LECTURE 4. Hormones and mechanisms of their influence on
metabolic processes
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Faculty of Veterinary Medicine, lilkalachnyuk@gmail.com
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Thematic Module 4. Regulatory effects of inorganic and organic
substances on the metabolism
LECTURE 4
Hormones and mechanisms of their
influence on metabolic processes
prolactin
Hormones as Regulators of metabolism
Common characteristics of hormones
and
their
molecular
structure,
biosynthesis, and metabolism.
Mechanisms of hormonal influence on
metabolic processes
Principles of hormone action
Depending on the type of hormone, hormone signals are transmitted to the
target cells in different ways.
Polar (hydrophilic) hormones act on the external cell membrane, while
apolar (lipophilic) hormones penetrate the cell and act in the cell nucleus.
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Hormones are chemicals released by a cell or a gland in
one part of the body which send out messages that affect
cells in other parts of the organism.
Only a small amount of hormone is required to alter cell
metabolism. In essence, it is a chemical messenger that
transports a signal from one cell to another.
All multi-cellular organisms produce hormones; plant
hormones are also called phytohormones.
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Epinephrine is more of a hormone than a neurotransmitter: the main place of
synthesis is the adrenal medulla.
Regulation of secretion of epinephrine is carried out under effect of nervous
system. The level of epinephrine increases dramatically under the influence of
stress factors (fear, physical, mental overload).
Metabolic regulation is carried out under the influence of changes in the
concentration of glucose in the blood, in particular, hypoglycemia stimulates the
secretion of epinephrine. The mechanism of action of epinephrine is bonded to
“adenylate cyclase effect” (see above, slide 7) and its interaction with betaadrenergic receptors of the plasma membrane and the launch of a cascade of
reactions in the cell leading to the decomposition of glycogen and fats (Earl
Sutherland, the Nobel Prize).
Norepinephrine is more of a neurotransmitter than a hormone: the main site of
synthesis – neurons of central nerve system (CNS).
Biological effects of epinephrine (norepinephrine):
1) contraction of smooth muscle of vessels and increase of arterial pressure,
increase of frequency and force of heart contractions, contraction of smooth
muscles of other organs;
2) Mobilization of glucose and hyperglycemia (stimulates decomposition and
inhibits the synthesis of glycogen);
3) Mobilization of fats (stimulates the decomposition of triglycerides, increases
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the content of fatty acids in the blood);
Principles of hormone action – A [4]
The group of hydrophilic
hormones
consists
of
hormones derived from
amino acids, as well as
peptide
hormones
and
proteohormones.
Their
receptors are located in the
plasma membrane. Binding
of the hormone to this type
of receptor triggers a signal
that is transmitted to the
interior of the cell, where it
controls the processes that
allow the hormone signal to
take
effect
(signal
transduction).
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Principles of hormone action – B [4]
Lipophilic hormones,
which
include
the
steroid
hormones,
thyroxine, and retinoic
acid, bind to a specific
receptor protein inside
their target cells. The
complex formed by the
hormone
and
the
receptor
then
influences transcription
of specific genes in the
cell nucleus
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[4]
B
Hormonal
regulation of
glucose
metabolism
in the liver
A
A
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Regulation of lipolysis
Hormones (that affect lipolytic processes) are divided into
2 groups:
1. Hormones of direct action (adrenaline, glucagon,
somatotropin, insulin)
2. Hormones of mediated action (thyroid hormones,
glucocorticoids, sex hormones, leptin)
Epinephrine,
glucagon,
somatotropin,
sex
hormones,
thyroxin
and
triiodothyronine,
leptin
stimulate
lipolysis
in
adipocytes,
and
insulin
is
suppressed.
