These notes have been compiled from past examination papers in Biochemical Endocrinology. Wishing you an insightful and productive study session. . 1. DDT (dich
These notes have been compiled from past examination papers in Biochemical Endocrinology. Wishing you an insightful and productive study session. . 1. DDT (dichlorophenyl trichloroethane) 2. Bisphenol A (BPA) 3. PCBs (polychlorinated biphenyl compounds) 4. Pesticides 5. Nonylphenols Adjuvant therapy – is when hormones are used with other therapies in cancer treatment to reduce side effects. - Example: Aromatase inhibitors + Tamoxifen the estrogen receptor antagonist used for treating breast cancer in menopausal women. - The goal of adjuvant therapy for breast cancer is to prevent the recurrence of the disease by eradicating micrometastatic disease. Features of Autacoids 1. Not released or stored in glands 2. Not circulated in blood 3. Have very short half-life ( t 1/2 ) 4. Are formed at the site of action 5. Produce localized action hCG is secreted by trophoblast cells of the developing placenta shortly after fertilization and implantation. It enters the maternal bloodstream and urine within 6–12 days post-conception. The test uses monoclonal antibodies specific to the β-subunit of hCG to ensure specificity (avoiding LH cross-reactivity). A sandwich ELISA or immunochromatographic method is used to detect hCG levels. A positive test line appears when hCG binds to the antibodies, confirming pregnancy. - Bone Turnover: Paget’s disease: Characterized by increased and disorganized bone remodeling . - Osteoporosis: Involves decreased bone mass and increased resorption , with normal remodeling pattern. - Bone Structure: Paget’s disease: Bones become enlarged, deformed, and structurally weak . - Osteoporosis: Bones are porous, thinned, and brittle due to loss of density. - Biochemical Markers: Paget’s disease: Often shows elevated alkaline phosphatase (ALP) due to increased osteoblastic activity. - Osteoporosis: Normal ALP , unless fracture or other condition is present. - Commonly Affected Sites: Paget’s disease: Affects skull, pelvis, femur, and spine . - Osteoporosis: Common in vertebrae, hip (femoral neck), and wrist . A. Biosynthesis of Catecholamines: - Tyrosine (from phenylalanine) is the precursor. - Step 1: Tyrosine → DOPA via tyrosine hydroxylase . - Step 2: DOPA → Dopamine via DOPA decarboxylase . - Step 3: Dopamine → Norepinephrine via dopamine β-hydroxylase . - Step 4: Norepinephrine → Epinephrine via phenylethanolamine N-methyltransferase (in adrenal medulla). - Stored in vesicles, released upon stimulation. B. Role in Human Behavior: - Dopamine: Reward, motivation, mood regulation, addiction, motor control (Parkinson’s, schizophrenia). - Norepinephrine: Alertness, attention, arousal, stress response. - Epinephrine: Fight-or-flight, enhances fear, anxiety, and performance. - Clinical implications: ADHD, mood disorders, substance abuse. - GABA-A (ionotropic): Ligand-gated chloride channels → hyperpolarization → inhibition. Targeted by benzodiazepines, barbiturates, alcohol . - GABA-B (metabotropic): G-protein coupled → opens K⁺ channels and inhibits Ca²⁺ channels. Affected by baclofen . - Both reduce neuronal excitability, contributing to inhibitory neurotransmission. Importance: - Produces cortisol , aldosterone , androgens (cortex), and epinephrine , norepinephrine (medulla). - Regulates stress response, blood pressure, metabolism, and electrolyte balance. Disorders: - Cushing’s Syndrome: Excess cortisol (hypertension, obesity). - Addison’s Disease: Cortisol/aldosterone deficiency (fatigue, hypotension). - Congenital Adrenal Hyperplasia: Enzyme defects → androgen excess. - Pheochromocytoma: Catecholamine-secreting tumor (sweating, palpitations). Hypothalamic Hormones: - TRH : Stimulates TSH and prolactin. - CRH : Stimulates ACTH. - GnRH : Stimulates LH and FSH. - GHRH : Stimulates GH. - Somatostatin : Inhibits GH and TSH. - Dopamine : Inhibits prolactin. Pituitary Hormones: - Anterior Pituitary: TSH : Thyroid stimulation. - ACTH : Stimulates