DNA/RNA, Gene Expression, PGx, Protein Structure, & Signal Transduction

Vocabulary practice flashcards generated from lecture notes covering DNA/RNA synthesis, gene expression, pharmacogenomics, protein folding, enzyme kinetics, and cell receptor signaling pathways.

Purines

Nitrogen-containing double-ring bases found in nucleic acids, specifically Adenine (A) and Guanine (G) ('Pure As Gold').

Pyrimidines

Single-ring nitrogenous bases found in nucleic acids, including Cytosine (C), Thymine (T) in DNA, and Uracil (U) in RNA.

PRPP (Phosphoribosyl pyrophosphate)

An essential enzyme intermediate used in both de novo and salvage nucleotide synthesis pathways, found at decreased levels in post-mitotic cells and increased levels in proliferating cells.

Gout

An inflammatory joint condition caused by excessive breakdown of purine nucleotides leading to high levels of uric acid that accumulate as crystals in joints; treated with xanthine oxidase inhibitors like allopurinol and febuxostat.

DNA Polymerase III

The primary enzyme that synthesizes new DNA strands in the $5' \rightarrow 3'$ direction during DNA replication, continuously on the leading strand and discontinuously on the lagging strand.

Okazaki Fragments

Short, newly synthesized DNA fragments formed on the lagging template strand during DNA replication, which are joined together by DNA ligase.

Telomere

A region of repetitive nucleotide sequences located at each end of a chromosome that protects chromosome ends and is elongated in the $5' \rightarrow 3'$ direction by telomerase.

Base Excision Repair (BER)

A DNA repair pathway that fixes small, non-bulky single-base alterations (such as deamination or depurination) using DNA glycosylase to create an AP site before endonuclease, polymerase, and ligase seal the gap.

Nucleotide Excision Repair (NER)

A DNA repair mechanism that removes bulky lesions and structural distortions in the double helix, such as pyrimidine dimers caused by UV damage, using a multi-enzyme excision complex.

Homologous Recombination Repair

An accurate double-strand break repair mechanism that uses the sister chromatid as a template to conserve genetic material; defects in associated proteins like BRCA1/2 increase cancer risk.

Introns

Non-coding intervening sequences within a gene that are excised (snipped out) during pre-mRNA splicing before translation.

Exons

Expressed regions of a gene sequence that remain in mature mRNA after splicing and encode the final functional protein.

Promoter Region

A regulatory DNA sequence upstream of a gene's transcription start point (containing sequence motifs like the TATA box) where general transcription factors and RNA polymerase assemble.

Alternative Splicing

A process where pre-mRNA exons can be spliced together in different combinations, enabling a single gene to encode multiple distinct protein variants.

Essential Amino Acids

The 9 amino acids that cannot be synthesized by the human body and must be supplied through the diet (remembered by the mnemonic PVT TIM HaLL).

Branched Chain Amino Acids (BCAAs)

Isoleucine, leucine, and valine; essential amino acids containing branched side chains that bypass liver deamination, are shuttled via alanine in the Glucose-Alanine Cycle, and are readily available for muscle protein synthesis.

Transamination

The enzymatic transfer of an amino group from an amino acid to a carbon skeleton (alpha-keto acid), typically catalyzed by aminotransferases utilizing pyridoxal phosphate (PLP / Vitamin B6) as a cofactor.

Polysome (Polyribosome)

A series of multiple ribosomes attached to and simultaneously translating a single mRNA strand.

Euchromatin

Loosely packed, accessible chromatin that is transcriptionally active.

Heterochromatin

Densely packed chromatin structure that is transcriptionally inactive/repressed.

Single Nucleotide Polymorphism (SNP)

The most common type of genetic variation occurring when a single nucleotide base pair is substituted in at least 1% of the population.

Primary Protein Structure

The unique linear sequence of amino acids linked together by covalent peptide bonds.

Functional Domain

A modular section of a protein that can fold independently into a compact, stable structure and perform a specific function.

