1. CHAPTER 1 Foundations of Biochemistry
Learning Objectives
Distinguishing features of living organisms
Structure and function of cells and organelles
Roles of small and large biomolecules
Energy transformation in living organisms
Regulation of metabolism and catalysis
Coding of genetic information in DNA
Mutation, selection and evolution
Molecular phylogeny

2. Fundamentals of Biochemistry
Chapter 1:
Fundamentals of Biochemistry

3. “life’s processes at the level of molecules”
What is Biochemistry?
In previous classes you have encountered aspects of this subject in Chemistry and Biology
In this course you will be introduced more complex but exciting concepts in Biochemistry
Biochemists use basic laws of
Chemistry, Biology and Physics to explain?
Processes of living cells
Even though the word Biochemistry has become common place in our language, a concise meaningful definition is difficult
Simplest definition is:
“The chemistry of the living cell”
Overall goal of biochemistry is to describe:
“life’s processes at the level of molecules”

4. All biological processes including
vision, digestion, thinking, motion, immunity and disease conditions result from the actions of molecules
Therefore, in order to describe these processes …? One must have a
Knowledge of chemical structures of participating molecules (Conformational study)
Understanding of the biological function of cellular molecules (Informational)
study of energy flow is living system ---- (Bioenergetics)

5. Brief History of Biochemistry
Physical Science
(Chemistry, Physics)
Biological Science

6. Biochemistry- Molecular Biology
The term molecular biology was first coined in 1938 by Rockefeller Foundation
Biochemistry and molecular biology have similar goals; however, their approaches to solving problems have been different in the past:
Molecular biologists– emphasize the study of genetic materials (RNA and DNA), especially its role in biological information transfer and they use more biological experimental approaches involving organisms, recombinant DNA and molecular genetics
Biochemists– focus on the structure and function of all biomolecules and energy relationships among them.
In fact, most scientists consider the fields to be the same.
Both becoming indistinguishable because they seek answers to the same question: what is life?

7. Cells: Universal Building Blocks
Living organisms are made of cells
Simplest living organisms are singe-celled
Larger organisms consists many cells with different functions
Not all the cells are the same

8. Three Domains of Life
Differences in cellular and molecular level define three distinct domains of life

9. Bacterial, Plant, and Animal Cells are Different
The internal structure and properties of cells from organisms in different kingdoms are rather different but fundamental macromolecules are highly conserved

10. Components of Bacterial Cell
Structure Composition Function
Cell wall Peptidoglycan Mechanical support
Cell membrane Lipid + protein Permeability barrier
Nucleoid DNA + protein Genetic information
Ribosomes RNA + protein Protein synthesis
Pili Protein Adhesion, conjugation
Flagella Protein Motility
Cytoplasm Aqueous solution Site of metabolism

11. Eukaryote Cells: More Complexity
Have nucleus by definition
protection for DNA; site of DNA metabolism
selective import and export via nuclear membrane pores
some cells become anuclear (red blood cells)
Have membrane-enclosed organelles
Mitochondria for energy in animals, plants and fungi
Chloroplasts for energy in plant
Lysosome for digestion of un-needed molecules
Spatial separation of energy-yielding and energy consuming reactions helps cells to maintain homeostasis and stay away from equilibrium

12. Components of Animal Cells

13. Chemical Composition of Cell

15. Cytoplasm and Cytoskeleton
Cytoplasm is highly viscous solution where many reactions take place
Cytoskeleton consists of microtubules, actin filaments, and intermediate filaments
cell shape
transport paths
movement

16. FIGURE 1–11 Structural hierarchy in the molecular organization of cells. The nucleus of this plant cell is an organelle containing several types of supramolecular complexes, including chromatin. Chromatin consists of two types of macromolecules, DNA and many different proteins, each made up of simple subunits.

