Biochem 501: Lecture 29: Biological Activity of Lipids
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Phosphoinositide cascade generates which second messengers
Diacylglycerol (DAG) and Inositol triphosphate (IP3)
DAG is an activator for?
Protein kinase C
IP3 causes release of?
Ca2+, 3rd messenger from intracellular stores
Steroid hormones produce effects how
directly binding and inducing transcription of genes
- 20 carbon unsaturated fatty acids derived from arachidonic acid
- -Arachidonic acid derived from linoleic acid, essential fatty acid
- Hormone-like biomodulator substances
Types of lipids
Storage, Membrane Lipids, Hormones, Fat Soluble Vitamins, Bile acids, Waxes, Pigments, Scents, ect.
Types of Storage Lipids
Neutral Fat: Triacylglycerols
Polar Lipids: Phospholipids, Glycolipids, Sphingolipids, Sterols
Types of Hormone Lipids
Types of Fat Soluble Lipids
A, D, K
PIP2 is cleaved into what
DG and IP3
Phosphoinositide cascade Step 1
- Hormone binds to receptor
- GDP bound to GP to become GTP
Phosphoinositide cascade Step 2
GTP bounded GP
moves to Phospholipase C (PLC) and activates it
Phosphoinositide cascade Step 3
- Active PLC cleaves PIP2 into IP3 and DG
Phosphoinositide cascade Step 4
binds to a specific receptor on ER, releasing Ca2+
Phosphoinositide cascade Step 5
- DG and Ca2+ activate PKC on plasma membrane
Phosphoinositide cascade Step 6
- PKC phosphorylates cellular proteins, producing the response to the hormones
Effects mediated by Phosphoinositide cascade
- Glycogenlysis in liver
- Histamine secretion of mast cells
- Serotonin release by blood platelets
- Smooth muscle contraction
- Visual transduction in invertebrate photo-receptors
- Insulin secretion by pancraetic islet cells
Steroid hormone formation
- -Affects protein and carbohydrate metabolism
- -Suppresses immune response, inflammation, and allergic responses.
- Regulates re-absorption of
- Na+, Cl-, HCO3- in the kidney
- -Male and female sex hormones.
- -Influence secondary sexual characteristics.
- -Regulate female reproductive cycle.
Steroid Hormone Receptors share?
Substantial sequence homology/functional domain substructure
Model for Steroid Receptor Action
- Serum binding protein carries hormone to plasma membrane
- Steroid enters cell, enters nucleus
- Steroid binds receptor on DNA, prompts transcription of mRNA
- Translation into new protein
Examples of specificity of steroid receptor binding in design of drugs
- Progesterone vrs. RU 486
- • RU 486 has similar structure as
- • It is used as an antagonist of
- progesterone in early termination of pregnancy
- Estrogen vs Tamoxifen
- • Tamoxifen has similar structure as estrogen
- • It competes with estrogen in binding to the estrogen receptor, but the tamoxifen receptor complex is inactive in gene regulation.
- The cancer cells that depend on estrogen for growth will be killed off. So tamoxifen is used in the treatment of breast cancer in humans.
Vitamin D is derived from what?
Vitamin D is a precursor to what
Hormone essential in calcium/phosphate metabolism
Sources of Vitamin D3
Formed in skin in reaction driven by UV light, in fish oils and as an additive in commercial milk
Active form of Vitamin D
Vitamin D deficiency leads to
Defective bone formation, aka rickets
Vitamin D formation pathway
Eicosanoid Formation Pathway
Functions of Eicosanoids
The inflamatory response
Regulation of pain and fever
Regulation of blood pressure
Induction of blood clotting
Control of reproductive functions
Regulation of the sleep-wake cycle
Short lived, target nearby cells
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