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BIOCHEMISTRY
Hormones and related
biosignaling compounds
part 1
The major endocrine system and their target tissues
One of the mechanisms of
regulation in stress and disease
Hypothalamus and pituitary gland
(anterior posterior portion)
Sponsored
Medical Lecture Notes – All Subjects
USMLE Exam (America) – Practice
Hypothalamus hormons (releasing factors)
International Union of Pure
and Applied Chemistry –
IUPAC (1974) classification
Corticoliberin
{corticostatin}
Somatoliberin
Somatostatin
Thyroliberin
Gonadoliberin
{prolactoliberin}
Prolactostatin
{melanoliberin}
{melanostatin}
Corticoliberin – corticotropin-releasing hormone
НООС-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-
His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-
Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-
Glu-Ile-Ile-NH2
{corticostatin – not discoverd yet, but some corticostatin-like
funcions are released by glucocorticoids}
Somatoliberin – somatotropin-releasing hormon
НООС-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-
Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-
Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-
Gly-Ala-Arg-Ala-Arg-Leu-NH2
(acromegalia)
dicovered in 1964, final sequence of amino acids dicoversd
in 1981
Somatostatin
Somatostatin -14 (SST-14 – tetradecapetide):
Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys
S-------------------------------------------------------------S
| |
Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys
Somatostatin -28 (SST-28):
Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys-Ala-Gly-Cys-Lys-Asn-
Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys
Thyroliberin – thyrotropin-releasing hormone
(discovered in 1970) consists of 3 amino acids. But its
synthesis started with preprothyroliberin, which consists of
242 amino acid residue (AAR)
Gonadoliberin (luliberin, foliberin)
pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
{prolactoliberin – prolactin-releasing hormon is not
discoverd yet, but it is proved, that prolactin secretion
stimulating function is released by thyroliberin and
vasoactive intestinal peptid [VIP]}
Prolactostatin
consists of 56 AAR –
function: decrease the production of prolactin
{melanoliberin - stimulate release of the
melanocytstimulating hormone in animals – but not
discovered yet in human}
{melanostatin – inhibit stimulate release of the
melanocytstimulating hormone in animals – but not
discovered yet in human}
There are also other active compounds
P substance , gastroliberating peptide, vasoactive peptide,
YY peptide, secretin, histidine-methionin-27 peptide,
Y neuropeptide, neurotesin, motilin, catacalcin, galanin,
calcitonin, angiotensin-І and angiotensin-ІI,
α-atrium natriuretic peptide-32,
brain atrium natriuretic peptide-32,
cholecist octapeptid
and other
possible (for sure) there are other hormones
we do not know yet…
Most of releasing hypophistropic hormones (liberins and
statins) are secreted by neurons of hypothalamus, which are
located in
paraventricular nucleus (thyroliberin, corticoliberin)
nucleus arcuatus (somatoliberin, prolactin, [dofamin])
anterior part of hypothalamus (somatostatin)
anterior-optical part of hypothalamus (gonadoliberin)
HYPOPHYSIS (pituitary body)
Main groups of pituitary (hypophysis) hormones:
proopiomelanocortin group
somatotropin-prolactin-chorionic-somatotropin group
glycoproteinic hormones
posterior pituitary hormones
proopiomelanocortin group:
adrenocorticotropic hormone (ACTH) [NН2–Сер–Тир–Сер–Мет–Глу–Гіс–
Фен–Арг–Три–Глі–Ліз–Про–Вал–Глі–Ліз–Ліз–Арг–
Арг–Про–Вал–Ліз–Вал–Тир–Про–Аса–Глі–Ала–Глу–Асп–Глу–Сер–Ала–Глу–Ала–Фен–
Про–Лей–Глу–Фен–OH]
α-melanicytstimulating hormone
[СН3-СО-NH-Сер–Тир–Сер–Мет–Глу–Гис–Фен–Арг–Трп–Гли–Лиз–Про–Вал-СО-NН2 ]
β-melanicytstimulating hormone
[Н-Ала–Глу–Лиз–Лиз–Асп–Глу–Гли–Про–Тир–Aрг–Мет–Глу–Гис–Фен–Арг–Трп–Гли–
Сер–Про–Про–Лиз–Асп-ОН ]
γ-melanicytstimulating hormone
Corticotropin Like Intermediate Peptide (CLIP)
β-lipotropin (β-lipotropic hormone)
[N-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-
Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu]
γ-lipotropin (γ-lipotropic hormone)
proopiomelanocortin group:
β-endorphin
[N-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-
Ala-Ile-Ile--Asn-Ala-Tyr-Lys-Lys-Gly-Glu ]
met-encephalin
[H3N – TRY – GLY – GLY – PHE – MET – COO– ]
leu-encephalin
[H3N – TRY – GLY – GLY – PHE – LEU – COO– ]
Pro-opiomelanocortin (POMC)
is a precursor polypeptide with 241 amino acid residues (AAR).
