Comprehensive Study Guide: Foundations of Biochemistry (BIOCH 200)

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Introduction to Biochemistry

Biomolecules

Biochemistry focuses on the chemical processes within and related to living organisms. Understanding the structure and function of biomolecules is foundational to the field.

Trace elements: Essential elements required in minute quantities for biological processes (e.g., Fe, Zn, Cu).
Amino acids: Organic compounds containing both amino (-NH2) and carboxyl (-COOH) groups; building blocks of proteins.
Carbohydrates: Organic molecules composed of carbon, hydrogen, and oxygen; serve as energy sources and structural components.
Monosaccharide: The simplest form of carbohydrate (e.g., glucose, fructose).
Nucleotide: Monomeric units of nucleic acids, consisting of a nitrogenous base, a sugar, and phosphate group(s).
Lipid: Hydrophobic or amphipathic molecules, including fats, oils, and steroids.
Monomer: A single molecular unit that can join with others to form a polymer.
Polymer: Large molecules composed of repeating monomer units (e.g., proteins, nucleic acids, polysaccharides).
Residue: A single monomer unit within a polymer chain.
Peptide bond: Covalent bond linking amino acids in proteins.
Phosphodiester bond: Covalent bond joining nucleotides in nucleic acids.
Glycosidic bond: Covalent bond joining monosaccharides in carbohydrates.

Most abundant elements in biological molecules: Carbon (C), Hydrogen (H), Oxygen (O), Nitrogen (N), Phosphorus (P), Sulfur (S).

Major classes of biological molecules: Proteins, nucleic acids, carbohydrates, lipids.

Major functions of biological polymers:

Proteins: Catalysis (enzymes), structure, transport, signaling.
Nucleic acids: Information storage and transfer (DNA, RNA).
Carbohydrates: Energy storage, structure, recognition.
Lipids: Energy storage, membrane structure, signaling.

Water and Its Properties

Key Terms and Interactions

Polarity: Distribution of electrical charge leading to partial positive and negative regions.
Hydrogen bond: Weak interaction between a hydrogen atom covalently bonded to an electronegative atom and another electronegative atom.
Electrostatic interaction: Attraction or repulsion between charged particles.
Van der Waals radius: The effective size of an atom for non-covalent interactions.
Electronegativity: Atom's tendency to attract electrons in a bond.
Van der Waals interaction: Weak, non-covalent interactions due to transient dipoles.
Dipole-dipole interaction: Attraction between polar molecules.
London dispersion forces: Weakest intermolecular forces due to temporary dipoles.
Hydrophilic: Water-attracting (polar) molecules.
Hydrophobic: Water-repelling (nonpolar) molecules.
Hydrophobic effect: Tendency of nonpolar substances to aggregate in aqueous solution, driven by entropy.
Amphiphilic/Amphipathic: Molecules with both hydrophilic and hydrophobic regions (e.g., phospholipids).
Micelle: Spherical aggregate of amphipathic molecules in water.

Major types of electrostatic forces: Ionic interactions, hydrogen bonds, van der Waals interactions.

Relative strengths of bonds: Covalent > Ionic > Hydrogen bond > van der Waals.

Hydrophobic effect and entropy: Aggregation of hydrophobic molecules increases the entropy of water, making the process thermodynamically favorable.

Identifying hydrophobic/hydrophilic molecules: Polar groups (e.g., -OH, -NH2) indicate hydrophilicity; hydrocarbon chains indicate hydrophobicity; amphipathic molecules contain both.

Nucleotides and Nucleic Acids

Nucleotides

Purine bases: Adenine (A), Guanine (G); double-ring structures.
Pyrimidine bases: Cytosine (C), Thymine (T), Uracil (U); single-ring structures.
Sugars in nucleotides: Ribose (RNA), 2'-deoxyribose (DNA).
Nucleoside: Base + sugar; Nucleotide: Base + sugar + phosphate.
Deoxynucleoside: Nucleoside with deoxyribose sugar.
Major bases: Adenine, Guanine, Cytosine, Thymine (DNA), Uracil (RNA).
Hydrogen bonding: Purines and pyrimidines form specific hydrogen bonds (A-T/U: 2 bonds; G-C: 3 bonds).

