BIO CHEM Midterm 1

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Why is water a polar molecule?

Because the O–H bonds are polar and the molecule is bent, giving an uneven charge distribution (oxygen end δ–, hydrogen end δ+).

Why is water an excellent solvent for polar and ionic substances?

Water’s polarity allows it to surround (hydrate) charged and polar molecules. It forms hydrogen bonds or dipole interactions with solutes, and its high dielectric constant shields and weakens electrostatic attractions, helping dissolve ionic compounds.

How many hydrogen bonds can one water molecule form?

Up to four hydrogen bonds (each water has two hydrogen atoms to donate and two lone pairs on oxygen to accept hydrogen bonds).

What is a hydrogen bond?

A weak electrostatic attraction between a hydrogen atom covalently bonded to an electronegative atom (like O or N) and another electronegative atom with a lone pair. For example, hydrogen bonds form between water molecules, or between N–H and C=O groups in protein backbones.

What are the major types of noncovalent interactions in biological systems?

Hydrogen bonds, ionic (electrostatic) interactions, dipole–dipole interactions (including hydrogen bonding as a special case), London dispersion (van der Waals) forces, and hydrophobic interactions.

What is the hydrophobic effect?

The tendency of nonpolar molecules or groups to aggregate in water to minimize disruption of water’s hydrogen-bonded network. Water molecules exclude hydrophobic groups, driving those groups together (e.g. oil droplets, protein folding, membrane formation).

What is pH?

The negative logarithm of the hydrogen ion concentration: pH = –log[H⁺].

What is the ion product of water (Kₙ) at 25 °C?

The ion product (Kw) is [H⁺][OH⁻] = 1.0 × 10⁻¹⁴ at 25 °C. This means in pure water, [H⁺] = 1×10⁻⁷ M (pH 7), and pH + pOH = 14 at 25 °C.

What is pKa?

The negative logarithm of the acid dissociation constant (Ka) of a weak acid. It is a measure of acid strength – a lower pKa means a stronger acid (which more readily donates protons).

When pH equals the pKa of an acid, what does that signify?

It means the acid is half dissociated: the concentrations of the acid [HA] and its conjugate base [A⁻] are equal. (At pH = pKa, a buffer has maximum capacity to neutralize added acid or base.)

What is the Henderson–Hasselbalch equation?

pH = pKa + log([A⁻]/[HA]). It relates the pH of a buffer solution to the pKa of the acid and the ratio of conjugate base ([A⁻]) to acid ([HA]) present.

What is a buffer?

A solution composed of a weak acid and its conjugate base (or a weak base and its conjugate acid) that resists changes in pH when small amounts of acid or base are added.

Why do buffer solutions resist changes in pH?

Because the weak acid/base pair can neutralize added acids or bases. If H⁺ is added, the conjugate base in the buffer will bind it, forming the weak acid; if OH⁻ is added, the weak acid will give up a proton to neutralize it. This prevents large swings in pH.

When is a buffer most effective?

Buffers work best around the pKa of the buffering acid (within approximately ±1 pH unit of pKa), where significant amounts of both the acid and conjugate base are present.

What is the general structure of an α-amino acid?

A central (α) carbon bonded to an amino group (–NH₃⁺), a carboxyl group (–COO⁻), a hydrogen atom, and a variable side-chain (R group).

In what form do amino acids exist at physiological pH (~7)?

As zwitterions – the amino group is protonated (–NH₃⁺) and the carboxyl group is deprotonated (–COO⁻), so the molecule has both positive and negative charges but an overall neutral charge.

What is the isoelectric point (pI) of an amino acid?

The pH at which the amino acid has no net charge (the positive and negative charges balance out). For amino acids with no ionizable side chain, pI is roughly the average of the pKa of the carboxyl group and the pKa of the amino group.

Which amino acids have nonpolar (hydrophobic) aliphatic side chains?

Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Isoleucine (Ile), Methionine (Met), and Proline (Pro) are nonpolar and hydrophobic (their R groups are hydrocarbons or bulky aliphatic structures).

Which amino acids have aromatic side chains?

Phenylalanine (Phe), Tyrosine (Tyr), and Tryptophan (Trp) have aromatic rings in their side chains. (Tyrosine’s phenolic –OH makes it somewhat polar, but it is still generally considered aromatic.)

Which amino acids have polar, uncharged side chains?

Serine (Ser), Threonine (Thr), Asparagine (Asn), Glutamine (Gln), and Cysteine (Cys) have polar but uncharged side chains (capable of hydrogen bonding; Cys has a thiol which can be deprotonated at high pH).