POMC is synthesized from the 285-amino-acid-long polypeptide
precursor pre-pro-opiomelanocortin (pre-POMC),
by the removal of a 44-amino-acid-long signal peptide sequence
during translation.
Proopiomelanocortin (POMC) – proteolytic
processing and derivates
Lipotropin. β-Lipotropin (Gamma lipotropin)
is a hormone produced by the cleavage of POMC. The anterior pituitary
gland produces the pro-hormone POMC, which is then cleaved again to
form adrenocorticotropin (ACTH) and β-lipotropin (β-LPH).
β-Lipotropin is a 90-AAR polypeptide that is the carboxy-
termonal fragment of POMC.
It stimulates melnocytes to produce melanin, and can also be cleaved into
smaller peptides. In humans, γ-lipotropin, β-MSH, and β- endorphin, are
all possible fragments of β-lipotropin.[1]
β-Lipotropin also performs lipid-mobilizing functions such
as lipolysis and steroidogenesis. β-Lipotropin is the predominant opioid
of the anterior human and rat pituitary gland. It is found in essentially
equimolar concentrations to that of corticotropin. Evidence shows that β-
Lipotropin is metabolized into endorphins that can greatly affect mood
and behavior and is thus regarded as a prohormone.
γ-Lipotropin (Gamma lipotropin)
γ-lipotropin is the amono-terminal peptide fragment of β-lipotropin. In
humans, it has 56 amino acids. Gamma lipotropin is identical to the first
56 amino acid sequences of β-lipotropin. It can be cleaved to
β-melanocyte stimulating hormone.
Lipotropin has also, under its alternate name AOD-9604 (Anti-Obesity
Drug-9604).
Allegations have arisen around the use of the drug and its administration
to players of sports teams as a supplement, including weekly
administration to players. The matters are currently under investigation
due to the relationship between Lipotropin and growth hormones, as
noted by medical staff.
Melanocyte-Stimulating hormones (MSH)
α-MSH:
Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val
β-MSH (human):
Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-
Pro-Lys-Asp
β-MSH (porcine):
Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
γ-MSH:
Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly
An increase in MSH will cause darker skin in humans. MSH increases in
humans during pregnancy. This, along with increased estrogenes, causes
increased pigmentation in pregnant women. Cushing’s syndrome due to
excess adrenocorticotropic hormone (ACTH) may also result in
hyperpigmentation, such as acanthosis nigricans in the axilla.
somatotropin-prolactin-chorionic-somatotropin group:
somatotropin hormone
prolactin hormone
chorionic-somatotropin hormone
Prolactine
glycoproteinic hormons
thyreotropic hormone
gonadotropic hormone
pholiculostymulating hormone
lutheinic hormone
chorionic-gonadotropic hormone
Gonadotropin
posterior pituitary:
Oxytocin and Vasopressin (untidiuretic hormone)
INSULIN
Frederic Sanger (1955) – 51 amino acid residue
5.7 kdalton A-chain consist of 21 and B-chain of 30AAR
(secreted by β-c elle of Langergance insulas)
Insulin regulate the blood glucose level
Primary structure of insulin in different animal is different
Space forms of insulin
Insulin exist in mono-, bis-, and hexamer forms. Hexameric
form is stabilised by Zn2+ ions through histidin amino acid
(His10) in B-chain in each insulin molecule.
