chapter 1 The foundations of biochemistry Flashcards
Biochemistry: What & Why:
Biochemistry describes in molecular terms the structures, mechanisms and chemical processes shared by all organisms. It provides organizing principles that underlie life in all of its diverse forms- we call this ‘the molecular logic of life’.
Biochemistry provides important insights that can be applied in medicine/industry/agriculture- the ultimate concern is with the wonder of life itself.
The Features of Living Organisms:
- High degree of chemical complexity and microscopic organization.
- Systems for extracting, transforming and using energy from the environment.
- Defined functions for each of their components and regulated interactions between them.
- Mechanisms for sensing and responding to alterations in their surroundings.
- Capacity for precise self- replication and self assembly.
- Capacity to change over time by gradual evolution.
Cellular Foundations
Cells- eukaryotic vs prokaryotic
Basic cell structures & molecular hierarchy
three domains of life
bacteria, eukarya, archer
size hierarchy
water, glucose, antibody, virus, bacteria, cancer cell, period, baseball
phospholipid, sugar(amino acid), nucleotide, ATP, NAD
All cells are bounded by a
plasma membrance; have cytosol containing metabolites, coenzymes, inorganic ion, and enzymes; and have a set of genes contained with a nucleoid (bacteria and archaea) or nucleus (eukaryotes)
bacteria vs. animal cel
both: cytoplasm, membrane, ribosome
nucleus: animal
Nuecleoid: bacteria
Nuclear membrane and membrane bound organelles: animal cell
Bacteria cell structure
The simplest form of life, usually without organelles. But, bacteria do compartmentalize their cytoplasm.
fact: about 800 time longer than the cell
nucleiod, pili, cell envelope, flagella, ribosomes
Eukaryotic Cells
Includes plants, animals, fungi, protozoans, yeasts and some algaes
Large cells (10-100 μm diameter) – 10x bigger than prokaryotes
Plasma membrane
Cytoplasm
Cytoskeleton
Internal membranes and compartments (organelles)
Organelles contain organized complexes of macromolecules that perform a certain biological function
Most enzymes are compartmentalized
Nucleus
-Largest organelle in eukaryotic cells
-Bound by double membrane
-Storage of genetic info
-Site of most DNA synthesis and repair
-RNA synthesis
-Nuclear pores for transport of -RNA and proteins
-Nucleolus – transcription of rRNA; ribosome biogenesis; processing of RNA
Endoplasmic Reticulum (ER)
Network of interconnected, closed,
-Extends from
-Two types
-Ribosomes (ribonucleoprotein particles) made up of
-Network of interconnected, closed, membrane-bounded vesicles
-Extends from nuclear envelope to plasma membrane
-Two types (morphologically and functionally):
smooth (SER, to make cellular products like hormones andlipids) and rough (RER—ribosomes attached on cytosolic side, for protein synthesis)
-Ribosomes (ribonucleoprotein particles) made up of RNA and proteins, not bounded by a membrane
Mitochondria
-Have double membrane (inner and outer, outer membrane is smooth, while inner membrane forms elaborate folds called cristae)
-Place where most oxidative energy production occurs = “powerhouse” of cell
-Perform cellular respiration; form ATP
-Urea and heme synthesis
-Contain own genome; circular mtDNA
structure to molecular hierarchy
supramolecular complexes->Macromolecules->monomeric units
chromatin->DNA->nucleotides
Plasma membrane->protein->amino acids
cell wall->cellulose->sugars
bacterial cytoplasm is full of
molecules
cell envelope, flagellum, outer membrane, inner membrane, ribosome, DNA (nuclei)
Molecular Weight or Mass
Biochemistry uses both Molecular Weight (Mr) or Molecular
Mass (m) in “Daltons”
Carbon has Mr = 12 or m = 12D
Very Small Proteins have a mass of 10,000D = 10kD
Very Large ones have mass of >1million D = 1,000kD
(Titin a muscle protein ~3 million D)
kD= 3zeros
lipids monomer, polymer, supramolecular structure
monomer: fatty acid
Polymer: phospholipid
Supramolecular structure: membrane
proteins monomer, polymer, supramolecular structure
monomer: amino acid
Polymer: protein subunit
Supramolecular structure: protein complex
carbo monomer, polymer, supramolecular structure
monomer: glucose
Polymer: cellulose
Supramolecular structure: cell wall
nucleic acid monomer, polymer, supramolecular structure
monomer: nucleotide
Polymer: DNA
Supramolecular structure: chromosome
Biological Monomers
What to Look For = What’s Important:
What to Look For = What’s Important:
Functional Groups: amino, carboxyl, carbonyls (both), alcohol, methyl, phosphate, sulfhydryl, and others.