17. Living Systems Extract Energy
From sunlight
plants
green bacteria
cyanobacteria
From fuels
animals
most bacteria
Energy input is needed in order to maintain complex structures and be in a dynamic steady state, away from the equilibrium

18. Energy and Carbon Sources
All organisms require energy and carbon for life
We can also classify based in the sources of energy and carbon

19. Today’s topics Elementals of life Biological molecules Thermodynamics
Biochemical Reactions
Chemical and Molecular Evolution

20. Elements of life Elements H, O, N, P, S are also common
Metal ions (e.g. K+, Na+, Ca++, Mg++, Zn++, Fe++) play important roles in metabolism
Together, about 30 elements are essential for life

21. Elemental composition of Life: Unique Role of Carbon
Biomolecules are carbon-based

22. Biological Molecules Typically Have Several Functional Groups

24. Structure of Biological Molecules is Important
The function of molecules strongly depend on three-dimensional structure

25. Stereoisomers have Different Biological Properties
Cis and trans isomers have also different physical and chemical properties

26. Optical Isomers have Different Biological Properties
Enantiomers have identical physical properties (except regard to polarized light) and react identically with achiral reagents.
Diastereomers have different physical and chemical
D and L Are Outmoded and Wrong
Students who take biochemistry are exposed to an old, confusing, and often incorrect method of specifying configurations at chiral centers as D or L. This scheme was devised by Emil Fischer, a German organic chemist who worked extensively with carbohydrates. Here's how it is supposed to work.The compound glyceraldehyde, HOCH2CH(OH)CHO, was chosen as the standard for defining configuration.
The enantiomer that rotates plane polarized light clockwise (+) was arbitrarily labeled D
The other enantiomer (-) became L.
As shown, the assignments in modern notation are R and S, respectively. (Note: it will not always work out that D = R and L=S; this is an accident here.)
The source of the D and L labels was the Latin words dexter (on the right) and laevus (on the left)
R comes from rectus (right-handed) and S from sinister (left-handed)
Any other molecule containing a single chiral center was to be assigned as D or L by imagining a resemblance between the ligands on its chiral center and those in glyceraldehyde
The enantiomer having the "same or similar" groups in the same places as D-glyceraldehyde becomes D.
Thus, for example, the naturally occuring form of the amino acid cysteine was labeled L.
When more than one chiral center is present, similarity is defined only by the arrangement of ligands on the highest numbered chiral center, and the assignment of D or L is made on the basis of that center only.
The configuration at the other centers usually is specified by giving the diastereomeric molecules entirely different names.
The student is expected simply to memorize which arrangement of ligands goes with which names.
For example, look at the two aldotetroses below:
The D and L were assigned on the basis of the arrangement at the lower of the two chiral centers.
That the two sugars are diastereomers is specified by giving them different names.
Clearly, this system is impossible to apply widely, requires extensive memorizing of structures, and is also seriously ambiguous.
Consider for example, the reaction outline shown below. Here D-glyceraldehyde is converted into lactic acid by reactions that do not break any bonds to the chiral center! (These conversions actually have been carried out in the laboratory.)
Which structure is D-lactic acid?
For more examples of the inadequacy and ambiguity of this scheme, see an article in the Journal of Chemical Education,1971, 48, 597. Isn't it about time biochemistry moved into the 20th century?
R = rectus (right-handed)
S = sinister (left-handed)

27. Interactions between Biomolecules are Specific
Macromolecules have unique binding pockets
Only certain molecules fit in well and can bind
Binding of chiral biomolecules is stereospecific

28. Thermodynamics - Energetic Driving Forces
G = H – TS
Free Energy = Enthalpy – (T × Entropy)
Spontaneous Chemical Processes are characterized by reduction in Free Energy
Reactants => Products
GProducts – GReactants = ΔG = ΔH – TΔS
Spontaneous if ΔG is negative

29. Free Energy
Every Chemical Compound has a standard Free Energy of Formation G°
The standard state is typically 1 M, 25°C
For biochemical reactions pH (7.0) is specified as well
The conversion of 1 mole of:
A + B => C + D
ΔG° = (G°C + G°D ) - (G°A + G°B )

30. Chemical Equilibrium A + B <==> C + D ΔG = ΔG° + RT ln
At equilibrium forward and reverse reactions balance, ΔG = 0
ΔG° = - RT ln Keq

31. Unfavorable and Favorable Reactions
Synthesis of complex molecules and many other metabolic reactions requires energy (endergonic)
A reaction might be thermodynamically unfavorable (G° > 0)
Creating order requires work and energy
Breakdown of some metabolites releases significant amount of energy (exergonic)
Such metabolites (ATP, NADH, NADPH) can be synthesizes using the energy from sunlight and fuels
Their cellular concentration is far higher than their equilibrium concentration.