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Classification of hormones
I. According to chemical nature
II. According to place of synthesis
III. According to biological effect (true
hormones and hormone like substances)
IV. According to nature of action : starting
hormones and hormones-performers (or
hormones-players)
V. According to mechanism of effect, there
are 2 types: 1) action on receptor of
external membrane of target cell; 2)
action on receptors inside of cell
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I – according to chemical nature, hormones are
➢protein-peptide nature hormones: protein (insulin), peptides
(oxytocine);
➢derivatives of amino acids (thyroxine);
➢lipid-hormones: steroids (androsterone), eicosanoids;
➢derivatives of phenols (epinephrine or adrenaline)
II – according to place of synthesis, hormones are divided
into:
✓Hormones central endocrine structures
✓Hormones peripheral endocrine structures
✓Hormones of the mixed function
✓Hormones diffuse endocrine system
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III – according to biological effect, hormones are:
true hormones
hormone like substances (hormoides)
According to biological effect, hormones are:
true hormones:
1) hormones of the hypothalamus (8 liberin or releasing factors
and 3 statins, such as thyrotropin-releasing hormone (TRH),
also called thyrotropin-releasing factor (TRF), thyroliberin or
protirelin, gonadotropin-releasing hormone (GnRH), also
known as luteinizing-hormone-releasing hormone (LHRH) and
luliberin, is a tropic peptide hormone responsible for the
release of follicle-stimulating hormone (FSH) and luteinizing
hormone (LH) from the anterior pituitary, and somatostatin),
pituitary
hormones
(anterior
pituitary
hormones
or
‘adenohypophiz’: somatotropin, prolactin, folitropin, lutropin,
corticotropin, thyrotropin; pituitary hormones secondary:
melanotropin; posterior pituitary hormones secondary or
‘neurohypophiz’: vasopressin and oxytocin), pineal gland
hormone (melanotonin);
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2) thyroid hormones (such as triiodothyronine, calcitocin
(«гіпокальціємiйний гормон кальцитоцин»);
3) parathyroid gland hormones or parthyroid hormones
(parathormone or parathyrin);
4) hormones of the adrenal gland (glucocorticoids –
corticosteron,
hydrocorticosteron,
cortisone,
mineralocorticoids – aldosterone, dezoxycorticosteron;
androgens androstenedione, testosterone, estrogen –
‘estrogen ekvilenin’);
5) hormones of the adrenal hormones brain (catecholamines –
adrenaline, noradrenaline);
6) hormones islet apparatus of the pancreas (insulin, glucagon,
‘lipokayin’, vahotonin;
7) hormones of male and female gonads (androgens:
androsterone,
dehidroandrosteron,
testosterone,
metyltestosteron; estrogens – estrone, estradiol, estratriol;
gestagens – pregnan, progesterone, relaxin, androgens,
hormones placenta – chorionic gonadotropin).
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hormone like substances (hormonoids):
✓prostaglandins;
✓hormonoids gastrointestinal tract - gastrin, secretin,
pancreozymin, cholecystokinin;
✓other
hormonoids
angiotensin,
kinin;
parahormone;
✓tissue hormone;
✓histo-hormone (histamine);
✓local action hormones;
✓neurohormones
histamine,
serotonin,
acetylcholine.
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IV – according to nature
of
action
:
starting
hormones and hormonesperformers (or hormonesplayers)
Starting hormone
are hypothalamic neurohormones that stimulate the
activities of the endocrine
glands.
Hormonesperformers are influenced
on the main metabolic
reactions of the organism
that ensure its growth,
development, production,
adaptation,
reproduction,
various functional activities,
etc.
Koolman,
Color Atlas of
Biochemistry,
2nd edition ©
2005 Thieme
14
V – according to mechanism of effect, there are 2 types: 1) action
on receptor of external membrane of target cell; 2) action on
receptors inside of cell
1) effect on the outer membrane receptor target cells (protein and
peptide hormones, catecholamine and horminoids)
Hormone acts on the outer membrane receptor target cells, in which
more is curried out → neurotransmitters (cAMP, cGMP,
prostaglandin, Ca2+) → enzymes’ systems of target cells →
metabolism in target cells
2) action on receptors within target cells (steroids, part of thyroid
hormones)
Hormone → inside target cells → interacts with molecules
glycoprotein receptors localized in the cytosol, mitochondria and
nuclear membrane → impact on the entire cellular metabolism,
primarily on the processes of transcription in target cells
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Insulin is composed of two peptide chains
referred to as the A chain and B chain.
A and B chains are linked together by two disulfide
bonds, and an additional disulfide is formed within the A
chain.
In most species, the A chain consists of 21 amino
acids and the B chain of 30 amino acids
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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Insulin biosynthesis [4]
Insulin is produced by the B cells of the islets of Langerhans in the pancreas. As is
usualwith secretory proteins, the hormone’s precursor (preproinsulin) carries a
signal peptide that directs the peptide chain to the interior of the endoplasmic
reticulum. Proinsulin is produced in the ER by cleavage of the signal peptide and
formation of disulfide bonds. Proinsulin passes to the Golgi apparatus, where it is
packed into vesicles—the β-granules. After cleavage of the C peptide, mature
insulin is formed in the β-granules and is stored in the form of zinc-containing
hexamers until secretion.
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Insulin
undergoes
extensive
posttranslational
modification along
the
production
pathway.
Production
and
secretion are largely
independent;
prepared insulin is
stored
awaiting
secretion.
Both C-peptide and
mature insulin are
biologically
active.
Cell components and
proteins in this image
are not to scale.
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Effect of insulin on glucose uptake and metabolism.