Covalent Bonds – single, double, triple.
Ionization state, or not.
Solubility
How Monomers are Polymerized
Weak Bonds = H-bonds, Ionic bonds, hydrophobic interactions, van der Waals forces.
Key points for cellular foundations:
-Cells:
-Bacterial & archaeal cells contain
-Cytoskeletal proteins assemble into
-There are many supramolecular complexes held together by
Cells: a plasma membrane; a cytosol (metabolites, coenzymes; inorganic ions; nucleoid (bacteria & archaea) or nucleus (eukaryotes).
Bacterial & archaeal cells contain cytosol, a nucleoid, and plasmids, all in a cell envelop. Eukaryotic cells have nucleus and specific organelles; organelles can be separated andstudies in isolation.
Cytoskeletal proteins assemble into long filaments that give cells shape and rigidity, facilitate cellular organells move in the cell.
There are many supramolecular complexes held together by noncovalent interaction, as part of a hierarchy of strutures.
Biochemistry is all about the
Most four abundant elements
Bulk elements for most biological polymers and major inorganic, physiological salts. We will add in the trace elements mainly as enzyme cofactors.
CHON
It is not important to know individual bond strengths, but rather to know ranges.
Single bonds are rotatable, double bonds
It is not important to know individual bond strengths, but rather to know ranges. Single bonds are 200 to 450 kJ/mole, double bonds are 500-700 kJ/mole and triple bonds are ~900 kJ/mole (hardest to make or break).
Single bonds are rotatable, double bonds not so.
Single bonds are rotatable, double bonds
Single bonds are rotatable, double bonds are not
Polar Covalent Bonds
The absolute value of the difference in electronegativity of two bonded atoms gives a rough measure of the polarity of the bond.
-When this difference is small (less than 0.5), the bond is nonpolar.
-When this difference is large (greater than 0.5), the bond is considered polar.
-If the difference exceeds approximately 1.8, sharing of electrons is no longer possible and the bond becomes ionic.
Bonds that hold things together
-Covalent
-Ionic interactions (weak or strong?)
-Hydrogen bonds
-Hydrophobic/hydrophilic interactions
-van der Walls interactions
bond energy of Van Der Waals
(dipole-dipole, London)
0.1 to 10 kJ/mol
bond energy of Hydrogen bonding
10 to 40 kJ/mol
Ionic energy
100-1000kJ/mol
Covalent energy
100 to 1000 kJ/mol
Stereoisomer
molecules with the same chemical bonds but differing spatial arrangement
cis/transisomerism(geometric isomerism)
s a form ofstereoisomerismdescribing therelative orientation offunctional groupswithin a molecule.
Chirality-
enantiomers
In chemistry, chirality usually refers to molecules.
Two mirror images of a chiral molecule are calledenantiomersoroptical isomers. Pairs of enantiomers are often designated as “right-“ and “left-handed”.
Naming conventions-
By configuration
By optical activity
By configuration, configuration standard Glyceraldehyde
By configuration:R- andS-
By optical activity: (+)- and (−)-
By configuration:D- andL- (configurational standard Glyceraldehyde)
thesis established optical rotation of compounds having the same empirical chemistry other than crystal shape and optical properties.
Pasteur’s Doctoral
Interactions between biomolecules are
specific
Stereoisomers Have Different
Biological effects
This is why colas sweetened with aspartame have a limited shelf life.