Primary Structure of Nucleic Acids

Nucleic acid: Polymer of nucleotides (DNA or RNA).
RNA vs. B-DNA: RNA is usually single-stranded; B-DNA is the common double-helical form of DNA.
Bonds: Ester, phosphoester, and phosphodiester bonds link nucleotides.
Directionality: Nucleic acids have 5' (phosphate) and 3' (hydroxyl) ends; sequences are written 5' to 3'.
RNA susceptibility: RNA is more prone to alkaline hydrolysis due to the 2'-OH group.
Base stacking: Stabilized by van der Waals forces and hydrophobic interactions.

Secondary Structure of Nucleic Acids

Mononucleotide, dinucleotide, oligonucleotide: Molecules with one, two, or a few nucleotide units, respectively.
Chargaff’s rules: In DNA, %A = %T and %G = %C.
Antiparallel: DNA strands run in opposite directions (5' to 3' and 3' to 5').
B-DNA double helix: Two antiparallel strands, right-handed helix, stabilized by hydrogen bonds and base stacking.
Grooves: Major and minor grooves allow protein binding and recognition.
RNA vs. DNA 3D structure: RNA can form complex secondary/tertiary structures; DNA is typically a double helix.

Denaturation of Nucleic Acids

Denaturation: Separation of double-stranded DNA into single strands by heat, pH, or chemicals.
Melting: The process of DNA denaturation; Tm: Temperature at which half the DNA is denatured.
Hypochromic effect: Double-stranded DNA absorbs less UV light than single-stranded (hyperchromic effect upon melting).
Renaturation/annealing: Reformation of double-stranded DNA from single strands.
Tm and GC content: Higher GC content increases Tm due to more hydrogen bonds.
Effect of pH and ionic strength: Extreme pH or low ionic strength destabilizes DNA.
RNA melting: RNA can denature, but its structure is more variable.

Protein Structure and Function

Amino Acids and Their Properties

Generic structure: Central (α) carbon, amino group, carboxyl group, hydrogen, and variable side chain (R group).
20 amino acids: Each with unique side chains; classified as nonpolar, polar, or charged.
Charge states: At physiological pH (~7), amino acids are zwitterions (both + and - charges).
Chirality: All except glycine are chiral (asymmetric α-carbon).
Special side chains: Ser, Thr, Tyr (can be phosphorylated); Cys (forms disulfide bonds); His (buffering); Gly (flexibility); Pro (rigid structure).

Peptide Bonds and Protein Primary Structure

Primary structure: Linear sequence of amino acids in a polypeptide.
Residues: Amino acids within a polypeptide chain.
Peptide bond: Planar and rigid due to partial double-bond character.
Polypeptide backbone: Repeating N-Cα-C units.

Secondary Structure of Polypeptides

Levels of structure: Primary, secondary (α-helix, β-sheet), tertiary, quaternary.
α-helix: Right-handed coil stabilized by hydrogen bonds.
β-sheet: Parallel or antiparallel strands stabilized by hydrogen bonds.
Regular vs. irregular structure: Regular (α-helix, β-sheet); irregular (loops, turns).
Stabilization: Mainly by hydrogen bonds.

Tertiary and Quaternary Structure

Tertiary structure: 3D folding of a single polypeptide.
Quaternary structure: Association of multiple polypeptide chains.
Surface vs. core: Hydrophobic residues in core; polar/charged on surface.
Stabilization: Hydrophobic interactions, hydrogen bonds, ionic interactions (salt bridges), disulfide bonds.
Prosthetic group: Non-protein component required for function (e.g., heme).
Apoprotein: Protein without prosthetic group; Holoprotein: Protein with prosthetic group.

