: 20%

Final paper exam: 40%

Textbooks and reference

1. Jia Hong-Ti. Biochemistry. People’s medical publishing house，2007

2. Murray Robert et al. harper’s illustrated biochemistry. Mc Graw Hill. 29th editions.

3. P.C. Turner, A.G. Mclennan, A.D. Bates & M.R.H. White, Instant Notes in Molecular Biology, 2^nd edition, Bios scientific publishers limited, 2002.