genomics final

ACD (Accidental Cell Death)

A form of cell death caused by severe injury or physical/chemical trauma (e.g., burns, freeze-thaw), resulting in membrane compromise and necrosis.

RCD (Regulated Cell Death)

A genetically controlled form of cell death (e.g., apoptosis) triggered by specific molecular signals to maintain homeostasis.

What are the main physiological functions of apoptosis?

Tissue development, immune system maturation (eliminating autoreactive cells), neural development, and tissue repair.

Efferocytosis

The process by which phagocytic cells remove dead or dying cells.

Phosphatidylserine (PS)

A lipid normally found on the inner leaflet of the plasma membrane that flips to the outer leaflet during apoptosis to serve as an "eat me" signal.

Annexin V

A protein used in assays to detect apoptotic cells by binding to exposed Phosphatidylserine (PS).

Extrinsic Apoptosis Pathway

The apoptotic pathway initiated by external signals (death ligands) binding to cell surface death receptors.

Intrinsic Apoptosis Pathway

The apoptotic pathway initiated by internal stress (DNA damage, oxidative stress) leading to mitochondrial dysfunction.

Which caspase is the initiator in the Extrinsic pathway?

Caspase-8

Which caspase is the initiator in the Intrinsic pathway?

Caspase-9

Caspases

Proteases with a cysteine in their active site that cleave target proteins at specific aspartic acid residues.

Procaspase

The inactive zymogen form of a caspase that requires cleavage to become active.

Apoptosome

A complex formed by Cytochrome c, Apaf-1, and Procaspase-9 that activates Caspase-9 in the intrinsic pathway.

Cytochrome c

A protein released from the mitochondrial intermembrane space into the cytosol to trigger the intrinsic apoptosis pathway.

Bcl-2 Family

A family of proteins that regulate mitochondrial membrane permeability, classified into pro-apoptotic and anti-apoptotic members.

Bcl-2 and Bcl-xL

Anti-apoptotic proteins that prevent cytochrome c release.

Bax and Bak

Pro-apoptotic proteins that form pores in the mitochondrial outer membrane to release cytochrome c.

BH3-only proteins (e.g., Bad, Bid, Puma)

Pro-apoptotic proteins that inhibit anti-apoptotic Bcl-2 members or directly activate Bax/Bak.

The pathway is triggered by DNA damage and p53 activation.

Intrinsic

The pathway is triggered by ligands like TNF-alpha or FasL.

Extrinsic

Perforin/Granzyme Pathway

A method used by cytotoxic T cells to kill target cells; perforin forms pores and granzyme B activates caspases.

p53

A tumor suppressor protein that accumulates in response to DNA damage and induces cell cycle arrest or apoptosis.

Mdm2

A ubiquitin ligase that normally keeps p53 levels low by targeting it for degradation; it is inactivated upon DNA damage.

Necrosis

A form of unregulated cell death characterized by cell swelling, membrane rupture, and inflammation.

How does apoptosis differ from necrosis regarding inflammation?

Apoptosis is non-inflammatory (clean removal), while necrosis causes inflammation due to release of intracellular contents.

Pyroptosis

A highly inflammatory form of regulated cell death often associated with infection and the release of cytokines like IL-1beta.

Ferroptosis

An iron-dependent form of regulated cell death characterized by lipid peroxidation.

Autophagy

A "self-eating" process where cells degrade their own components via lysosomes; can be a survival mechanism or lead to death.

Ruxolitinib (Jakafi)

A drug that acts as an ATP-competitive inhibitor of JAK1/2, used for blood disorders and inflammation.

Mechanism of Action for Adalimumab (Humira)

A monoclonal antibody that binds to TNF-alpha, preventing it from activating NF-kB signaling and reducing inflammation.

G-Protein Coupled Receptors (GPCRs)

The largest family of cell-surface receptors that activate intracellular G-proteins upon ligand binding.

Receptor Tyrosine Kinases (RTKs)

Cell surface receptors that dimerize and autophosphorylate tyrosine residues upon ligand binding (e.g., EGFR, Insulin Receptor).

SH2 Domain

A protein domain that binds to phosphorylated tyrosine residues.

SH3 Domain

A protein domain that binds to proline-rich sequences.

PH Domain

A protein domain that binds to phosphorylated lipids (like PIP3) in the membrane.

Hypoxia Inducible Factor (HIF-1alpha)

A transcription factor that is stable in low oxygen (hypoxia) and triggers angiogenesis genes (like VEGF).

Under normal oxygen levels, HIF-1alpha is degraded by the pathway.

Ubiquitin-proteasome

VHL (Von Hippel-Lindau) protein

An E3 ubiquitin ligase that targets HIF-1alpha for degradation when oxygen is present.

Bevacizumab (Avastin)

A monoclonal antibody that binds to VEGF, inhibiting angiogenesis (blood vessel growth) in cancer.

Central Dogma of Molecular Biology

The flow of genetic information: DNA -> RNA -> Protein.

Replication

The process of copying DNA to make more DNA.

Transcription

The process of synthesizing RNA from a DNA template.

Translation

The process of synthesizing proteins from an mRNA template.

Vicodin/OxyContin act as agonists for receptors.

Opioid

Statins (e.g., Lipitor) inhibit the enzyme .