Heat Shock Proteins (Hsps)

Molecular chaperones (such as Hsp60 and Hsp70) that use ATP hydrolysis to bind hydrophobic regions on unfolded or misfolded proteins and assist in proper folding.

Proteasome

An ATP-dependent cylindrical protein complex that unfolds and degrades poly-ubiquitinated, damaged, or misfolded proteins into short peptide fragments.

Disulfide Bonds

Covalent sulfur-sulfur bonds formed between sulfhydryl groups of cysteine residues in the endoplasmic reticulum that stabilize tertiary and quaternary protein structures.

Kinase

An enzyme that catalyzes the addition of a phosphate group to a molecule or protein (phosphorylation).

Phosphatase

An enzyme that catalyzes the hydrolytic removal of a phosphate group from a molecule or protein (dephosphorylation).

Ubiquitination

The post-translational attachment of the small protein ubiquitin to a lysine residue of a target protein by ubiquitin ligase, tagging it for degradation or altered localization.

N-linked Glycosylation

The post-translational addition of sugar chains to the nitrogen atom of an asparagine (N) residue, accounting for approximately 90% of protein glycosylation.

Phase I Drug Metabolism

Biotransformation reactions (oxidative, hydrolytic, and reductive) primarily mediated by Cytochrome P450 enzymes in the liver that introduce or unmask a functional group on a drug.

Phase II Drug Metabolism

Conjugation biotransformation reactions that attach an endogenous molecule (e.g., acetyl group via N-acetyltransferases) to a drug or metabolite to facilitate excretion.

CYP3A4

The most abundant cytochrome P450 enzyme isoform in the liver and small intestine, responsible for metabolizing approximately 50% of clinically used drugs.

$$V_{max}$$

The maximal rate of an enzymatic reaction achieved when the enzyme is completely saturated with substrate.

$K_m$ (Michaelis Constant)

The substrate concentration at which the reaction velocity is half of $V_{max}$ ($\frac{1}{2} V_{max}$); serves as an inverse measure of enzyme affinity for its substrate.

Competitive Inhibitor

An inhibitor that competes directly with the substrate for binding at the enzyme's active site, resulting in an increased $K_m$ while leaving $V_{max}$ unchanged.

Non-competitive Inhibitor

An inhibitor that binds to an allosteric site on an enzyme (regardless of substrate binding), decreasing $V_{max}$ while leaving $K_m$ unchanged.

Uncompetitive Inhibitor

An inhibitor that binds exclusively to the enzyme-substrate ($E \times S$) complex, leading to a decrease in both $K_m$ and $V_{max}$.

Agonist

A ligand that possesses both receptor binding affinity and intrinsic cellular efficacy to activate a biological response.

Antagonist

A ligand that binds to a receptor with affinity but lacks intrinsic efficacy, thereby blocking or dampening the action of an agonist.

Down-regulation

A decrease in the net number or availability of cellular receptors caused by continuous or prolonged exposure to high levels of a ligand.

Gs Protein Signaling

A GPCR pathway where the activated alpha subunit stimulates adenylyl cyclase (AC), increasing cyclic AMP (cAMP) and activating Protein Kinase A (PKA).

Gi Protein Signaling

A GPCR pathway in which the activated alpha subunit inhibits adenylyl cyclase (AC), decreasing intracellular cAMP levels.

Gq Protein Signaling

A GPCR pathway where the alpha subunit activates phospholipase C (PLC), producing the second messengers $IP_3$, $DAG$, and increasing intracellular $Ca^{2+}$.

Arrestin

A regulatory protein that binds to GPCRs phosphorylated by GRKs, blocking further G protein interaction and triggering receptor-mediated endocytosis.

JAK/STAT Pathway

A signaling pathway activated by cytokines where receptor-associated Janus Kinases (JAKs) phosphorylate STAT proteins, causing STAT dimerization and nuclear translocation to induce gene transcription.