Which amino acids have positively charged (basic) side chains at pH 7?

Lysine (Lys, K) and Arginine (Arg, R) are positively charged at physiological pH (their side chains –NH₃⁺ and –NH₂⁺⁺, respectively). Histidine (His, H) is a weak base; its imidazole side chain (pKa ~6.0) can be either protonated or neutral around pH 7.

Which amino acids have negatively charged (acidic) side chains?

Aspartic acid (Asp, D) and Glutamic acid (Glu, E) have carboxylate side chains that are negatively charged at physiological pH (Aspartate and Glutamate).

Which amino acid is not chiral (achiral)?

Glycine – its R group is H, so the α-carbon has two identical H substituents, making it non-chiral.

Which amino acid has a cyclic side chain that connects to its amino nitrogen?

Proline – its side chain forms a five-membered ring by bonding to its own amino group, creating a secondary amine. This rigid ring structure restricts Proline’s conformations.

Which amino acid contains a thiol group and can form disulfide bonds?

Cysteine – it has a sulfhydryl (–SH) on its side chain. Two cysteine residues can oxidize to form a disulfide bond (–S–S–, cystine), which helps stabilize protein structure.

Which amino acid has an imidazole side chain and why is it important?

Histidine – it contains an imidazole ring with a pKa around 6.0. This allows it to exist in both protonated and deprotonated forms at physiological pH, making it important in enzyme active sites (it can accept or donate protons) and as a buffering residue.

What does the first law of thermodynamics state?

Energy is conserved. It cannot be created or destroyed, only converted from one form to another (the total energy of a closed system and its surroundings remains constant).

What does the second law of thermodynamics state?

The entropy (disorder) of the universe tends to increase. In any spontaneous process, the total entropy of the system plus surroundings increases.

What is enthalpy (ΔH)?

The heat content of a system at constant pressure. ΔH < 0 indicates an exothermic process (releases heat), while ΔH > 0 indicates an endothermic process (absorbs heat).

What is entropy (ΔS)?

A measure of disorder or randomness in a system. Processes that increase randomness have ΔS > 0. An increase in entropy of the system (or system + surroundings) tends to favor spontaneity.

What is Gibbs free energy (ΔG)?

The energy available to do work at constant temperature and pressure, defined by ΔG = ΔH – TΔS. It indicates spontaneity: ΔG < 0 for a spontaneous (exergonic) process, ΔG > 0 for a nonspontaneous (endergonic) process, and ΔG = 0 at equilibrium.

What does it mean when ΔG = 0 for a reaction?

The reaction is at equilibrium – there is no net change in reactant or product concentrations, and the forward and reverse reaction rates are equal.

How can cells drive an endergonic (ΔG > 0) reaction?

By coupling it to an exergonic (ΔG < 0) reaction so that the overall ΔG is negative. For example, many unfavorable reactions are driven by coupling them to ATP hydrolysis, which releases free energy.

What is a peptide bond and how is it formed?

A peptide bond is a covalent amide bond linking two amino acids. It forms through a condensation (dehydration) reaction between the carboxyl group of one amino acid and the amino group of another, releasing a molecule of water.

Why is the peptide bond planar and rigid?

Because of resonance between the carbonyl C=O and the amide C–N bond. This delocalization gives the C–N bond partial double-bond character, preventing rotation. As a result, the peptide bond (the C–N linkage) is planar and usually in a trans configuration.

Which bonds in a polypeptide backbone can rotate to allow protein folding?

The single bonds involving the α-carbon can rotate: the N–Cα bond (phi, φ) and the Cα–C (carbonyl) bond (psi, ψ) are rotatable, enabling different conformations. (The peptide C–N bond itself is not freely rotatable due to its partial double-bond character.)

What is the N-terminus and C-terminus of a peptide?

The N-terminus is the end of a peptide with a free amino group (NH₃⁺), and the C-terminus is the end with a free carboxyl group (COO⁻). By convention, amino acid sequences are written from the N-terminus to the C-terminus.

What is the primary structure of a protein?

The linear sequence of amino acids in the polypeptide chain (from N-terminus to C-terminus), held together by peptide bonds.

What is protein secondary structure?

Local folded structures of the polypeptide backbone stabilized by backbone hydrogen bonds. The main secondary structure elements are the α-helix and the β-sheet (plus connecting turns and loops).

What are the key features of an α-helix?

It is a right-handed helix with about 3.6 amino acids per turn and a rise of ~5.4 Å per turn. The C=O of each residue i hydrogen bonds with the N–H of residue i+4, creating a stable coil. Side chains project outward from the helix.