Living Organisms Exist in a
Dynamic Steady State, Never at Equilibrium with Their Surroundings
Pathways of metabolism
dynamic steady-state
Organisms Transform Energy and Matter from Their Surroundings
Two ways for energy:
Two ways for energy:
1) Absorb energy from sunlight (photosynthetic organisms (autotrophs)
2) Take up chemical fuel (e.g. glucose) and extract energy by oxidization (chemotrophs or heterotrophs)
Organisms Transform Energy and Matter from Their Surroundings
The biochemical process for energy in living cells contains multiple-step reactions:
C6H12O6 +6O2-> 6CO2 +6H2O +energy
ATP(Adenosine triphosphate ), ADP and AMP
ATP provides what
Adenosine triphosphate (ATP) provides energy. Here, each represents a phosphoryl group. The removal of the terminal phosphoryl group (shaded light red) of ATP, by breakage of a phosphoanhydride bond to generate adenosine diphosphate (ADP) and inorganic phosphate ion ( ), is highly exergonic, and this reaction is coupled to many endergonic reactions in the cell. ATP also provides energy for many cellular processes by undergoing cleavage that releases the two terminal phosphates as inorganic pyrophosphate ( ), often abbreviated PPi.
Basic thermodynamics
G
H
S
change ofG=change of
change of G=G
Reactants=
change of G*=
free energy is related to the
Keq=
change of G>0=
change of G=0=
change of G<0
endothermic/exothermic does not equal to
G-free energy
H-enthalpy
S-Entropy
change ofG=change ofH-t(change of S)
change of G=Gproducts-Greactnats
Reactants=substrates
change of G*=standard free energy change
free energy is related to the equilibrium Constant (Keq)
Keq=products over reactants
change of G>0= endergonic
change of G=0=equilibrium
change of G<0exergonic
Note: endothermic/exothermic does not equal to endergonic/exergonic
∆G +
∆G -
∆G 0
unfavorable
favorable-goes forward, to the right
equilibrium
exothermic
endothermic
exergonic
endergonic
release of heat
absorption of heat
exergonic-release of energy
endergonic-use of energy
∆S increase ∆H?
∆H increases ∆G?
∆H decreases, nonproprtional
∆G increases, directly proptional
How to speed reactions up
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
Universally used by living organisms (e.g. Enzymes)
Series of related enzymatically catalyzed reactions forms a pathway
Metabolic Pathway
Signal Transduction Pathway
Enzymes’ roles in Pathways
Metabolic Pathway
-produces energy or valuable materials
Signal Transduction Pathway
-transmits information
Enzymes’ roles in Pathways
-Enhance reaction rates (high selection; not being used up; no change for Keq)
-Decrease activation energy
Pathways are controlled in order to regulate levels of metabolites
Example of a negative regulation:
Product of enzyme 5 inhibits enzyme 1
phototrophs and chemotrophs
phototrophs-energy from light
–autorophs-carbon from CO2-example: cyanobacteria, vascular plants
–heterotrophs-carbon from organic compounds- example:purple bacteria, greed bacteria
Chemotrophs-energy from oxidation of chemical fuels (reduced fuel->oxidized fuel)
–lithographs- inorganic fuels-example: sulfur bacteria, hydrogen bacteria
–organotrophs-organic fuels-example: most bacteria all nonphotorophic eukaryotes
The single DNA molecule of E. coli, leaking out of a disrupted cell, is
hundreds of times longer than the cell itself and contains all the encoded information necessary to specify the cell’s structure and functions. The DNA contains about 4.6 million nucleotides, weighs less then 10-10 g, and has undergone only relatively minor changes during the past several million years. Right: Chromosome
The Structure of DNA Allows for its
AT bonds
CG bonds
Replication and Repair with Near-Perfect Fidelity
Complementarity of two strands of DNA. DNA is a linear polymer of covalently joined 4 deoxyribonucleotides: deoxyadenylate (A), deoxyguanylate (G), deoxycytidylate (C), and deoxythymidylate (T). Each nucleotide can associate very specifically but noncovalently with one other nucleotide in the complementary chain: A with T, and G with C. The two strands, held together by H bonds to form the DNA double helix. In DNA replication, the two strands (blue) separate and two new strands (pink) are synthesized.
