Biochemistry I: Physical Foundations & Amino Acids

Biochemie I - Einleitung

• Introductory lecture notes for Biochemistry I, covering physical foundations of life and amino acids
• The lectures PDFs can be found on MS Teams- BC WS2024, MS-Teams-Code: 6r43mq5

Course Literature

• Lehninger/Nelson/Cox, „Prinzipien der Biochemie“, Spektrum Akad. Verlag
• Stryer, L., „Biochemie“, Spektrum Akad. Verlag
• Voet, D. & Voet, J.G., „Biochemie“, VCH, Weinheim

Living Organisms and Thermodynamics

• Living organisms are systems with low entropy, far from equilibrium with their environment
• Isolated systems develop towards thermodynamic equilibrium as per the second law of thermodynamics; the total entropy in the universe constantly increases
• Living organisms maintain low entropy in a universe where every spontaneous process increases entropy
• Isolation leads to thermodynamic equilibrium
  • Living organisms never reach equilibrium with their environment

Characteristics of Living Organisms

• Molecules and ions in organisms differ in concentration compared to their surroundings
• Life maintains complex macromolecular structures with low entropy
• The composition of molecules within an organism remains relatively constant over time; however, the population of molecules changes constantly
• Molecules and molecular complexes are constantly being formed and broken down

Energy and Order

• Creating order requires energy
• Cellular respiration process
  • C6H12O6 + 6O2 ⇌ 6CO2 + 6H2O
  • ΔGʻ° = ~-2840 kJ/mol
• Cellular respiration produces considerable energy
• This reaction occurs spontaneously because free energy decreases and entropy increases
• Life uses this energy to reduce entropy by synthesizing macromolecules, organelles, and cells

Energy Coupling

• Reactions involved in catabolism and anabolism are crucial for biological molecules

Gibbs Free Energy

• ΔG = ΔH - TΔS
• Units of free energy and enthalpy are measured in J/mol
• Entropy units are measured in J/mol * K

Spontaneity Prediction

• Predicting Spontaneity With AG Table 12.1
  • ΔH is negative, AS is positive then AG is negative: Always Spontaneous
  • ΔH is positive, AS is positive then AG is positive or negative: Spontaneous At High T
  • ΔH is negative, AS is negative then AG is positive or negative: Spontaneous At Low T
  • ΔH is positive, AS is negative then AG is positive: Never Spontaneous
  • ΔH = TAS results in AG of 0: At Equilibrium

Free Energy in Coupled Reactions

• Free energy in coupled reactions is additive
• Cells capture energy from the breakdown of organic molecules or from light, converting it into useful forms like ATP and NADPH
• ATP and NADPH are used as universal energy currencies to drive anabolic reactions, maintaining a stationary state without equilibrium.

Cells

• Cells are the Basic Unit of Many Biochemical Processes
• Difference between eukaryotic and prokaryotic cells.

Molecular Organization

• Living organisms are composed of relatively few components arranged and ordered in various ways

Biomolecules

• Classes of important biomolecules:
  • Proteins/Amino acids
  • Nucleic acids: RNA, DNA, carriers of genetic information
  • Carbohydrates: Sugars, structural and energy-storage molecules
  • Lipids/Fats: Membranes, reserve substances

Protein Structure and Function

• Catalysis: biological macromolecules as catalysts are enzymes
  • Share characteristics of classical chemical catalysts
  • Do not affect equilibria, lowers the activation energy of reactions
  • Emerge unchanged from reactions
  • High specificity and selectivity
• Transport and Storage: Hämoglobin (O2), Transferrin (Fe), Ferritin (Fe-Storage in liver)
• Coordinated movement:
  • Proteins are a major component of muscle tissue
  • Chromosome migration during mitosis (part of the cytoskeleton)
• Mechanical Support Function:
  • Skin, bones, hair, nails: collagen, keratin
  • High tensile strength

Protein function

• Immune Defense: Recognition of foreign structures by antibodies, with high specificity/adaptability based on molecular structure
• Signal Generation and Transmission:
  • Receptor proteins like Rhodopsin (receptor for light in the retina)
  • Excitable by small molecules, e.g. Acetylcholine (nerve impulses)
• Control of Growth and Differentiation:
  • Control of gene expression through regulatory enzymes
  • Communication in multicellular organisms

Proteins and Amino Acids

• Proteins are constructed from amino acids
• Primary Protein Structure is a sequence of a chain of amino acids
  • Amino group: NH2
  • Acidic carboxyl: COOH
  • R group

Proteinogenic Amino Acids

• There are 20 different proteinogenic amino acids Amino acids have:

  • An amino group
  • A carboxyl group
  • A specific side chain that influences chemical properties

• All Amino Acids in Proteins are L-Stereoisomers

• Amino acids are the building blocks of proteins

• The amino acid without a chirality center needs to be identified

Amino Acid Abbreviations

• Three-Letter and One-Letter Codes for Proteinogenic Amino Acids
  • Alanine (Ala, A)
  • Arginine (Arg, R)
  • Asparagine (Asn, N)
  • Aspartic Acid (Asp, D)
  • Cysteine (Cys, C)
  • Glutamine (Gln, Q)
  • Glutamic Acid (Glu, E)
  • Glycine (Gly, G)
  • Histidine (His, H)
  • Isoleucine (Ile, I)
  • Leucine (Leu, L)
  • Lysine (Lys, K)
  • Methionine (Met, M)
  • Phenylalanine (Phe, F)
  • Proline (Pro, P)
  • Serine (Ser, S)
  • Threonine (Thr, T)
  • Tryptophan (Trp, W)
  • Tyrosine (Tyr, Y)
  • Valine (Val, V)
  • Asparagine or aspartic acid (Asx, B)
  • Glutamine or glutamic acid (Glx, Z)

Amino Acid Groupings

• Examples of uncharged side chains: Glycine (Gly, G) and Alanine (Ala, A)
• Further examples of uncharged side chains: Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I) and Methionine (Met, M)
• Examples of Aromatic Amino Acids: Phenylalanine (Phe, F), Tyrosine (Tyr, Y) and Tryptophan (Trp, W)
• Examples of Hydroxy-Amino Acids: Serine (Ser, S) and Threonine (Thr, T)
• Examples of Basic Amino Acids: Lysine (Lys, K), Arginine (Arg, R) and Histidine (His, H)
• Examples of Acidic and Amidated Amino Acids: Aspartate (Asp, D), Glutamate (Glu, E), Asparagine (Asn, N) and Glutamine (Gln, Q)
• Example of an amino acid with a secondary amine: Proline (Pro, P)
• Examples of Sulfur-containing Amino Acids: Cysteine (Cys, C) and Methionine
• Cysteine residues can form disulfide bridges

Amino Acid Variants

• Examples of rare amino acids include Selenocysteine and Pyrrolysine
• Examples of amino acids created after protein synthesis:
  • 4-Hydroxyproline (e.g., in collagen),
  • 5-Hydroxylysine (e.g., in collagen),
  • 6-N-Methyllysine (e.g., in myosin), and
  • γ-Carboxyglutamate (e.g., in prothrombin)
• Examples of reversible amino acid modifications:
  • Phosphoserine,
  • Phosphothreonine,
  • Phosphotyrosine,
  • 6-N-Acetyllysine,
  • Glutamate γ-methyl ester, and
  • ω-N-Methylarginine
  • Adenylyltyrosine