Describe the structure of a β-sheet.

A β-sheet is made of β-strands aligned next to each other, forming a sheet-like arrangement. Hydrogen bonds form between the C=O of one strand and the N–H of an adjacent strand. Strands can be antiparallel (opposite direction) or parallel (same direction). Side chains on β-strands alternate above and below the plane of the sheet.

What is the difference between antiparallel and parallel β-sheets?

In antiparallel β-sheets, adjacent strands run in opposite N→C directions, so hydrogen bonds between strands are nearly straight and optimal. In parallel β-sheets, adjacent strands run in the same direction, so the hydrogen bonds are diagonal/slightly skewed, making parallel sheets a bit less stable than antiparallel.

What is a β-turn (beta turn)?

A tight turn in a polypeptide chain that connects two secondary structure elements and reverses the chain’s direction. β-turns usually consist of 4 amino acids and are stabilized by a hydrogen bond between the carbonyl oxygen of residue i and the amide hydrogen of residue i+3. Glycine (flexible) and proline (which readily forms a kink) are often found in β-turns.

Which amino acid often disrupts α-helices and why?

Proline, because its side chain is bonded to its amino nitrogen, forming a rigid ring. This constraints the backbone φ angle and it lacks an amide hydrogen to participate in hydrogen bonding, so inserting proline causes a kink or break in an α-helix.

Give an example of a fibrous protein and its secondary structure.

α-keratin (found in hair, nails) is a fibrous protein composed of α-helices wound into a coiled-coil. Another example is silk fibroin, which is composed largely of layers of antiparallel β-sheets.

What is the structural motif of collagen?

Collagen consists of three polypeptide chains twisted together in a triple helix (a unique secondary structure). It has a repeating Gly–X–Y sequence (where X is often Pro and Y is often hydroxyproline). Glycine at every third position allows the three chains to pack tightly together, and the abundance of Pro/Hyp stabilizes the helix.

What is tertiary structure of a protein?

The overall three-dimensional folding of a single polypeptide chain. It includes how α-helices, β-sheets, and coils/loops pack together into a compact structure. Tertiary structure is stabilized by side-chain interactions (hydrophobic effects, hydrogen bonds, ionic bonds, van der Waals forces) and sometimes covalent bonds like disulfides.

What is quaternary structure of a protein?

The arrangement of multiple polypeptide chains (subunits) in a multi-subunit protein. Quaternary structure describes how individual subunits associate with each other and interact to form a functional protein complex.

How does the hydrophobic effect influence protein folding?

Nonpolar (hydrophobic) side chains tend to cluster in the interior of the protein away from water, while polar and charged side chains remain on the surface interacting with water. This hydrophobic core formation is a major driving force for protein folding, as it releases ordered water molecules and increases entropy of the solvent.

What types of interactions stabilize a protein’s tertiary structure?

A variety of interactions: hydrophobic interactions among nonpolar side chains in the core; hydrogen bonds between polar side chains (or with backbone groups); ionic interactions (salt bridges) between oppositely charged side chains; van der Waals contacts among tightly packed residues; and disulfide bonds (covalent links between cysteine residues) in some proteins.

What is a disulfide bond in proteins?

A covalent bond between two cysteine residues forming cystine (–S–S–). Disulfide bonds create loops or links in the polypeptide that can greatly stabilize a protein’s tertiary (or quaternary) structure. They commonly occur in secreted or extracellular proteins (e.g., insulin has disulfide bridges).

How do fibrous proteins differ from globular proteins?

Fibrous proteins are elongated, filamentous molecules that serve structural roles; they often consist of a single type of secondary structure repeated (and are usually insoluble in water). Globular proteins are compact, roughly spherical molecules that carry out dynamic functions (enzymes, transport, etc.); they have a mix of secondary structures and are generally water-soluble.

What is a protein domain?

A distinct structural and functional unit of a protein. A domain is a part of the polypeptide chain that can fold independently into a stable structure. Large proteins often consist of multiple domains, each contributing a specific function (e.g., binding, catalytic, regulatory domains).

Give an example of a protein with quaternary structure.

Hemoglobin is an example: it has four subunits (2 α and 2 β chains) assembled into a tetramer. The subunits work cooperatively in oxygen binding. Another example is DNA polymerase holoenzyme, which has multiple protein subunits working together.

What are the components of a nucleotide?

A nucleotide consists of three parts: a five-carbon sugar (ribose in RNA or deoxyribose in DNA), a nitrogenous base (a purine or pyrimidine), and one or more phosphate groups.

What is the difference between a nucleoside and a nucleotide?

