Protein structure and function

• All amino acids that the body needs are important
• Not all amino acids that enter the body are used to synthesize proteins; some have other functions

Objectives

• Define amino acids, and describe their general structure
• Classify amino acids based on their chemical, biological, and metabolic properties
• Differentiate between essential, non-essential, and conditionally essential amino acids
• Describe the different levels of protein structure
• Explain the concept of protein misfolding and its role in diseases like Alzheimer's, Parkinson's, and prion diseases
• Discuss the significance and applications of protein denaturation in biological and medical contexts
• Identify the types of bonds stabilizing protein structures
• Describe the classification of proteins

What Are Proteins?

• Proteins are organic nitrogenous compounds consisting of L-alpha-amino acids united by peptide linkages
• Proteins are composed of carbon, hydrogen, oxygen, and nitrogen; many also contain sulfur
• Nitrogen is a characteristic component, forming 16% of protein weight

Biological Importance of Proteins

• Proteins play a nutritional role
• Proteins play a catalytic role as all enzymes are proteins in nature
• Most hormones and all cellular receptors are protein in nature
• Antibodies (immunoglobulins) are defensive proteins playing a key role in the body's defensive mechanisms
• Plasma proteins are responsible for the effective osmotic pressure of the blood

Amino Acids

• Amino acids are organic acids containing an amino group and a carboxylic group (COOH)
• They serve as the building units of proteins
• Mammals have L-amino acids where the amino group is on the left side configuration
• A carboxylic group (COOH) and an amino group (NH2) are both attached to the α-carbon.
• Each amino acid has a characteristic side chain (R)
• Although approximately 500 amino acids exist in nature, only 20 can polymerize in protein structures
• There is a specific codon in the genetic code for each amino acid
• All amino acids are optically active, except glycine

Functions of Amino Acids

• Protein synthesis: building blocks for protein, essential for growth, repair, and maintenance
• Enzyme and hormone production: many are made from amino acids like insulin and glucagon, and regulate metabolic processes
• Neurotransmitter synthesis: some amino acids are precursors to neurotransmitters, for example, tryptophan for serotonin and tyrosine for dopamine
• Immune function: certain amino acids like glutamine and arginine support immune cell function/response
• Acid-base balance: amino acids maintain pH balance by acting as buffers
• Transport and storage of nutrients: such as albumin and hemoglobin transport molecules like oxygen, iron, and nutrients
• Wound healing and tissue repair: Amino acids like arginine and proline promote collagen formation and tissue healing
• Detoxification: amino acids assist in removing toxins from the body such as is seen in the urea cycle
• Signaling molecules: amino acids and their derivatives function as cell signaling molecules, for example, nitric oxide from arginine
• Energy production: amino acids can be used as an energy source through gluconeogenesis or direct oxidation when needed

Nomenclature

• Each amino acid has a three-letter abbreviation and a one-letter code

Classification of Amino Acids

• Amino acids are classified based on (A) chemical, (B) biological/nutritional, and (C) metabolic classifications
• Chemical classification is based on the number of amino groups or carboxyl groups
• Chemical classification includes neutral, acidic, and basic amino acids
• Biological/nutritional classification is based on whether the amino acids can be synthesized in the human body or not
• The types of biological/nutritional classification include essential and non-essential amino acids
• Essential amino acids cannot be synthesized and must be supplied in the diet
• Non-essential amino acids are synthesized, so they don't need to be present in the diet
• Metabolic classification is based on the fate of the amino acid inside the body
• The types of metabolic classification include: glucogenic, ketogenic, and mixed amino acids
• Glucogenic amino acids can be converted to glucose
• Ketogenic amino acids can be converted to ketone bodies
• Mixed amino acids can be converted to glucose and ketone bodies

Neutral Amino Acids

• Neutral amino acids contain one amino group and one carboxyl group
• Classes of neutral amino acids:
  • Aliphatic: straight or branched hydrocarbon side chains without rings (glycine, alanine, valine, leucine and isoleucine)
    • Non-polar and hydrophobic, so they are found in protein structure away from water
    • Branched chain amino acids: valine, leucine and isoleucine
  • Hydroxy: contain -OH groups (serine and threonine)
    • Polar
  • Sulfur-containing: contain sulfur atoms (cysteine, homocysteine, cystine, and methionine
  • Aromatic: contain aromatic rings (phenylalanine, tyrosine, and tryptophan)
  • Heterocyclic: contain rings other than benzene (tryptophan, histidine, and imino acids (proline and hydroxyproline))

Acidic Amino Acids

• Acidic amino acids contain two carboxyl groups and one amino group (Glutamic acid and Aspartic acid)

Basic Amino Acids

• Basic amino acids contain one carboxyl group and two amino groups (Arginine, Citrulline, Ornithine, Lysine and Hydroxylysine)

Metabolic Classification

• They are classified based on the metabolic fate of the amino acids, whether they are converted into glucose or ketone bodies
• Glucogenic amino acids can be converted into glucose
• Examples of Glucogenic amino acids: Alanine, Aspartate, Serine, Glycine
• Ketogenic amino acids can be converted into ketone bodies or acetyl-CoA
• Leucine is the only pure ketogenic amino acid
• Both glucogenic and ketogenic (Mixed) amino acids can be metabolized into both glucose and ketone bodies, depending on the conditions
• Examples of Glucogenic and Ketogenic Amino Acids: Lysine, Isoleucine, Phenylalanine, Tyrosine, and Tryptophan

Biological or Nutritional Classification

• They are classified based on their nutritional requirements
• Essential amino acids cannot be synthesized and must be obtained through diet, muscle building, enzyme function, hormone synthesis, and tissue repair
• Source: animal proteins (milk, egg, meat, liver, fish, chicken) and a few plant proteins (bean and lintels)
  • Valine, Isoleucine, Threonine, Tryptophan, Arginine, Leucine, Lysine, Methionine, Phenylalanine, Histidine
• Conditionally essential amino acids are non-essential under normal conditions but can become essential during times of stress, illness, or metabolic disorders
• May occur when the body may not be able to synthesize these amino acids in sufficient amounts during illness or trauma
  • Arginine and histidine are examples
• Non-essential amino acids can be synthesized by the body from other molecules, and their deficiency does not affect growth or health. -The rest of amino acids fall into this category