L(I'veGivenUp). Exam 1 Study Guide from Chauncey thanks king

Why are lipids generally small molecular weight molecules rather than polymers?

Lipids do not make polymers from smaller repeating units, so they generally remain small molecular weight molecules.

Why are lipids described as a "wastebucket" taxon or classification?

Lipids are a miscellaneous group of molecules that vary greatly in structure but are generally classified as hydrophobic.

What are the three major lipid classes discussed in the notes?

Triglycerides, phospholipids, and steroids.

What are triglycerides made of?

Three fatty acids bound to a glycerol molecule.

What is the primary function of triglycerides?

Long-term fat storage.

How do triglycerides differ from free fatty acids in terms of charge?

Triglycerides are no longer charged ionic, although they are still polar.

How do phospholipids differ structurally from triglycerides?

One fatty acid chain is replaced with a phospho-containing head group.

Why are phospholipids highly polar compared with triglycerides?

The phospho-containing head group adds more charge to the glycerol side.

Why does the strong polarity of phospholipids allow them to form lipid bilayers?

Their strong polarity allows them to organize into phospholipid bilayers.

What structural feature defines steroids?

Steroids have a backbone or skeleton made up of four fused carbon rings.

Why are steroids highly non-polar compared with other lipid classes?

Their four-ring carbon skeleton and substituents give them a highly non-polar structure.

What are the two major functions of steroids discussed in the notes?

They serve as components of lipid bilayers, such as cholesterol, and as signaling molecules such as testosterone and estrogen.

What is a protein according to the notes?

A polymer made of many amino acids, generally greater than 80 amino acids, that provides structure and function to living things.

What are the three main parts of an amino acid backbone?

A carboxylic acid group, an amine group, and an R group or side chain attached to a central carbon.

What does the R group of an amino acid determine?

The R group is the side chain that differs with each amino acid.

What is special about the central carbon of most amino acids?

It is an sp3-hybridized carbon that is a stereocenter, except in glycine.

How do amino acids form a peptide chain?

The amino acids are monomers that bond together to form a peptide or peptide chain.

What interaction forms the amide between two amino acids?

The carboxylic acid of one amino acid interacts with the amine of another amino acid.

Why is the peptide bond relatively strong?

The resulting amide is a strong sp2-hybridized functional group that can only be broken by specific enzymes.

What are the three carbohydrate categories based on the number of carbohydrate units?

Monosaccharides, disaccharides, and polysaccharides.

What is the typical carbon range of carbohydrates described in the notes?

Usually 3-7 carbons.

What type of functional group is associated with one carbon in many carbohydrates?

An sp2 functional group such as an aldehyde or ketone.

What are the three major functions of carbohydrates?

Energy source, medium-term energy storage, and scaffold for nucleic acids.

How do polysaccharides contribute to carbohydrate function?

They provide medium-term energy storage.

How do ribose and deoxyribose relate to carbohydrates?

They serve as carbohydrate scaffolds for nucleic acids.

What are DNA and RNA made from?

They are polymers made from nucleotides.

What are the three components of a nucleotide?

A base, a sugar such as ribose or deoxyribose, and a phosphate group.

How do nucleotides form nucleic acid polymers?

Nucleotides bond through phosphate linkages.

Besides forming nucleic acids, what other functions can nucleotides have?

They can serve as energy molecules such as ATP and signaling molecules such as AMP, GTP, and CTP.

How are small molecules defined in the notes?

Small molecules have a molecular weight of less than 1000 g/mol.

Why were small molecule drugs historically dominant in pharmaceuticals?

Early medications were often natural extracts from plants that contained mixtures of small molecules, which could be extracted, separated, synthesized, and mass produced.

Why can small molecules readily act on targets inside cells?

Small molecules with the correct makeup can readily cross lipid bilayer membranes.

What is one major limitation of small molecules related to "undruggability"?

Some human proteins do not have active sites, binding pockets, or other accessible sites where conventional small molecules can act.

How can lack of specificity limit small molecule drugs?