A nucleoside is just a base attached to a sugar (no phosphate). A nucleotide is a nucleoside with one or more phosphate groups attached (for example, adenosine triphosphate (ATP) is a nucleotide).

Which bases are purines and which are pyrimidines?

Purines are Adenine (A) and Guanine (G) – they have a double-ring structure. Pyrimidines are Cytosine (C), Thymine (T), and Uracil (U) – they have a single-ring structure.

What are the key differences between DNA and RNA?

DNA contains deoxyribose sugar (lacking a 2'–OH group) and uses the bases A, G, C, and Thymine (T). RNA contains ribose sugar (with a 2'–OH) and uses A, G, C, and Uracil (U) in place of T. DNA is typically double-stranded, forming a stable double helix; RNA is usually single-stranded and can fold into various secondary structures. DNA is more stable (lack of 2'–OH makes it less prone to hydrolysis), whereas RNA is more chemically reactive and less stable.

What is Watson–Crick base pairing?

The specific hydrogen bonding between complementary bases in nucleic acids: In DNA, Adenine (A) pairs with Thymine (T) via 2 hydrogen bonds, and Guanine (G) pairs with Cytosine (C) via 3 hydrogen bonds. (In RNA, A pairs with Uracil (U) similarly to A–T.)

Describe the DNA double helix (B-form DNA).

DNA consists of two antiparallel strands (running in opposite 5'→3' directions) wound into a right-handed double helix. There are about 10 base pairs per helical turn. The sugar-phosphate backbones lie on the outside and the bases are on the inside, paired by hydrogen bonds (A with T, G with C). The double helix has a major groove and a minor groove along its length.

What forces stabilize the DNA double helix?

Hydrogen bonds between complementary base pairs hold the two strands together (A–T with 2 H-bonds, G–C with 3 H-bonds), and base stacking interactions (hydrophobic effects and van der Waals forces between adjacent base pairs) provide additional stability to the helix.

What are the major and minor grooves in DNA?

They are the two uneven grooves that spiral around the DNA helix. The major groove is the larger gap between the backbones and exposes base pair edges in a way that many DNA-binding proteins can read the sequence. The minor groove is the smaller gap on the opposite side of the helix. These grooves are important for protein–DNA interactions.

How can single-stranded RNA form secondary structures?

RNA, being single-stranded, can fold back on itself by complementary base pairing to form structures like hairpins or stem-loop structures. For example, an RNA hairpin forms when a region of the RNA folds so that complementary bases pair (forming a double-helical stem) with an unpaired loop at the end. These intramolecular base pairs often result in an A-form helix in the RNA’s double-stranded regions.

What are two common experimental techniques used to determine a protein's 3D structure?

X-ray crystallography and NMR spectroscopy are two common methods (with cryo-EM as a newer technique).

What types of interactions stabilize a protein's tertiary structure?

Hydrophobic interactions (hydrophobic core), hydrogen bonds, ionic bonds (salt bridges), van der Waals forces, and disulfide bonds.

What is a disulfide bond and how does it stabilize protein structure?

A disulfide bond is a covalent bond between two cysteine residues (forming cystine) that acts as a cross-link to stabilize a protein's folded structure.

Why do proteins fold with hydrophobic residues packed in the interior (forming a hydrophobic core)?

Burying hydrophobic side chains in the protein's interior away from water is energetically favorable. This hydrophobic effect is a major driving force for protein folding and stability.

What did Anfinsen's classic RNase A refolding experiment demonstrate?

A protein's amino acid sequence alone determines its native 3D structure. In Anfinsen's experiment, RNase A was completely denatured with urea and a reducing agent, then allowed to refold after removing those chemicals; it regained its activity, proving that the sequence dictates the native fold.

What is meant by a protein's "native" state versus "denatured" state?

The native state is the properly folded, functional form of a protein. The denatured state is the unfolded, non-functional form (with its normal secondary and tertiary structure lost).

What are some common ways to denature (unfold) a protein?

Applying heat, extreme pH, or chemical denaturants (like urea, guanidine, or SDS) can disrupt a protein's stabilizing interactions and cause it to unfold.

What is a protein's melting temperature (Tm)?

The temperature at which half of the protein molecules are unfolded and half remain folded. It indicates the protein's thermal stability.

What does it mean that protein folding/unfolding is "cooperative"?

It means proteins tend to unfold in an all-or-none fashion. Once part of the protein unfolds, the rest rapidly follows, resulting in a sigmoidal (S-shaped) unfolding curve.

What is protein quaternary structure?

Quaternary structure describes how multiple polypeptide chains (subunits) fit together in a multi-subunit protein.