BIOL 1101 FINAL

Opioid Receptors

Receptors on the surface of neurons that bind opioid drugs (ex. fentanyl, heroin, and naloxone) and is an integral membrane protein

Naloxone (Narcan)

An opioid receptor antagonist that binds the mu-opioid receptor without activating it, blocking fentanyl and heroin.

Antagonist

A molecule that binds to a receptor but does not activate it, blocking agonists from binding.

Heroin

An opioid agonist that activates the mu-opioid receptor but induces weaker and less dangerous signaling than fentanyl.

Fentanyl

A powerful opioid agonist that binds strongly to the mu-opioid receptor, causing intense signaling and high risk of respiratory depression.

Agonist

A molecule that binds to a receptor and activates it, turning on downstream signaling.

Mu-opioid receptor

A specific opioid receptor on neurons responsible for pain relief, respiratory depression, etc

Heroine, fentanyl, and naloxone bind to receptors on cells and cause different effects blc they…

Bind to the same receptors but cause different effects

How do fentanyl and heroin affect cells?

They act as ligands (molecules that bind to proteins) and bind to mu-opioid receptors on the outside of cells, this changes the receptor’s shape and triggers a signaling cascade inside the cell.

Fentanyl is so dangerous because it…

Particularly depresses respiration

A covalent bond

Shares electrons between two atoms

How many covalent bonds can a carbon atom make?

4

Pick the specific region on the fentanyl molecule that might explain why fentanyl has more potent negative effects than heroin

Non-polar ring that may be able to get inside of the pore of the protein more and interact with it there

Sickle Cell Anemia

A disorder caused by a single amino acid substitution (valine) in beta-hemoglobin that alters protein structure

Molecule

Multiple atoms held together by shared electrons

Polar

Uneven sharing of electrons (asymmetrical, ex. H2O)

Non-polar

Even sharing of electrons (symmetrical)

Property of forming hydrogen bonds in water

High cohesion, ability to exclude uncharged molecules, and ability to resist rapid temperature change

Covalent bond

Shared electrons between atoms ( electrons can be shared evenly/unevenly)

Structure of Sugars

Ring structures

Structure of Lipids

Long chains

Structures of peptides/proteins

Branching structures

Substances composed heavily of C and H (lacking other atoms)..

Crowd away from water (ex. oils, fats, lipids)

Hydrophobic molecules

“Water fearing”, want to interact w/themselves and shield themselves away from water

Why is water unique at ambient temperatures?

Resists rapid temperature change, dissolves many substances, excludes some molecules, and is cohesive (can be pulled/pushed in columns).

Hydrolysis

Uses water to break a bond (adds a water molecule)

Which parts of an amino acid participates in peptide bond formation?

Formed between the nitrogen of one amino group and the carboxyl group of another amino acid.

Macromolecules

Formed of repeating smaller (subunits), si

Macromolecules

Formed of repeating smaller units (subuntis) covalently bonded; four classes: proteins, nucleic acids, carbohydrates, and lipids

Polypeptides

Strings of amino acids residues connected by peptide bonds

Protein

Is a macromolecule formed on one or more polypeptides

Primary structure

The specific sequence of amino acids making up a polypeptide chain, from amino to carboxyl termini

Secondary structure

Either an alpha helix/beta pleated sheet (is generated by H-bonding in backbone of polypeptides/peptide)

SIDE CHAINS DO NOTHING

What drives protein shape in living organisms through polypeptide amino acid residue side chains?

Non-covalent bonds (ionic, H-bonding, van der Waals forces) and the hydrophobic effect

Denaturation

Break non-covalent bonds

Non-covalent bonds (electrostatic interactions)

Does not involve sharing of electrons, gives molecules structural flexibility: hydrogen bonding, ionic bonding, van der Waals interactions, hydrophobic interactions

T or F If water were less polar: increased cohesion would contribute to increased upward water transport potential in plants

FALSE: Cohesion: water molecules stick together because of hydrogen bonding and how transpiration happens where water goes up the plants (less polar = less sticky).

Why is “big” better for molecules?

• Storage (energy, info)

• Build/attach, construct bigger things

• Bring things together, make stuff happen

Nucleotide

Monomer/building block of nucleic acids made up of a 5-carbon sugar, a phosphate group, & a nitrogenous base

Monosacchardie

A sugar (ex. glucose)

The -R group

An amino acid polymer

A peptide/polypeptide

Polymer of amino acids, identify the alpha carbons and peptide bonds

Alpha carbons highlighted in blue, peptide bonds highlighted in yellow

Polymers

Made from covalently attaching monomers together in repeating reactions

Polymerization

Small molecules (monomers), chemically bond together to form large, chain-like molecules (polymers) - ex. dehydration (condensation)

Dehydration (condensation)

Removes a water molecule, forming a new bond

Depolymerization

The process of reacting monomers together to form 3-D networks of polymer chains (polymer gets shorter) - ex. hydrolysis

Tertiary structure

Whole polypetide will fold upon itself (one polypeptide)

Quaternary structure

Binding/folding of multiple polypeptides into a single protein

Outside cells are what type of bond?

