Aminoácidos y Proteínas - Biología Celular y Tisular

Introduction to Biomolecules and Amino Acids

Overview of Biomolecules

• The class focuses on amino acids and proteins, introducing the concept of biomolecules that form all biological systems, from bacteria to humans.

• Biomolecules are primarily composed of carbon, hydrogen, oxygen, nitrogen, sulfur, and phosphorus. Their structure is defined by chains of carbon atoms and functional groups that influence their function.

Types of Carbon Chains

• Carbon chains can be linear (aliphatic compounds) or cyclic (aromatic compounds), each having distinct properties.

• Functional groups such as aldehydes, ketones, carboxylic acids (containing carbon and oxygen), sulfites (containing sulfur), and amino groups (containing nitrogen) contribute to the identity and functionality of biomolecules.

Functions of Biomolecules in Cells

Structural and Metabolic Roles

• Biomolecules serve various functions within cells: structural roles include forming biological membranes and cytoskeleton; metabolic roles involve energy provision through biochemical pathways.

• This class specifically addresses amino acids as the basic units that make up proteins.

Essential vs Non-Essential Amino Acids

Classification of Amino Acids

• There are 20 natural amino acids that constitute proteins across all known organisms. Some are essential for certain organisms like humans.

• Essential amino acids cannot be synthesized by the body; they must be obtained through diet. For example, phenylalanine is essential while tyrosine is not because it can be synthesized from phenylalanine.

Synthesis Capabilities in Organisms

• Different organisms have varying capabilities for synthesizing these amino acids; for instance, Escherichia coli can synthesize all 20 without external sources.

Non-canonical Amino Acids

Post-translational Modifications

• Beyond the standard 20 amino acids, there exist non-canonical ones formed through post-translational modifications like hydroxylation or phosphorylation which play significant roles in signaling pathways.

Structure of Amino Acids

Basic Structure Components

• Each amino acid consists of an amino group (-NH2), a carboxylic acid group (-COOH), a hydrogen atom attached to a central carbon (alpha-carbon), and a variable side chain denoted as R-group which defines each specific amino acid's identity.

Chirality in Amino Acids

• The alpha-carbon is chiral or asymmetric due to its attachment to four different substituents leading to two enantiomers for most amino acids.

• These enantiomers are mirror images known as isomers; L-form predominates in natural proteins while D-form occurs less frequently.

Ionization Properties of Amino Acids

Acid-base Behavior

Properties of Amino Acids and Their Ionization

Group R and Its Influence on Properties

• The properties of the R group in amino acids can determine whether they behave as acids or bases, depending on their identity.

• The equilibrium between protonated (protonated form) and deprotonated (deprotonated form) states is described by an acidity constant, with a specific pKa value indicating the pH at which both forms are present equally.

pH Effects on Amino Acid Forms

• At physiological pH (7.4), carboxyl groups are predominantly found in their deprotonated state, while amino groups remain mostly protonated due to their higher pKa values.

• This results in amino acids existing in different ionic forms based on the surrounding pH; for instance, at lower pH levels, all groups may be fully protonated.

Zwitterions and Charge Neutrality

• Amino acids can exist as zwitterions, possessing both positive and negative charges but overall neutral charge due to balancing +1 and -1 charges.

• This unique structure allows them to act as weak acids with two protons available for dissociation.

Titration Curves of Amino Acids

• A titration curve illustrates how an amino acid behaves like a weak acid with two distinct equilibria represented by two pKa values.

• For glycine specifically, its non-ionizable R group leads to distinct behavior across varying pH levels: below 2.3 it exists fully protonated; between 2.3 and 9.6 it is primarily in zwitterionic form; above 9.6 it becomes fully deprotonated.

Isoelectric Point Calculation

• The isoelectric point (pI), where the amino acid has no net charge, can be calculated as the average of its two relevant pKa values.

• For non-ionizable side chains like glycine, this calculation provides insight into its behavior at physiological conditions.

Classification of Amino Acids Based on Polarity

Solubility and Interaction with Water

• All amino acids are soluble in water due to their carboxyl and amine groups; however, R groups vary significantly in polarity affecting solubility.

Nonpolar vs Polar Amino Acids

• Nonpolar aliphatic amino acids consist solely of carbon chains without charged functional groups; examples include proline and isoleucine which do not interact well with water.

Polar Amino Acids Without Net Charge

• Polar amino acids possess functional groups that can interact with water despite having no net charge; threonine's hydroxyl group exemplifies this property.

Hydrogen Bonding Among Polar Amino Acids

• Polar interactions among these amino acids occur through hydrogen bonding, crucial for protein structure stability during folding processes.

Unique Characteristics of Specific Amino Acids

Cysteine's Role in Protein Structure

• Cysteine contains a thiol (-SH group), allowing it to form disulfide bonds when reacting with another cysteine molecule—important for stabilizing protein structures.

Aromatic Amino Acids' UV Absorption

Understanding Amino Acids and Their Interactions

Properties of Amino Acids

• Amino acids can form interactions through stacking when arranged in layers, which is crucial for protein structure. Acidic amino acids possess ionizable groups with low pKa values, making them protonated at physiological pH.