AT-2 h bonds
C-G- 3 h bonds
Central Dogma
DNA code ->Transcription -> Translation -> Protein
Central Dogma extended:
: DNA -> RNA-> Unfolded Protein-> Folded Protein
Changes in the Hereditary Instructions Allow
evolution
FIGURE 1–33 Gene duplication and mutation: one path to generate new enzymatic activities. In this example, the single hexokinase gene in a hypothetical organism might occasionally, by accident, be copied twice during DNA replication, such that the organism has two full copies of the gene, one of which is superfluous. Over many generations, as the DNA with two hexokinase genes is repeatedly duplicated, rare mistakes occur, leading to changes in the nucleotide sequence of the superfluous gene and thus of the protein that it encodes. In a few very rare cases, the altered protein produced from this mutant gene can bind a new substrate—galactose in our hypothetical case. The cell containing the mutant gene has acquired a new capability (metabolism of galactose), which may allow it to survive in an ecological niche that provides galactose but not glucose. If no gene duplication precedes mutation, the original function of the gene product is lost.
Homolog, Ortholog, Paralog
Homology is the blanket term, both ortho- and paralogs are homologs.
Orthologs are homologous genes that are the result of aspeciation event. same function
Paralogs are homologous genes that are the result of aduplication event. different function
orthologs are genes that are related by vertical descent from a common ancestor and encode proteins with the same function in different species. By contrast, paralogs are homologous genes that have evolved by duplication and code for protein with similar, but not identical functions.”
____can be edited nowadays
Genomic DNA with CRISPR
Evolution of Eukaryotes through
Enosymbiosis
The earliest eukaryote, an anaerobe, acquired endosymbiotic purple bacteria, which carried with them their capacity for aerobic catabolism and became, over time, mitochondria. When photosynthetic cyanobacteria
subsequently became endosymbionts of some aerobic eukaryotes, these cells became the photosynthetic precursors of modern green algae and
plants.
Key points for physical foundations:
-Living cells are
-ATP and its importance
-The tendency for a chemical reaction to proceed toward equilibrium can be expresses by
ΔG < 0, the reaction is
-The standard free-energy change, ΔG° is dependent on the
Enzymes are
-Living cells are open systems, exchanging matter and energy with their surroundings, maintain themselves in a dynamic steady state distant from equilibrium.
-ATP and its importance in energy transfer.
-The tendency for a chemical reaction to proceed toward equilibrium can be expresses by ΔG, and ΔG = ΔH - TΔS.
ΔG < 0, the reaction is exergonic and tends to go toward completion; ΔG > 0, it is endergonic and tends to in the reverse direction.
-The standard free-energy change, ΔG° is dependent on the equilibrium constant, Keq, ΔG° = -RTln Keq.
-Enzymes are biocatalysts, can increase the reaction rate by many orders of magnitudes, but the catalytic activity is enzymes in cells is regulated.
Key points for chemical foundations:
-Carbon bonding versatility, a variety of functional groups, can form different types
-Molecular configuration can be changed only by
For C with 4 different substituents (a chiral C), the substituents groups can be arranged in
Only one stereoisomer
-Molecular conformation is the
-Interactions between biological molecules are
-Carbon bonding versatility, a variety of functional groups, can form different types of biomolecules.
-Molecular configuration can be changed only by breaking covalent bonds. For C with 4 different substituents (a chiral C), the substituents groups can be arranged in two different ways, generating stereoisomers with distinct properties. Only one stereoisomer is bologically active.
-Molecular conformation is the position of atoms in space that can be changed by rotation about single bond, without breaking covalent bonds.
-Interactions between biological molecules are almost invariable stereospecific.
Key points for cellular foundations:
-Cells: a plasma membrane; a cytosol (metabolites, coenzymes; inorganic ions; nucleoid (bacteria & archaea) or nucleus (eukaryotes).
-Bacterial & archaeal cells contain cytosol, a nucleoid, and plasmids, all in a cell envelop. Eukaryotic cells have nucleus and specific organelles; organelles can be separated andstudies in isolation.
-Cytoskeletal proteins assemble into long filaments that give cells shape and rigidity, facilitate cellular organells move in the cell.
-There are many supramolecular complexes held together by noncovalent interaction, as part of a hierarchy of strutures.
