University:
Kentucky State University
Course:
CHE 315 | Biochemistry
Academic year:

2024
Views:

482

Pages:

36
Author:

Tyshawn Shaffer

Receptors Functions and Signal Transduction- L4- L5 107 ▪ Receptors superfamilies: ▪Ionotropic receptors (ligand-gated channels) ▪Metabotropic receptors (G protein-coupled receptors) ▪Tyrosine Kinase Almost all neurotransmitters discovered so far have more than one kind of receptor -- called receptor subtypes. 108 Blood capillary 1 Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Water-soluble hormone Adenylate cyclase Receptor Second messenger G protein ATP cAMP 2 Activated adenylate cyclase converts ATP to cAMP Protein kinases 6 Phosphodiesterase inactivates cAMP 3 cAMP serves as a second messenger to activate protein kinases Activated protein kinases 4 Activated protein Protein kinases phosphorylate cellular proteins ATP ADP Water-soluble Hormones Protein— P 5 Millions of phosphorylated proteins cause reactions that produce physiological responses 109 Target cell 110 Cyclic Monophasphate (cAMP) Second Messenger Mechanism 111 Cell Membrane Phospholipid Second Messenger System 112 Epinephrine Can Act Through Two 2nd Messenger Systems 113 Free hormone Blood capillary 1 Lipid-soluble Transport protein hormone diffuses into cell 2 Activated Nucleus Receptor receptor-hormone complex alters gene expression DNA Cytosol mRNA 3 Newly formed mRNA directs synthesis of specific proteins on ribosomes Ribosome New protein 4 New proteins alter Lipid-soluble Hormones cell's activity Target cell Hormones That Bind to Nuclear Receptor Proteins   Lipophilic steroid and thyroid hormones are attached to plasma carrier proteins.  Hormones dissociate from carrier proteins to pass through lipid component of the target plasma membrane. Receptors for the lipophilic hormones are known as nuclear hormone receptors. Nuclear Hormone Receptors     Steroid receptors are located in cytoplasm and in the nucleus. Function within cell to activate genetic transcription.  Messenger RNA directs synthesis of specific enzyme proteins that change metabolism. Each nuclear hormone receptor has 2 regions:  A ligand (hormone)-binding domain.  DNA-binding domain. Receptor must be activated by binding to hormone before binding to specific region of DNA called HRE (hormone responsive element).  Located adjacent to gene that will be transcribed. 116 Mechanisms of Steroid Hormone Action      Cytoplasmic receptor binds to steroid hormone. Translocates to nucleus. DNA-binding domain binds to specific HRE of the DNA. Dimerization occurs.  Process of 2 receptor units coming together at the 2 half-sites. Stimulates transcription of particular genes. 117 Mechanism of Thyroid Hormone Action   T4 passes into cytoplasm and is converted to T3. Receptor proteins located in nucleus.  T3 binds to ligand-binding domain.  Other half-site is vitamin A derivative (9-cis-retinoic) acid.   DNA-binding domain can then bind to the halfsite of the HRE. Two partners can bind to the DNA to activate HRE.  Stimulate transcription of genes. Steroid & Thyroid Hormones - Mechanism of Action 119 Actions of Thyroid Hormones 120 Determinants of Free Hormone Receptor Binding Carrier-bound hormone Endocrine cell Free Hormone Hormone receptor Hormone degradation Biological effects 121 Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with Degree of Protein Binding Hormone Protein Plasma half-life binding (%) Metabolic clearance (ml/minute) Thyroid Thyroxine Triiodothyronine 99.97 99.7 6 days 1 day Steroids Cortisol Testosterone Aldosterone 94 89 15 100 min 85 min 25 min 140 860 1100 Proteins Thyrotropin Insulin Antidiuretic hormone little little little 50 min 8 min 8 min 50 800 600 0.7 18 MCR = (mg/minute removed) / (mg/ml of plasma) = ml cleared/minute 122 Circulating Transport Proteins Transport Protein Principle Hormone Transported Specific Cortisol, aldosterone Corticosteroid binding globulin (CBG, transcortin) Thyroxine binding globulin (TBG) Thyroxine, triiodothyronine Testosterone, estrogen Sex hormone-binding globulin (SHBG) Nonspecific Albumin Transthyretin (prealbumin) Most steroids, thyroxine, triiodothyronine Thyroxine, some steroids 123 Feedback Mechanisms Positive Feedback Negative Feedback + + Endocrine cell _ Target cell Endocrine cell Target cell + Biological effects Biological effects 124 Steroid & Thyroid Hormones - Receptors 125 126 Tyrosine Kinase 127 Tyrosine Kinase Receptors: 128 129 Tyrosine Kinase    Insulin receptor consists of 2 units that dimerize when they bind with insulin.  Insulin binds to ligand–binding site on plasma membrane, activating enzymatic site in the cytoplasm. Autophosphorylation occurs, increasing tyrosine kinase activity. Activates signaling molecules.  Stimulate glycogen, fat and protein synthesis.  Stimulate insertion of GLUT-4 carrier proteins. 130 Tyrosine Kinase (continued) 131 The Insulin Receptor & Mechanisms of Insulin Action 132 133 Insulin Action on Cells: 134 135 136 137 138 139 Signaling molecule (hormones) Receptor of target cell Signal transduction Intracellular molecule (second messengers) biological effect 140 Third messengers: Third messengers are the molecules which transmit message from outside to inside of nucleous or from inside to outside of nucleous, also called DNA binding protein. 141 Effect by membrane receptors Extracellular molecules Effect by intracellular receptors Signal molecules Intracellular molecules Proteins and peptides: Hormones, cytokines Amino acid derivatives: Catecholamines Fatty acid derivatives: Prostaglandins Steroid hormones, Thyroxine, VD3 cAMP, cGMP, IP3, DG, Ca2+ 142

Receptors Functions and Signal Transduction L4-L5

Related Documents

Recommended Documents

Description

Related Documents

Free up your schedule!

Take 5 seconds to unlock