Short Notes Topics

G-Proteins

✅ Definition in one line for exams:
“G-proteins are guanine nucleotide-binding proteins that act as molecular switches in signal transduction, coupling receptors to intracellular effectors.”

A G-protein (Guanine nucleotide-binding protein) is a molecular switch inside cells that helps transmit signals from cell surface receptors to intracellular targets.

• They are called G-proteins because they bind guanosine triphosphate (GTP) and guanosine diphosphate (GDP).

• G-proteins are involved in signal transduction — converting an extracellular signal (like a hormone, neurotransmitter, or light) into a cellular response.

🔎 Key Features

1. Location → Found on the inner surface of the plasma membrane, linked to G-protein-coupled receptors (GPCRs).

2. Subunits → Usually exist as a heterotrimer with α, β, and γ subunits.

o α-subunit binds GDP/GTP and has GTPase activity.

o βγ complex also participates in signaling.

3. Switch Mechanism:

o Inactive state → bound to GDP.

o Active state → when the receptor stimulates, GDP is replaced by GTP → the G-protein activates downstream effectors.

o Later, α-subunit hydrolyzes GTP → GDP (turns itself off).

⚙️ Functions

• Activate or inhibit enzymes like adenylate cyclase or phospholipase C.

• Regulate ion channels.

• Control production of second messengers (e.g., cAMP, IP₃, DAG).

Clinical Significance

• Many hormones (e.g., adrenaline, glucagon, ACTH) act via G-proteins.

• Diseases can result from G-protein malfunction (e.g., cholera toxin locks G-protein in active state → ↑cAMP → diarrhea).

✅ Definition (short form):
“Cytochrome P450 is a superfamily of heme-containing monooxygenase enzymes that catalyze drug metabolism and biosynthesis of steroids, located mainly in the liver.”

Cytochrome P450 (CYP450)

Cytochrome P450 (CYP450) is a large family of heme-containing enzymes that act as monooxygenases.

Location: They are mainly found in the smooth endoplasmic reticulum and mitochondria of cells.

Why "P450": They are named “P450” because they absorb light at 450 nm when bound to carbon monoxide.

🔎Key Functions

1. Drug Metabolism (Phase I reactions)

o Oxidation, reduction, and hydroxylation of drugs.

o Converts lipid-soluble drugs into more water-soluble metabolites (often preparing them for Phase II conjugation).

2. Endogenous Metabolism

o Steroid hormone synthesis (cortisol, estrogen, testosterone).

o Vitamin D metabolism.

o Metabolism of fatty acids, bile acids, and prostaglandins.

Reaction (General)

RH+O2+NADPH+H+→ROH+H2O+NADP+RH + O_2 + NADPH + H^+ → ROH + H_2O + NADP^+

RH = substrate (drug or compound)

Adds an -OH group (hydroxylation)

📍 Location

• Liver (major site) → drug detoxification.

• Also in the intestine, lungs, kidneys, and adrenal glands.

Clinical Relevance

• Drug interactions:

  • Some drugs induce CYP450 → increase metabolism of other drugs (e.g., rifampicin, phenytoin).

  • Some drugs inhibit CYP450 → slow metabolism, increase toxicity risk (e.g., erythromycin, ketoconazole).

• Genetic polymorphisms:

  • Different CYP450 isoenzymes vary among individuals, → explains why some patients metabolize drugs faster/slower.

• Toxins/Carcinogens:

  • Can activate pro-carcinogens (e.g., benzopyrene from cigarette smoke).