HMG-CoA reductase

Ezetimibe

A drug that inhibits cholesterol transporters in the small intestine.

EML4-ALK

A fusion gene found in some non-small-cell lung cancers (NSCLC) caused by a chromosomal inversion; a target for specific kinase inhibitors.

Ozempic (Semaglutide) is an agonist for the receptor.

GLP-1 (Glucagon-like peptide-1)

Hit (in Drug Discovery)

A molecule that shows desired activity in a preliminary screen.

Lead (in Drug Discovery)

A "hit" molecule that has been optimized for better potency and selectivity.

ADME stands for…

Absorption, Distribution, Metabolism, Excretion (Pharmacokinetics).

Pharmacodynamics

The study of what the drug does to the body (mechanism of action).

Pharmacokinetics

The study of what the body does to the drug (ADME).

Phase I Clinical Trials

Tests mainly for safety and dosage in a small group of healthy volunteers.

Phase II Clinical Trials

Tests for efficacy and side effects in a larger group of patients with the disease.

Phase III Clinical Trials

Large-scale testing to confirm efficacy and monitor adverse reactions compared to standard treatments.

Nucleosome

The fundamental unit of chromatin, consisting of DNA wrapped around a histone octamer.

Histones are rich in and amino acids, giving them a positive charge.

Lysine

Histone Acetylation generally gene expression.

Activates (opens chromatin)

Histone Methylation

Can either activate or repress gene expression depending on the specific residue modified.

Topoisomerase I

An enzyme that cuts one strand of DNA to relieve supercoiling; does not require ATP.

Topoisomerase II

An enzyme that cuts both strands of DNA to relieve supercoiling; requires ATP.

Ciprofloxacin (Cipro) inhibits .

Bacterial Topoisomerase II (DNA Gyrase) and Topoisomerase IV

Doxorubicin

A chemotherapy drug that inhibits human Topoisomerase II, leading to DNA breaks and cell death.

Allopurinol mechanism of action

Inhibits Xanthine Oxidase, reducing uric acid production to treat Gout.

Purines

Nitrogenous bases with a double-ring structure: Adenine (A) and Guanine (G).

Pyrimidines

Nitrogenous bases with a single-ring structure: Cytosine (C), Thymine (T), Uracil (U).

Deamination of Cytosine produces .

Uracil

Transposons

"Jumping genes" or mobile genetic elements that can move within the genome.

Retrotransposons

Genetic elements that move via an RNA intermediate using reverse transcriptase (Copy and Paste).

DNA-only Transposons

Genetic elements that move directly as DNA (Cut and Paste) using transposase.

Alu elements are an example of .

Retrotransposons (SINEs) found in humans.

Synteny

The conservation of gene order on chromosomes between different species.

Ribosome

A complex of rRNA and proteins that serves as the site of protein synthesis.

The eukaryotic ribosome is S, composed of S and S subunits.

80S

The prokaryotic ribosome is S, composed of S and S subunits.

70S

A site (Ribosome)

Aminoacyl site; binds the incoming tRNA carrying an amino acid.

P site (Ribosome)

Peptidyl site; holds the tRNA carrying the growing polypeptide chain.

E site (Ribosome)

Exit site; where empty tRNAs leave the ribosome.

Direction of protein synthesis

N-terminus to C-terminus (mRNA is read 5' to 3').

Start Codon

AUG (Codes for Methionine).

Stop Codons

UAA, UAG, UGA (Do not code for amino acids).

Wobble Hypothesis

Explains why the third base of a codon can often mismatch with the tRNA anticodon, allowing fewer tRNAs to cover all codons.

Inosine

A modified base in tRNA that can pair with A, U, or C in the wobble position.

Aminoacyl-tRNA Synthetase

The enzyme responsible for attaching the correct amino acid to its corresponding tRNA (charging).

Shine-Dalgarno Sequence

A ribosome binding site in prokaryotic mRNA located upstream of the start codon.

Kozak Sequence

A sequence in eukaryotic mRNA that helps the ribosome identify the correct start codon (AUG).

eIF4E

A eukaryotic initiation factor that binds to the 5' cap of mRNA to recruit the ribosome.

Tetracycline Mechanism

Inhibits bacterial protein synthesis by blocking the A-site of the ribosome.

Puromycin Mechanism

Causes premature chain termination by mimicking aminoacyl-tRNA and entering the A-site.

Cycloheximide Mechanism

Inhibits eukaryotic translocation (elongation step).

Chloramphenicol Mechanism

Inhibits peptidyl transferase activity on the 50S subunit of bacteria.

Nonsense Mutation

A mutation that changes an amino acid codon into a stop codon, leading to a truncated protein.

Silent Mutation

A mutation that changes a nucleotide but does not change the amino acid encoded.

Missense Mutation

A mutation that changes a nucleotide and results in a different amino acid.

Frameshift Mutation

An insertion or deletion of nucleotides (not in multiples of 3) that alters the reading frame.

Paracrine Signaling

Signaling where cells release molecules that act on nearby target cells.

Endocrine Signaling

Signaling where cells release hormones into the bloodstream to act on distant target cells.

Autocrine Signaling

Signaling where a cell releases a molecule that binds to receptors on its own surface.

Juxtacrine (Contact-dependent) Signaling

Signaling that requires direct physical contact between the signaling and target cell.