BMS2021 Lecture Notes - Lecture 6: Surface 2, Exocytosis, Thyroglobulin

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Week 3. Biochemistry in human function
CELL COMMUNICATION AND SIGNAL TRANSDUCTION & SYNTHESIS,
DEGRADATION AND ACTIONS OF HORMONES
• Communication is required for:
1. Regulation of development and organisation into tissues
2. Control of growth, death and division
3. Coordination of the diverse cellular activities
• 2 parallel systems for regulation and integration of bodily functions:
1. Endocrine system: acts via hormones
endocrine gland -> hormone -> signal for release -> transport to target (water soluble, go
through blood) -> binding to receptor (on or in cell) -> modification of metabolism/cell
growth/function -> switch off secretion -> degradation/inactivation of hormone (mostly in
liver, little pass through hormones)
2. Nervous system: acts via neurotransmitters (physical contact)
• Cells communicate in 3 ways:
1. Secrete chemicals that signal cells
2. Display plasma membrane bound signalling molecules that influence other cells which make
direct physical contact
3. For gap juctios that directly joi cytoplas’s of interacting cells (important in embryonic
development)
Autocrine
Hormone operates on same cell that released it
Paracrine
Message goes to a limited area in vicinity i.e. message is not stable
Endocrine
Messenger is secreted with travels to target cell at a distance (hormonal system)
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• Major endocrine glands:
o Hypothalamus
o Pituitary
o Thyroid
o Adrenals
o Pancreas
o Testes
• Hormones regulate:
o Rate of transport of molecules by altering permeability of cell membranes
o Synthesis of nucleic acids and proteins
o Metabolism of carbohydrates, fats and proteins
• Hormones can be divided into three main classes:
Polypeptide/protein
Ie. Insulin
o Stored in secretory vesicles (up to 1 day)
o Many stored as prohormones (need to be activated by enzyme and
can yield more than one hormone)
o Released by exocytosis of secretory granules (most are water soluble)
o Secretion is regulated by other hormones, metabolites, CNS
o Circulate free in blood (lifetime of mins)
o Receptors at cell surface
o Inactivation: proteolysis/uptake in cells
o Eg. Leptin
-made by adipocytes
-acts on brain and hypothalamus
-inhibits food intake
-effects on respiratory development, liver and skeletal muscles
-mutations -> obesity, hyperphagia
Amine hormones
o Tyrosine derived
o Stored for several days
o Ie. Epinephrine/norepinephrine (stress hormones) -> adrenal medulla
(and CNS)
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-stored for several days
-secreted in response to signals from CNS (exocytosis of vesicles)
-receptors at cell surface
-free in blood (lifetime of seconds)
-inactivation: methylation/conjugation
o Thyroxine (T4)/Triiodothyronine (T3) (metabolism and development
of brain -> thyroid gland
-released by proteolytic cleavage (proteolysis of thyroglobulin)
-T4 increases rate of cell metabolism
-T3 biologically active than T4
-stored for several weeks
-transport: bound to plasma proteins (TGB, transthyretin and
albumin)
-lifetime of days in blood
-receptors are nuclear (within cell)
-inactivation: conjugation/deamination
Steroid hormones
Ie. Estrogen/testosterone
o Synthesised from cholesterol (adrenal cortex, gonadal steroids)
o Controlled by hypothalamus/pituitary
o Synthesised in adrenal cortex, ovaries and testis
o Very specific
o Nuclear receptors
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Document Summary

Hormone operates on same cell that released it. Paracrine message goes to a limited area in vicinity i. e. message is not stable. Effects on respiratory development, liver and skeletal muscles. Mutations -> obesity, hyperphagia: tyrosine derived, stored for several days. Epinephrine/norepinephrine (stress hormones) -> adrenal medulla (and cns) Secreted in response to signals from cns (exocytosis of vesicles) Inactivation: methylation/conjugation: thyroxine (t4)/triiodothyronine (t3) (metabolism and development of brain -> thyroid gland. Transport: bound to plasma proteins (tgb, transthyretin and albumin) Estrogen/testosterone: synthesised from cholesterol (adrenal cortex, gonadal steroids, controlled by hypothalamus/pituitary, synthesised in adrenal cortex, ovaries and testis, very specific, nuclear receptors. Steroid hormones: aldosterone: sodium uptake, meds -> regulate blood pressure, differ in side chains, ~ 48 receptors. ~5 orphan receptors (no known ligand: vitamin a, vitamin d, modification and excretion: To be more soluble: hydroxylated/hydrogenated, sulphated, sugars added, glucuronide conjugation) Usually bound to transporters (albumin -> transports most steroid hormones) Modified forms lost in urine: diseases: cushings disease.

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