BIOCHEMISTRY Enzymes & Metabolism Dr. Xuemin Wang E. Desmond Lee Endowed Professor Dept of Biology University of Missouri, St. Louis, MO 63121 http://www.umsl.edu/~biology/faculty/w ang.html
Member & PI Donald Danforth Plant Science Center, St. Louis Donald Danforth Plant Science Center http://www.danforthcenter.org/wang Email: swang@danforthcenter.org
Fascinating Facets of
LIPIDS 2008 summer
LIPID Functions in Plants: Lipids are Vital to Solar Energy Capture, Carbon Fixation, Plant Growth, & Response to the Environment
Sun Sun
Cellular membran es Photosynth etic pigments, vitamins, antioxidants Protecti ve & structur al
Essential oils that attract pollinators or repel predators Growth regulators (e.g. JA, BR)
Wang Lab Research Focus:
Projects: Lipid-Mediated Cell Signaling Networks
Enabling Technology: Lipidomics
Phospholipases & Lipid Turnover
Metabolic Engineering & Crop Improvement
Applications: Bioenergy Oil & Biomass
Drought water use efficiency
Arabidopsis
Support:
NSF (IOS, CMB, MRI)
DOE (EFRC, ARPA-E) USDA, DOT/NBB
Nutrition N & Pi use efficiency
Camelina
Course Objectives: •
Become biochemically literate
• Lay a solid foundation of biochemistry for preparing students for in-depth study of various fields of biochemistry, cell biology, molecular biology, physiology, etc • Be familiar with exciting developments of modern biochemistry
Reference TEXTBOOK:
Fundamentals of Biochemistry (4ed, 2013) Voet/Voet/Pratt
Course Materialwill deal mostly with subject matter covered in the lecture and assigned reading. Problems will be assigned to each lecture to enhance the learning, but they will not be collected or graded. Students are responsible for the material covered in the class lectures, assigned readings, and problems.
1970
1980
1990
2000
Lehningerian idealism Metabolomics realism
Genomic sequencing Enzyme sloppiness
Overlooked organic chemistry
All biological compounds are subjected to the same organic chemistry
2010
Overview of Metabolism
1970
1980
1990
2000
Lehningerian idealism Metabolomics realism
Genomic sequencing Enzyme sloppiness
Overlooked organic chemistry
All biological compounds are subjected to the same organic chemistry
2010
~354,000 flowering plant species
~7,000 cultivated for food consumption ~30 species supply >95 of food and energy needs ~20,000 used as medicine ~120 chemicals from plants as pharmaceuticals ~ 25% all pharmaceuticals come from plants, aspirin, morphine, artemisinin ~~10 plant species investigated for chemical constituents
Enzymes & Metabolism Lect No. Day
Subject
1 2
Sept 6 T
3 4 5
Reference Reading Voet/Voet/Pratt
Course introduction Concepts & design of metabolism
1,2 14
7 W
Enzymes: properties & classes Enzymes catalysis
11
8 Th
Enzymes: kinetics, regulation, & inhibition
12
6 7 8
9 F
Glycogen metabolism & gluconeogenesis Carbohydrates & Glucose metabolism citric acid cycle
16 8,15 17
9 Oct24 M 10
Energy production: oxidative phosphorylation Photosynthesis: light reactions, photophosphorylation
18 19
11 12
25 T
Photosynthesis: dark reactions Membrane properties & functions
19 9,10
13 14
26 W
Lipid metabolism Protein & amino acid metabolism
15 16
27 Th
Integration of metabolism; signal transduction
17 18 19 20
28
Class presentation & discussion Metabolite-protein interactions Circadian and effects on metabolism Autophagy and nutrient recycling Microbiome & metabolism; Genome editing ABC transporters and metabolite transport
29 S
F
20 17,22 13
Cell. 2014, 156:84-96. doi: 10.1016/j.cell.2013.12.016. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. De Vadder F1, Kovatcheva-Datchary P2, Goncalves D1, Vinera J1, Zitoun C1, Duchampt A1, Bäckhed F3, Mithieux G4.
Abstract Soluble dietary fibers promote metabolic benefits on body weight and glucose control, but underlying mechanisms are poorly understood. Recent evidence indicates that intestinal gluconeogenesis (IGN) has beneficial effects on glucose and energy homeostasis. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate, which are generated by fermentation of soluble fiber by the gut microbiota, activate IGN via complementary mechanisms. Butyrate activates IGN gene expression through a cAMP-dependent mechanism, while propionate, itself a substrate of IGN, activates IGN gene expression via a gut-brain neural circuit involving the fatty acid receptor FFAR3. The metabolic benefits on body weight and glucose control induced by SCFAs or dietary fiber in normal mice are absent in mice deficient for IGN, despite similar modifications in gut microbiota composition. Thus, the regulation of IGN is necessary for the metabolic benefits associated with SCFAs and soluble fiber. . Comment in You are what you eat. Nat Biotechnol. 2014 32(3):243-5. Gut microbiota: microbial metabolites feed into the gut-brain-gut circuit during host metabolism. [Nat Rev Gastroenterol Hepatol. 2014]
Class participation and presentation Problems Total points
60 pts 40 pts 100
Grading: The final letter grade will be based on the percentage of points earned in the three exams and term-paper. Grading Scale*: A 90-100% (Tentative) B 76-89% C 65-75% D 55-64% F <55% *The scale may be adjusted according to the overall distribution of the percentages gained by the class.
biochem201601@126.com; PW: biochem2016 For lecture PPT and problem sets biochem201602@126.com; PW: For turn in home work
What is Biochemistry? Biochemistry is the study of the chemistry of life processes, the study of structures, properties, metabolism, & functions of compounds found in living organisms, e.g. proteins, carbohydrates, lipids, nucleic acids, etc.