Insulin binds to its receptor (1), which starts many protein
activation cascades (2). These include translocation of
Glut-4 transporter to the plasma membrane and influx of
glucose (3), glycogen synthesis (4), glycolysis (5) and fatty
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acid synthesis (6).
Effects of insulin
deficiency [4]
Diabetes mellitus is a very
common metabolic disease
that is caused by absolute or
relative insulin deficiency.
The lack of this peptide
hormone
mainly
affects
carbohydrate
and
lipid
metabolism.
Diabetes
mellitus occurs in two forms.
In type 1 diabetes (insulindependent diabetes mellitus,
IDDM), the insulin-forming
cells are destroyed in young
individuals
by
an
autoimmune reaction.
The less severe type 2
diabetes
(noninsulindependent diabetes mellitus,
NIDDM) usually has its first
onset in elderly individuals.
The causes have not yet
been explained in detail in
this type.
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Carbohydrate
metabolism
regulation
Koolman, Color
Atlas of
Biochemistry, 2nd
edition © 2005
Thieme
21
Structure Glucagon is a 29amino acid polypeptide. Its
primary structure in humans is:
NH2-His-Ser-Gln-Gly-Thr-PheThr-Ser-Asp-Tyr-Ser-Lys-TyrLeu-Asp-Ser-Arg-Arg-Ala-GlnAsp-Phe-Val-Gln-Trp-Leu-MetAsn-Thr-COOH.
The polypeptide has a molecular
weight of 3485 daltons. Glucagon
is
a
peptide
(nonsteroid)
hormone.
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Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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Hormones
Koolman,
Color Atlas
of
Biochemist
ry, 2nd
edition ©
2005
Thieme
24
Calcitriol and parathyroid hormone, on the one hand,
and calcitonin on the other, ensure a more or less constant level
of Ca2+ in theblood plasma and in the extracellular space (80–
110 mg 2.0–2.6 mM).
The peptide parathyroid hormone (PTH; 84 AA) and
the steroid calcitriol promote direct or indirect processes that
raise the Ca2+ level in blood.
Calcitriol increases Ca2+ resorption in the intestines and
kidneys by inducing transporters.
Parathyroid hormone supports these processes by
stimulating calcitriol biosynthesis in the kidneys. In addition, it
directly promotes resorption of Ca2+ in the kidneys and Ca2+
release from bone.
The PTH antagonist calcitonin (32 AA) counteracts
these processes.
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Koolman,
Color Atlas
of
Biochemistr
y, 2nd
edition ©
2005
Thieme
26
Digestive hormones
HCl secretion is stimulated by the peptide hormone gastrin, the mediator
histamine, and - via the neurotransmitter acetylcholine - by the autonomous
nervous system. The peptide somatostatin and certain prostaglandins have
inhibitory effects. Together with cholecystokinin, secretin, and other peptides,
gastrin belongs to the group of gastrointestinal hormones. All of these are
formed in the gastrointestinal tract andmainly act in the vicinity of the site where
they are formed - i.e., they are paracrine hormones. While gastrin primarily
enhances HCl secretion, cholecystokinin and secretin mainly stimulate pancreatic
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secretion and bile release.
Адаптовано за Кольман Я., Рем К.-Г.
Наглядная биохимия, 2009.
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A. Renal hormones
In addition to their involvement in excretion and
metabolism, the kidneys also have endocrine functions.
They produce the hormones erythropoietin and
calcitriol and play a decisive part in producing the
hormone angiotensin II by releasing the enzyme renin.
Renal prostaglandins have a local effect on Na+
resorption.
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Цитовано за Кольман Я., Рем К.-Г.
Наглядная биохимия, 2009.
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B. Renin–angiotensin system [4]
The peptide hormone angiotensin II is not synthesized in a hormonal gland, but
in the blood. The kidneys take part in this process by releasing the enzyme
renin.
Renin is an aspartate proteinase. It is formed by the kidneys as a precursor
(prorenin), which is proteolytically activated into renin and released into the
blood. In the blood plasma, renin acts on angiotensinogen, a plasma
glycoprotein in the α2-globulin group (see p. 276), which like almost all plasma
proteins is synthesized in the liver. The decapeptide cleaved off by
renin is called angiotensin I. Further cleavage by peptidyl dipeptidase A
(angiotensin-converting enzyme, ACE), a membrane enzyme located on the
vascular endothelium in the lungs and other tissues, gives rise to the
octapeptide angiotensin II, which acts as a hormone and neurotransmitter. The
lifespan of angiotensin II in the plasma is only a few minutes, as it is rapidly
broken down by other peptidases (angiotensinases), which occur in many
different tissues.
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Цитовано: Кольман Я., Рем К.-Г.
Наглядная биохимия, 2009.
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