Myoglobin and Hemoglobin

Structures: Myoglobin (monomer), hemoglobin (tetramer).
Functions: Myoglobin stores O2 in muscle; hemoglobin transports O2 in blood.
Oxygen binding curves: Myoglobin (hyperbolic), hemoglobin (sigmoidal, cooperative binding).
Histidine roles: Proximal and distal histidines stabilize O2 binding.
Allosteric effectors: Molecules that modulate protein activity (e.g., BPG, H+ for hemoglobin).
Bohr effect: Lower pH (higher H+) stabilizes T state, promoting O2 release.
Fetal vs. adult hemoglobin: Fetal hemoglobin has higher O2 affinity due to structural differences.

Enzymes

What are Enzymes?

Enzyme: Biological catalyst, usually a protein, that accelerates reactions without being consumed.
Specificity: Enzymes act on specific substrates.
Substrate: Molecule upon which an enzyme acts.
Regulation: Enzyme activity can be modulated by various mechanisms.

How Do Enzymes Work?

Free energy diagrams: Show energy changes during reactions; enzymes lower activation energy ().
Spontaneity: A reaction is spontaneous if .
Mechanisms of catalysis: Proximity/orientation, transition state stabilization, acid-base catalysis, covalent catalysis.
Active site: Region where substrate binds and reaction occurs.
Induced fit: Enzyme changes shape upon substrate binding.
Cofactor, cosubstrate, prosthetic group: Non-protein components required for activity.

Regulating Enzyme Activity

Regulation mechanisms: Allosteric regulation, covalent modification (e.g., phosphorylation), proteolytic activation, gene expression, compartmentalization, substrate availability.
Competitive inhibition: Inhibitor competes with substrate for active site; can be overcome by increasing substrate concentration.
Allosteric regulation: Effectors bind at sites other than the active site, altering enzyme activity.
Protein phosphorylation: Addition/removal of phosphate groups by kinases/phosphatases modulates activity.

Biological Membranes

Fatty Acids, Triacylglycerols, and Membrane Lipids

Lipid classification: Based on hydrophobicity/amphipathic nature.
Types of lipids: Fatty acids, triacylglycerols (TAGs), phospholipids, sterols (e.g., cholesterol).
Fatty acid structure: Long hydrocarbon chain with terminal carboxyl group; α and β carbons are adjacent to the carboxyl group.
Amphipathic: Fatty acids have hydrophobic tails and hydrophilic heads.
Saturated vs. unsaturated: Saturated (no double bonds), monounsaturated (one double bond), polyunsaturated (multiple double bonds).
Cis/trans double bonds: Cis bends the chain; trans is straighter.
Melting point: Increases with chain length, decreases with unsaturation.
Triacylglycerol vs. glycerophospholipid: TAGs are storage fats; phospholipids are membrane components.
Cholesterol: Modulates membrane fluidity; fits between phospholipids in bilayer.

Structure of Biological Membranes

Lipid bilayer: Fluid, dynamic structure; dimensions vary with composition.
Cholesterol: Increases membrane stability and modulates fluidity.
Membrane proteins: Integral, peripheral, and lipid-anchored; integral proteins span the bilayer.
Protein structures in membranes: α-helices and β-barrels.

Transport Across Membranes

Passive transport: No energy required; includes simple diffusion and facilitated diffusion.
Active transport: Requires energy (e.g., ATP hydrolysis).
Transporters vs. channels: Transporters bind and move substances; channels form pores.
Uniport, symport, antiport: Uniport moves one substance; symport moves two in same direction; antiport moves two in opposite directions.
Na+/K+ ATPase: Pumps Na+ out and K+ in, using ATP.
Glucose transport: Involves both active and facilitated transport mechanisms.

Introduction to Metabolism

Purposes and Concepts

Major purposes: Energy production and biosynthesis.
Catabolic vs. anabolic pathways: Catabolic break down molecules (release energy); anabolic build molecules (require energy).
Amphibolic: Pathways that function in both catabolism and anabolism (e.g., citric acid cycle).
Anapleurotic: Reactions that replenish intermediates of metabolic cycles.