Small molecules may act on targets other than the desired target, potentially causing side effects.

Why can small molecules have difficulty providing biological functions?

They cannot add missing biological functions or directly correct the underlying biology.

What are major advantages of small molecule drugs compared with biopharmaceuticals?

They are easy to manufacture at large scale, have excellent PK properties, cross membranes well, and are easy to detect and quantify in biological samples.

Why do biopharmaceuticals generally have more difficulty crossing membranes than small molecules?

The body is designed to keep biomolecules such as proteins, lipids, carbohydrates, and nucleic acids in their designated spaces.

What is a biopharmaceutical?

A pharmaceutical product made from biomolecules such as proteins, lipids, nucleic acids, or carbohydrates that can accomplish therapeutic interventions small molecule chemicals cannot.

What is a biologic or biologic product?

A medical product derived from living organisms or containing components from living organisms.

According to the FDA definition in the notes, when is a peptide not considered a biologic?

A peptide shorter than 40 amino acids is not considered a biologic by the FDA.

What is a chemical entity?

A chemical drug produced through chemical synthesis.

How does the US/FDA definition classify protein drugs containing fewer than 40 amino acids?

They are classified as chemical entities.

How does the EU/UK definition differ from the US/FDA definition for chemically made peptides?

The EU/UK definition considers chemically made peptides chemical entities, while peptides made through biotechnology are biologic products.

What does TIDES refer to?

Therapeutic intermediates involving drugs and entities with synthetic or designed chemistry, referring to pepTIDES and oligonucleoTIDES.

How does the FDA classification of peptides relate to the 40-amino-acid cutoff?

Peptides must be greater than 40 amino acids to be considered biologics by the FDA.

Why are GLP-1 agonists described as both biopharmaceuticals and chemical entities?

They are about 31 amino acids long, so they can be considered biopharmaceuticals and chemical entities but not biologics by the FDA definition.

What is an oligonucleotide?

A short chain of nucleotides or nucleotide analogs.

Why is inclisiran an example of an oligonucleotide?

Inclisiran is a short chain containing 23 nucleotides.

How are oligonucleotides classified by the FDA according to the notes?

They are considered biopharmaceuticals and chemical entities but not biologics.

What is gene therapy?

A therapy that seeks to modify or manipulate gene expression to alter biological properties of living cells for therapeutic use.

How are gene therapy agents classified?

Gene therapy agents are classified as biologic agents.

What are programmable biologic therapies?

Treatments involving biopharmaceutical molecules capable of correcting or rewriting biological systems.

What examples of programmable biologic therapies are given?

CAR-T cell therapy and CRISPR.

How did the focus of biopharmaceutical development change from the 1980s to about 2017?

The 1980s focused on biologic drugs targeting specific proteins, while around 2017 the focus shifted toward adding or correcting biological systems.

What defines a peptide drug according to the FDA definition?

A peptide drug contains fewer than 40 amino acids.

What approximate molecular weight range is given for peptide drugs?

About 500-5,000 g/mol.

What molecular weight range is given for a medium-sized protein?

About 20-50 kDa, or 20,000-50,000 g/mol.

What is the approximate molecular weight range given for oligonucleotide drugs?

About 7,000-15,000 g/mol.

What is the major advantage of biopharmaceuticals regarding complex targets?

They can interact with large or complex targets that traditional small molecules may not affect.

How can biopharmaceuticals provide biological function?

They can replace a missing protein, add or modify a biological function, or correct underlying biology.

Why do biopharmaceuticals generally have high molecular specificity?

Their molecular structures allow them to interact specifically with desired targets, unlike small molecules that may act on multiple targets.

What are major limitations of biopharmaceutical drugs compared with small molecules?

They are more difficult to manufacture, purify, and characterize; are less able to cross membranes; and are more fragile and complex.

What is diabetes mellitus?

A disease associated with abnormal regulation of blood glucose in which fully developed disease can lead to diabetic ketoacidosis, coma, and death.

What is Type 1 diabetes according to the notes?

An autoimmune disease in which immune cells attack pancreatic cells that make insulin, resulting in lower insulin levels.