To study the biochemical processes by which biomolecules (e.g. proteins, carbohydrates, lipids, & nucleotides) are:
•
synthesized from what
•
degraded to what and for what
•
how some of the key processes are regulated
•
what are the functions for the molecules in: overall metabolism & networks
cellular regulation physiological processes: e.g. growth/development/disease significance in nutrition, health, agriculture, industry
Biochemistry is Multidisciplinary â&#x20AC;˘ Various disciplines contribute to understanding biochemistry:
Physics
Genetics
Chemistry
Physiology
Cell biology
Evolution
Lives come with diverse forms, but organisms are remarkably uniform at the molecular level
The diverse living organisms can be divided into three domains 1. Eukarya (Eukaryotes) 2. Bacteria (Eubacteria) 3. Archaea (Archaebacteria)
Biochemical Unity Underlies Biological Diversity
Mass composition data for the human body
Many Important Biomolecules are Polymers • Biopolymers - macromolecules created by joining many smaller organic molecules (monomers) • Condensation reactions join monomers (H2O is removed in the process) • Residue - each monomer in a chain
A Quick Overview 1. Laws of Thermodynamics
2. Properties of Water 3. Molecular Interaction of Biomolecules
The laws of thermodynamics What is the 1st Law? Energy is conserved.
i.e. it can neither be created or destroyed. The total energy of a system and surroundings is constant
Q? If the First Law of Thermodynamics is true, how can biological processes be carried out? Although energy cannot be created or destroyed, it can take on different forms, such as heat or chemical energy. Thus, the energy can be stored as chemical bond energy, which can be used to do work.
Energy Flow
3. The laws of thermodynamics
Entropy tends to increase.
What is the 2nd Law?
Entropy= a measure of the level of randomness or disorder in a system
O2
H2
Q? How can a cell exist if the Second Law of Thermodynamics is true?
A: Entropy in a local area can be decreased, but only at the expense of increased entropy in the larger area, or universe.
H2
O2
H2O
In the water formation process, the entropy of the system is reduced, but the entropy of the universe is increase due to the release of heat to the surroundings
The systemâ&#x20AC;&#x2122;s entropy (S) change alone cannot predict the spontaneity of a reaction/process.
G (Gibbs free energy) = Hsystem- TSsystem
G = free energy = the component of the total energy of a system that can do work H = enthalpy = heat content of a system T = absolute temp. in kelvin (K), constant in biological system
DG = DH - TDS • Free energy change (DG) can predict the equilibrium concentrations and direction of a reaction: DH = enthalpy change DS = entropy change T = absolute temp. in kelvin (K) • When DG<0, the reaction will proceed spontaneously in the direction written, exergonic • When DG>0, the reaction requires energy to proceed, endergonic For a reaction to be spontaneous, the free energy change must be negative, i.e. - ΔG
enthalpy change
entropy change
Properties of Water
4 Properties of Water 1)
Water is a polar molecule
2)
Water is an excellent solvent for polar molecules
3)
Water molecules interact with one another via hydrogen bond (ice structure)
4)
Water dramatically affects the interaction between molecules in aqueous solution
5)
Water weakens the strength of electrostatic attraction
Water affects the bonding abilities of biomolecules
5. Molecular Interaction of Biomolecules 1) 2) 3) 4) 5)
Covalent bond Electrostatic interactions Hydrogen bonds van der Waals forces Hydrophobic effect/interaction
They differ in geometry, strength, and specificity.
They differ in geometry, strength, and specificity. 1) Covalent bonds 2) Electrostatic interactions
1.5Ă&#x2026; in distance (C-C) 3 Ă&#x2026; in distance
85.4 kcal/mol in energy 1.4 kcal/mol in energy
between positively & negative charged atoms 3) Hydrogen bonds
2.4-3.5Ă&#x2026; in distance
1-3 kcal/mol in energy
between the partial positive charge of H & the partial negative charge of O, N
4) van der Waals forces 0.5-1 kcal/mol in energy Electrostatic interaction among permanent or induced dipoles, and London dispersion forces
5) Hydrophobic effect Nonpolar molecules have a tendency to aggregate in water to minimize their contact with water.
Cal = calorie = 4.184 joule (J), heat, energy
3) Hydrogen bonds Between the partial positive charge of H & the partial negative charge of O, N
DNA
Protein
4) van der Waals forces
Electrostatic interaction among permanent or induced dipoles, and London dispersion forces
London dispersion force: attraction resulting from transient dipoles (Erratic motions of electron cause uneven distributions of electrical charges within the molecules at any given time )
5) Hydrophobic effect Nonpolar molecules have a tendency to aggregate in water to minimize their contact with water.
The aggregation maximize the entropy of the entire system
Protein folding Cell membrane
Which one is: Electrostatic interaction Hydrogen bonding
C
A
Covalent Interaction van der Waals force Hydrophobic effect
B
D