Covalent bond (ex. Cysteine disulfide bonds)

Peptide bonds

Covalent bond between amino acids, the carboxyl group of one amino acids shares electrons with amino group of another amino acid. (generates potential for hydrogen bonding)

Which structures do the side-chain non-covalent bonds play an important role?

Teritarry & Quaternary structures

Hydrophilic

“Water-loving”, want to interact with water (polar/ionic molecules)

General protein structure follow 2 rules:

1. Hydrophobic residues are buried in protein interior, away from water.

2. The # of H-bonds within the protein is maximized.

What type of bond links amino acids together in primary structure?

Peptide bond

What type of bond stabilizes the local folding of a polypeptide into a beta sheet

Hydrogen bond

Where are non-polar R groups generally

In the interior of folded proteins

What type of bond stabilizes secondary structure?

Hydrogen bond

In sickle cell disease, beta-hemoglobin contains (blank) at amino acid position 6

Valine

CFTR protein

A receptor in the membrane, folded in ER and go to membrane of cell

If CTFR is misfolded what happens to the peptide?

Peptide never leaves ER, and is degraded by “quality control” enzymes

Phospholipids

Are amphiphilic, they have polar heads and non-polar tails. Composed of a glycerol backbone, a phosphate group, & 2 fatty acid chains

Glutamic Acid

Contains 2 oxygens, carries a full charge at physiological pH (anion), interacts favorably w/water

Valine

Composed of carbons and hydrogens, non-polar and hydrophobic, unfavorable interaction w/water

T or F: More double bonds in fatty acid tails increases fluidity

TRUE: . they introduce "kinks" in the hydrocarbon chains, which prevent them from packing tightly together.

T or F: Longer tail length of fatty acids increases fluidity

FALSE: longer fatty acid chain lengths decrease membrane fluidity and make the membrane more rigid since it increases surface area for intermolecular interactions.

How might a yeast cell adjust the contents of its cell membrane to protect itself from a sudden increase in temperature?

It might increase the # of long-chain fatty acids, number of sterols, and # of saturated fatty acids in its membrane

Saturated fatty acid

A fatty acid with no double bonds, making it straight and rigid.

Unsaturated fatty acid

A fatty acid with one or more cis double bonds, creating “kinks”.

Cholesterol (steroids)

A lipid, it can affect the fluidity of cell membrane

What is generally found in the bilayer of cell membrane

Phospholipids, sterols, integral proteins, glycolipids, and lipid rafts

Carbohydrates like those on glycolipids and glycoproteins are found

On the exterior of the cell membrane

Cell signaling pathway

A series of liked molecular interactions and reactions

Heterotrimeric G proteins

Can operate as molecular signaling switches and have alpha, beta, and gamma subunits

Hydrophobic signaling molecules

Can pass right through the membrane rather than use a cell-surface receptor

How to activate/promote cell cycle

Cyclin

Apoptosis

Programed cell death

Endocrine signaling

Long-distance cell-to-cell communication where specialized endocrine cells or glands secrete hormones into the bloodstream.

Paracrine signaling

Local cellular communication where a cell produces signaling molecules (ligands) that induce changes in nearby target cells within the same tissue

Autocrine singaling

Signal that is sent and received by the same or similar nearby cells.

“Juxtacrine” signaling

Occurs when signaling molecules on the surface of one cell interact with receptors on an adjacent cell.

Synaptic cleft

Space between neurons

Ligands

The signaling molecules that bind receptors

Examples of receptors that interact with cell surface

Adrenaline signaling, growth factor signaling

Examples of receptors that enter cell to interact with intracellular receptor

Steroid signaling (estrogen, cortisone)

Liver physiological response

Breakdown of glycogen and release of glucose into bloodstream

Adrenaline (epinephrine)

Signaling ligand that is a small polar molecule and signals through endocrine signaling responding cells in the liver

Adrenergic receptors

GPCrs found on cell surface that bind epinephrine/norepinephrine and trigger a signaling response.

GPCRs

G-protein coupled receptors. GPCRs work by producing lots of secondary messengers

Protein Kinase A (PKA)

Enzyme activates enzymes that release glucose from glycogen stores

Consequence of phosphorylation of proteins

Changes rate of heart muscle contraction/liver cell release glucose

During transmission of signals inside cells..

The signal is amplified and spread

Signal Amplification

A process where one ligand binding to a receptor triggers a cascade that activates many downstream enzymes/second messengers

How are signals turned off and “reset”?

Often through protein dephosphorylation (phosphatases) = removal of phosphate group

Signaling pathways must be turned (blank)

OFF to ensure proper cellular regulation, homeostasis, and recovery for future signals

G Proteins

Breaking a phosphodiester bond in GTP turns it into GDP (no protein kinase/phosphatase here)

What are the steps of the adrenaline GPCR signaling pathway?

Adrenaline binds GPCR → G protein activated (GTP binds) → adenylyl cyclase activated → cAMP produced → PKA activated → proteins phosphorylated → cellular response

Why is amplification important in adrenaline signaling?

Allows a small amount of concentration to produce a large response

What is the structure and function of GPCRs?

Seven transmembrane domains (crosses over membrane), the ligands bind on the outside, causing a conformational change inside the cell to transmit a signal.

Activating receptors leads to…

Conformational change