Essential Concepts in Metabolism

Free energy change (): Determines reaction direction; negative is spontaneous.
Standard free energy () and biochemical standard (): Reference values for comparing reactions.
Electron carriers: NAD+, NADP+, FAD; shuttle electrons in redox reactions.
High-energy intermediates: ATP, GTP, phosphocreatine; store and transfer energy.
ATP hydrolysis: Releases large, negative free energy; drives endergonic processes.
Coupled reactions: Energetically unfavorable reactions are driven by coupling to favorable ones (e.g., glucose phosphorylation).
Phosphocreatine: Serves as a rapid ATP buffer in muscle.
Regulation: Rate-limiting steps, reciprocal regulation, product and feedback inhibition.

Nucleotides as High-Energy Molecules and Electron Carriers

Phosphoanhydride bond: High-energy bond in ATP and other nucleoside triphosphates.
Hydrolysis of phosphoanhydride bonds: Highly favorable due to relief of electrostatic repulsion and resonance stabilization.
NAD+, NADP+, FAD: Dinucleotides functioning as electron carriers.
Reduction equations:

Oxidative Phosphorylation

Location: Inner mitochondrial membrane.
Electron transport chain (ETC): Series of complexes that transfer electrons from NADH/FADH2 to O2, pumping protons to generate a gradient.
ATP synthase: Uses proton gradient to synthesize ATP; Fo (membrane channel), F1 (catalytic).
Terminal electron acceptor: O2; equation:
Uncouplers: Increase O2 consumption by dissipating the proton gradient.
Brown adipose tissue: Generates heat via uncoupling protein (thermogenin).
ATP yield: Fewer ATP per FADH2 than NADH due to entry points in ETC.

Glycolysis and Glucose Metabolism

Purpose: Breakdown of glucose to pyruvate, generating ATP and NADH.
Location: Cytoplasm.
Key steps: Three regulated steps catalyzed by hexokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase.
ATP yield: Gross: 4 ATP; Net: 2 ATP per glucose.
Regulation: Allosteric effectors, feedback inhibition, feed-forward activation.
High-energy intermediates: 1,3-bisphosphoglycerate, phosphoenolpyruvate.

Fates of Pyruvate

Aerobic fate: Conversion to acetyl-CoA (enters citric acid cycle).
Anaerobic fates: Conversion to lactate (muscle), ethanol (yeast).
Lactate: Dead-end in muscle; can be transported to liver for gluconeogenesis (Cori cycle).
Acidotic damage: Accumulation of H+ during anaerobic glycolysis.
Pyruvate dehydrogenase: Converts pyruvate to acetyl-CoA; tightly regulated by energy status and covalent modification.

The Citric Acid Cycle (CAC)

Location: Mitochondrial matrix.
Functions: Oxidizes acetyl-CoA to CO2, generates NADH, FADH2, GTP/ATP.
Regulation: By substrate availability, product inhibition, allosteric effectors.
Amphibolic: Functions in both catabolism and anabolism.
Anapleurotic reactions: Replenish CAC intermediates (e.g., pyruvate carboxylase forms oxaloacetate).

Table: Comparison of Major Biological Polymers

Polymer	Monomer	Bond Type	Main Functions
Protein	Amino acid	Peptide bond	Catalysis, structure, transport, signaling
Nucleic acid	Nucleotide	Phosphodiester bond	Information storage and transfer
Polysaccharide	Monosaccharide	Glycosidic bond	Energy storage, structure
Lipid (not always polymeric)	Fatty acid, glycerol, etc.	Ester bond (in TAGs, phospholipids)	Energy storage, membranes, signaling

Additional info: This guide expands on the syllabus learning objectives with academic context, definitions, and examples to serve as a comprehensive study resource for foundational biochemistry topics.