• Basic amino acids have high pKa values due to their basic side chains, remaining protonated at physiological pH. Both acidic and basic amino acids are hydrophilic and can interact with water, forming ionic interactions with oppositely charged counterparts.

Ionization of Amino Acids

• The presence of additional functional groups in the side chain of an amino acid affects its ionization state. For example, glutamate has a carboxyl group in its side chain that influences its behavior depending on the pH.

• At different pH levels, glutamate can exist in various forms based on the protonation states of its functional groups. As pH increases, the most acidic group (alpha-carboxyl) loses a proton first.

Charge States and Isoelectric Point

• Glutamate exhibits four distinct forms depending on the surrounding pH; these include fully protonated to fully deprotonated states. The isoelectric point (pI) is calculated between specific pKa values where net charge equals zero.

• The dipolar ion form of glutamate shows both positive and negative charges; calculating the average of adjacent pKa values helps determine the isoelectric point.

Example: Lysine Ionization

• Analyzing lysine's ionization involves identifying three key pKa values associated with its functional groups. The order of deprotonation follows increasing acidity from carboxyl to amine groups.

• After determining all possible ionized forms for lysine, one calculates its dipolar form to find out whether it carries a positive or negative charge at given pH levels.

Peptide Bond Formation

• Amino acids link together to form proteins via peptide bonds through a covalent reaction between an alpha-carboxyl group of one amino acid and an alpha-amino group of another.

Understanding Protein Structure and Function

The Basics of Peptides and Proteins

• Peptides are chains of amino acids linked by peptide bonds, which restrict mobility due to their rigid structure. This rigidity affects the overall flexibility of protein chains.

• When two amino acids bond, they form a dipeptide; multiple amino acids create polypeptides. Short chains are called oligopeptides, while longer ones are termed polypeptides.

• Proteins consist of numerous amino acids (polypeptides), sometimes comprising hundreds. For example, a peptide with five amino acids is highlighted in the discussion.

Examples and Functions of Proteins

• Aspartame, a sweetener formed from aspartic acid and phenylalanine, is significantly sweeter than table sugar (sucrose).

• Cytochrome c is an example of a protein found in mitochondria that consists of around 100 amino acids. Enzymes can contain thousands of amino acids.

Structural Levels of Proteins

Primary Structure

• The primary structure refers to the sequence and order of amino acids in a chain, which determines the identity and function of the protein based on genetic coding.

Secondary Structure

• Secondary structures arise from local arrangements within the polypeptide chain, stabilized by hydrogen bonds between atoms in peptide bonds.

• Common secondary structures include alpha helices and beta sheets. A single protein may exhibit various secondary structures across different segments.

Tertiary Structure

• Tertiary structure describes how secondary structures fold into three-dimensional shapes influenced by interactions among side chains (R groups).

Detailed Examination of Secondary Structures

Alpha Helices and Beta Sheets

• An alpha helix forms when a polypeptide chain coils around an imaginary axis, stabilized by hydrogen bonds every four amino acids.

• Beta sheets occur when segments align linearly, forming hydrogen bonds either within the same protein or between different proteins.

Beta Turns

• Beta turns facilitate connections between strands in beta sheets through interactions between opposing residues across folds in the polypeptide chain.

Protein Structure and Function

Secondary Structures and Biological Properties

• Proteins acquire secondary structures in space, which contribute to the overall global structure of the protein, influencing its biological properties and functions.

Interactions Between Amino Acids

• Weak interactions such as hydrogen bonds, ionic interactions, dipole-dipole interactions, and hydrophobic interactions play a crucial role in how amino acids interact within a protein's structure.

Quaternary Structure Example: Hemoglobin

• Hemoglobin is an example of a quaternary structured protein composed of four subunits held together by weak bonds. In contrast, myoglobin is a monomeric protein without quaternary structure.

Types of Proteins: Fibrous vs. Globular

• Fibrous proteins (e.g., keratin) provide structural support and mechanical resistance, while globular proteins (e.g., enzymes) have regulatory functions. Examples include collagen for fibrous proteins and various globular proteins involved in transport or defense.

Protein Folding Mechanism

• The folding process of a protein is determined by its primary structure (amino acid sequence). Initially unfolded proteins are unstable; as they fold into secondary and tertiary structures, they stabilize into their native conformations with relevant biological properties.

Role of Chaperones in Protein Folding

• Molecular chaperones assist in proper protein folding by providing cavities for folding processes. They may utilize ATP hydrolysis energy to facilitate this process effectively.

Impact of Mutations on Protein Function

Case Study: Sickle Cell Anemia

• Sickle cell anemia arises from a genetic mutation affecting hemoglobin where one amino acid (glutamic acid) is replaced by another (valine), leading to insoluble aggregates that deform red blood cells.

Analysis of Amino Acid Substitution

• The mutation results in altered electrical properties due to the loss of charge when glutamic acid is substituted with valine. This change can significantly impact the functionality of the hemoglobin molecule.

Calculating Isoelectric Points

• To analyze glutamic acid's behavior post-mutation, calculations regarding its ionization states are necessary to determine its isoelectric point based on acidic groups present.

Conservativeness of Mutations