Principles of metabolism regulation

1
Principles of metabolism regulation

• Molecular mechanisms of hormonal signal
  transduction

2
Ways of cell communicationAutocrine way of
signal trunsduction
Secretory cell is also a target for its own
hormone

• Secretory cell secretes a hormone into
  extracellular medium. A hormone binds to the same
  cell inducing physiological response.

3
Ways of cell communicationParacrine way of
signal trunsduction

• There are several types of cells in an
  organ/tissue.
• Secretory cells release first messenger (hormone)
  into extracellular medium. First messenger can
  reach an adjacent cell and combine with its
  receptors

Secretory cell
4
Ways of cell communicationEndocine way of signal
trunsduction

• A cell secretes a chemical compound into blood.
  Blood transports this compound into tissues,
  where a compound combines with cells inducing
  physiological response. A chemical compound
  secreted into blood is first-messenger. In
  physiological terms, it is a hormone.
• An organ (tissue) upon which a hormone acts is
  considered as a target-organ(tissue).
• Cells of target organ/tissue contain receptors
  specific in regard to a hormone. Receptors
  proteins.

5
Neuroendocrine system and its ranking

• Hypothalamic-hypophyseal axis is controled by
  neural imputs from CNS.
• Hypothalamic hormones act on cells of
  adenohypophysis. Cells of adenohypophysis are
  considered as first rank target cells.
• Hormones of adenohypophysis act on cells of
  peripheral endocrine glands. The cells of
  peripheral endocrine glands are second rank
  target cells.
• Hormones of peripheral endocrine glands act on
  cells of various tissues. These cells are
  ultimate targets or third rank of target cells.

6
Feedback inhibition in neuroendocrine system
7
Hypothetical model of target cell
8
Functional classification of plasma membrane
reseptors

• Receptors linked to adenylate cyclase system.
  Cyclic adenosine monophosphate (cAMP) is second
  messenger.
• Receptors linked to phospholipase C system.
  Inositol triphosphate (IP3), diacylglycerol (DAG)
  ir Ca2 are second messengers.
• Receptors with enzymatic properties receptory
  tyrosine kinase and receptory guanylate cyclase.

9
Hormone action via plasma membrane receptors

• These receptors are characteristic to all
  hormones soluble in water.
• The main steps of action formation of H-R
  complex synthesis of second messenger (second
  messenger is a regulatory molecule immediately
  produced in a target cell in response to
  hormone) alterations of activities of
  intracellular enzymes physiological response.

10
Hormone
Receptor
Receptor
Plasma membrane
Functioning of receptors linked to adenylate
cyclase
Adenilatciklaz
e
Adenylate cyclase
G-protein
-
b
a
ltymas
Proteinkinaze A
Proteinkinase A
Neaktyvi
Inactive
Proteinkinase A
i
active
Phosphorylase kinase Inactive, dephosphorylated
Phosphorylase kinase Active, phosphorylated
Glycogenphosphorylase b inactive dephosphorylated
Glycogenphosphorylase a ative
Glycogen( n)
cAMP-mediated breakdown of glycogen
(Glucose-1-phosphate) n
11
Synthesis of cAMP
Adenylate cyclase
12
cAMP decomposition
Phosphodiesterase
H2O
Inhibited by alkaloids, e.g. caffeine
13
Hormones acting via cAMP

• Glucagon
• Adrenalin (activation ß-adrenoreceptors results
  in cAMP increasing, but a2 in increasing)
• Calcitonin
• Vasopressin (ADH, antidiuretic hormone) if
  interacts with V2-type receptors in cells of
  distal tubules of kidney.

14
G-proteins as mediators of R-enzyme interaction
H
H
Adenylate cyclase
15
Transduction of hormonal signal through
phospholipase C system
16
Hormones acting via phospholipase C system

• Adrenalin/noradrenalin (via a1-adrenoreceptors)
• Vasopressin (ADH) via V1receptors (in smooth
  muscles cells of blood vessels)

17
Enzymatic receptors. Hormones acting via
enzymatic receptors

• Insulin
• Somatotropin/ growth hormone (GH)
• Insulin-like growth factors
• Cytokins
• Natriuretic peptides

18
Receptors with tyrosine kinase activity
receptory tyrosine kinase
19
Receptors with guanylate cyclase activity
20
Synthesis of cGMP by guanylate cyclase
GTP
cGMP
21
Action of hormones via intracellular receptors

• Intracellular receptors bind only water insoluble
  hormones (lipophilic ones steroid-, thyroid
  hormones and retinoic acid).
• True second messengers are not produced.
• Receptors are located in cytoplasm and nucleus
  of target cells.

22
Hormone action through intracellular receptors
Baltymas
23
Hsp and receptor complex
24
Structure of receptor specific to lipophilic
hormone