What is the major treatment for Type 1 diabetes stated in the notes?

Insulin injections.

What characterizes Type 2 diabetes?

Insulin resistance, in which the body makes a normal amount of insulin but cells stop responding to it properly.

What type of molecule is insulin?

A small protein or peptide endocrine hormone.

Where is insulin secreted?

Insulin is secreted by beta cells in the pancreas.

What happens when blood glucose levels rise?

The pancreas releases insulin into the bloodstream, and insulin signals cells to take in glucose.

Where is the insulin receptor located?

On the cell surface.

Why can a small molecule not replace insulin?

The insulin receptor requires a large protein-protein interaction that cannot be produced by a small molecule under 1000 g/mol.

What can happen when cells cannot properly take in glucose because of insufficient insulin?

Cells perform metabolic processes that create toxic byproducts, which enter the bloodstream and can lead to diabetic ketoacidosis.

Where is the insulin gene located?

On chromosome 11.

What is the first step in insulin biosynthesis?

Transcription of DNA at the insulin gene into pre-mRNA inside beta cells.

What is the sequence of the early insulin genetic process?

DNA → pre-mRNA → mature mRNA.

What happens during RNA splicing in insulin biosynthesis?

Parts of the mRNA copied from DNA introns are removed.

What does mature insulin mRNA encode after RNA splicing?

A 110-amino-acid chain called preproinsulin.

What happens during translation of insulin?

The mature mRNA moves to the cytoplasm, a ribosome forms on the mRNA, and tRNAs bring amino acids that match the mRNA codons to form the growing peptide chain.

What are the four functional components of preproinsulin?

A signal peptide, A chain, B chain, and C-peptide.

What happens to the signal peptide during conversion of preproinsulin to proinsulin?

The signal peptide directs the molecule to the ER and is then removed, converting preproinsulin into proinsulin.

Where do disulfide bonds form during insulin biosynthesis?

Disulfide bonds form while proinsulin is in the endoplasmic reticulum.

What happens to proinsulin after it reaches the Golgi apparatus?

It is stored into vesicles.

What is the role of C-peptide in proinsulin?

C-peptide acts as a linking unit between the A and B chains.

How is mature insulin formed from proinsulin?

Enzymes cleave out the C-peptide, leaving the A and B chains connected by disulfide bonds.

What is a gene?

A unit of DNA that codes for a protein.

What are exons?

What are introns?

EXONS - Parts of a DNA sequence that code for a protein.

INTRONS - Parts of a DNA sequence that help regulate genes but do not code for proteins.

What is transcription?

The process of copying DNA information into mRNA.

What is RNA splicing?

The removal of parts of mRNA that came from copying DNA introns.

What is translation?

The process in which mRNA is used to produce a protein.

What role does the ribosome play in translation?

The ribosome recruits tRNAs carrying amino acids that match codons on the mRNA and adds those amino acids to the growing peptide chain.

What is proteolysis?

Hydrolytic cleavage of peptide bonds.

What are proteases or peptidases?

Enzymes that break down proteins or peptides into smaller components.

What is protein processing?

Using proteolysis through a protease or peptidase to convert a protein precursor into its active form.

What is a post-translational modification?

A change made to a protein after translation, including cleavage, folding, phosphorylation, or formation of protein-protein disulfide bonds.

What is a disulfide bond?

A covalent bond between the sulfur atoms of two cysteine amino acid residues.

What functional group forms the peptide bond between two amino acids?

An amide.

How is an amide or peptide bond formed?

The amine of one amino acid acts as a nucleophile and attacks the carboxylic acid of another amino acid, forming a new C-N bond.

Why are amide peptide bonds considered strong?

They can resist high temperatures and high acidity and generally require specific enzymes to break them.

How can a peptide bond participate in hydrogen bonding?

The NH portion can act as a hydrogen bond donor and acceptor, while the oxygen acts as a hydrogen bond acceptor.

What produces secondary structure in proteins?

Hydrogen bonding between amides in the same peptide chain.