32. ATP: Chemical Currency of Energy

33. Energy Coupling
Chemical coupling of exergonic and endergonic reactions allows otherwise unfavorable reaction
The “high-energy” molecule (ATP) reacts directly with the metabolite that needs “activation”

34. Kinetics – Reaction Rate Acceleration
Higher temperatures
Stability of macromolecules is limiting
Higher concentration of reactants
Costly as more valuable starting material is needed
Change the reaction by coupling to a fast one
Universally used by living organisms
Lower activation barrier by catalysis

35. Catalysis
A catalyst is a compound that increases the rate of a chemical reaction
Catalysts lower the activation free energy G‡
Catalysts does not alter G°
Catalysis offers:
Acceleration under mild conditions
High specificity
Possibility for regulation

36. FIGURE 6-3 Reaction coordinate diagram comparing enzyme-catalyzed and uncatalyzed reactions. In the reaction S → P, the ES and EP intermediates occupy minima in the energy progress curve of the enzyme-catalyzed reaction. The terms ΔG‡uncat and ΔG‡cat correspond to the activation energy for the uncatalyzed reaction and the overall activation energy for the catalyzed reaction, respectively. The activation energy is lower when the enzyme catalyzes the reaction.

37. Energy Flows through ATP and redox carriers to couple Catabolic and Anabolic Pathways

38. Series of Related Reactions Forms a Pathway
Metabolic Pathway
produces energy or valuable materials
Signal Transduction Pathway
transmits information

39. Pathways Are Controlled in Order to Regulate Levels of Metabolites
Example of a negative regulation:
Product of enzyme 5 inhibits enzyme 1

40. The Central “Dogma” of Biochemistry
Pathway for the flow of genetic information:
DNA → RNA → Protein
DNA stores information
RNA transmits information
Protein function manifests
information

41. Genetic and Evolutionary Foundations
Life on Earth arose 3.5 – 3.8 billion years ago
Formation of self-replicating molecules a key step
DNA? – Info, Self Template
Proteins? – Function
RNA? – Both
Evolutionary Evidence is in DNA sequences TODAY!

42. RNA World?
RNA can acts both as the information carrier and biocatalyst
There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact.

43. Evolution of Eukaryotes through Endosymbiosis
FIGURE 1–36 Evolution of eukaryotes through endosymbiosis. The earliest eukaryote, an anaerobe, acquired endosymbiotic purple bacteria (yellow), which carried with them their capacity for aerobic catabolism and became, over time, mitochondria. When photosynthetic cyanobacteria (green) subsequently became endosymbionts of some aerobic eukaryotes, these cells became the photosynthetic precursors of modern green algae and plants.

44. Natural Selection Favors Some Mutations
DNA replication is amazingly, but not absolutely, error-free
Mutations occur more or less randomly
Most mutations are “silent”
Many are deleterious
Rare mutations that yield an advantage in a given environment are more likely to be propagated

45. Assignment Define the following terms
Vital force theory - Enantiomers
Gene and genetic code - Aquaporin
Recombinant DNA - Bioinformatics
Out of 100 plus chemical elements, only about 31 (28%) occur naturally in plants and animals, How these elements were selected?
Make a list of Nobel Laureates in Chemistry and Physiology from 2005 to 2013 and enlist their key findings relevant to Biochemistry
Note: prepare hand written assignment on assignment pages

46. Assignment What are advanced DNA sequencing techniques, make a list
Differentiate between Chemical Reactions and Biochemical Reactions
What are features of archeae bacteria?
What do you mean by mycoplasma?
Differentiate Chemical, Molecular and Biological Evolution
Note: prepare hand written assignment on assignment pages