adrenal cortex. - GH : Growth, metabolism. - PRL : Lactation. - FSH/LH : Reproduction. - Posterior Pituitary: ADH : Water retention. - Oxytocin : Uterine contractions, milk ejection. Clinical Relevance: - Disorders: Acromegaly, hypopituitarism, SIADH, diabetes insipidus, prolactinoma. - Inhibits Desire: High serotonin levels can reduce sexual desire and arousal. - Sexual Dysfunction: Low serotonin is linked to issues like premature ejaculation and erectile dysfunction. - Orgasm Regulation: Serotonin can delay orgasm and influence sexual response. - SSRIs: Antidepressants (SSRIs) affect serotonin, often causing sexual side effects. - Sensory Neurons: Transmit sensory information to the CNS (e.g., pain, touch). - Motor Neurons: Carry signals from the CNS to muscles/glands (e.g., skeletal muscle). - Interneurons: Connect sensory and motor neurons within the CNS, processing information. - Barbiturates: Increase GABA’s effect by prolonging chloride channel opening; potent anxiolytic/sedative, but risk of overdose. - Benzodiazepines: Increase GABA’s effect by enhancing chloride channel opening frequency; safer than barbiturates, but long-term use can cause dependence. - Mate Attraction: Signals reproductive status. - Territorial Marking: Marks boundaries. - Social Communication: Facilitates group cohesion (e.g., alarm signals). - Maternal Behavior: Influences maternal care. - Uterine Contractions: Facilitates childbirth. - Milk Ejection: Stimulates milk release during breastfeeding. - Excitatory: Glutamate – Excites neurons. - Inhibitory: GABA – Inhibits neuronal activity. - Modulatory: Dopamine – Modulates mood and movement. - Peptide: Endorphins – Natural pain relief. - Allelopathic Chemicals: Inhibit the growth of other organisms. - Kairomones: Beneficial to the receiver, e.g., predator locates prey. - Allomones: Beneficial to the emitter, e.g., deterrent chemicals. - Hypothyroidism: Low hormone levels; symptoms include fatigue and weight gain. - Hyperthyroidism: High hormone levels; symptoms include weight loss and tremors. - Goiter: Enlarged thyroid, often due to iodine deficiency. - Thyroid Cancer: Malignant growth in thyroid cells. - Thyroid Storm: Severe hyperthyroidism with life-threatening symptoms. - Hormone Binding to GPCR: Hormone binds to the extracellular domain of the GPCR (7-helix receptor). - Conformational change in the receptor activates the G-protein on the cytosolic side. - GDP-GTP Exchange: The nucleotide-binding site on Ga becomes accessible to GTP. - Ga releases GDP and binds GTP, activating the G-protein. - Dissociation of Ga-GTP: Ga-GTP dissociates from the inhibitory bγ complex. - Ga-GTP can now bind to and activate Adenylyl Cyclase (AC) . - Activation of Adenylyl Cyclase: Adenylyl Cyclase is activated by Ga-GTP , catalyzing the synthesis of cAMP from ATP. - Activation of Protein Kinase A (PKA): cAMP activates Protein Kinase A (PKA) . - PKA transfers phosphate from ATP to cellular proteins, altering their activity. - GTP Hydrolysis by Ga (GTPase Activity): Ga hydrolyzes GTP to GDP and Pi . - This causes Ga to rebind to the bγ complex, turning off the signal. - Adenylyl Cyclase is no longer activated. - Hydrolysis of cAMP (Phosphodiesterases): Phosphodiesterases hydrolyze cAMP into AMP , reducing signal strength. - Receptor Desensitization: Activated receptors may be phosphorylated by G-protein Receptor Kinase (GRK). - Phosphorylated receptors may bind β-arrestin , which promotes receptor removal or internalization. - β-arrestin can also recruit phosphodiesterase , bringing it closer to cAMP production to enhance signal turnoff. - Dephosphorylation of Proteins (Protein Phosphatase): Protein Phosphatase removes phosphates from proteins previously phosphorylated by PKA , reversing the cellular effects. - Toxin Production: Both Cholera toxin and Pertussis toxin involve the process of ADP-ribosylation . - Cholera Toxin Mechanism: Cholera toxin catalyzes ADP-ribosylation of Gαs (stimulatory G-protein). - ADP-ribose is transferred from NAD+ to an arginine residue at the GTPase active site