Insulin synthesis in ribosomes
1 signal peptid synthesis
2 preproinsulin synthesis
3 signal peptid cleavege
4 transport to Golgi
apparatus
5 proinsulin transforming into
insulin granulas
6 secretion of insulin
Amino acid sequence of porcine proinsilin
A chain is shown in red, the B chain in blue, the connecting peptide (C-
peptide) in yellow.
Enzymatic conversion of
preproinsulin into proinsulin
and then into insulin
Some mechanisms connected with insulin
GLUCAGONE
like insulin antagonist. Peptide of 29 AARmolecular
weigh 3,5 kD [kilodalton] (3485 D). Глюкагон було
Discovered in 1923. AAR sequence as next:
NH2-His-Ser-Gln-Gly-Thr-Phe- Thr-Ser-Asp-Tyr-
Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-
Phe-Val-Gln-Trp-Leu- Met-Asn-Thr-COOH
Thyroid, parathyroid gland
Thyroid hormone synthesis
Thyroid hormone TRIJODTHYRON
TETRAIODTHYRONIN
THYROXINE (T4)
TRIJODTHYRONIN
(T3)
Parathyroid hormone
Parathyroid hormone(parathormone) – polipeptide of
84AAR
Molecular weigh 9,5 kD
Pro-parathormone >
(protrolitic cleave – 6 AAR in N ending)>
parathormone
GASTROINTESTINAL HORMONES
GASTRIN
Is produced by G-cells of stomach, mainli located in antral part, and by
D-cells of pancreas. Main form of gastin are:
Gastrin-34 or “Big- Gastrin” – polipeptide of 34AAR,
Gastrin-17 або “Little Gastrin”, - 17AAR
(pGlu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-
Asp-Phe-NH2), and Gastrin-14 or “MiniGastrin” – 14AAR.
All gastrins are homological in chemical structure of there active part of
5AAR (which bond with speciphic garstrin-receptors)
...-Gly-Trp-Met-Asp-Phe-NH2.
But rhe gastrin activity show simply fourAAR
…-Trp-Met-Asp-Phe-NH2
This part made the arteficial – pentagastrin –
Gastrin-34 secreted mainly by pancreas,
Gastrin-17 and Gastrin-14 – mainly in spomach.
Forms of Gastrin and artificial - pentagastrin
Big-Gastrin
Little-Gastrin
Mini-Gastrin
Pentagastrin
Gastrin cleave
CHOLECYSTOKININ
.
Cholecystokinin (CCK or CCK-PZ) is similar to gastrin – they have
identical sequenses ofAAR:
...-Gly-Trp-Met-Asp-Phe-...
Cholecystokinin was discovered “twice”. First time in 1928, in mucose
part of stomach as peptide which regulate contraction of gall bladder, and
bile injection into duodenum, and based on this property was named
Cholecystokinin; (chole – bile, kýstis – vesica; kieō – to move).
In 1943, – in mucose of thin intestine was fined peptide, which could
stimulate pancreatic secretion – for this property was named
pancreozymin. In 60-th was determined the absolute similarity of
Cholecystokinin an Pancreozymin.
Cholecystokinin forms
Cholecystokinin [CCK] othe word: pancreosimin, – like gastrin, has some variants:
Cholecystokinin-58 (CCK58),
Cholecystokinin-58-desnonopeptide (means CCK58 whithout nine AAR – (1-49)-CCK58),
Cholecystokinin-39 (CCK39),
Cholecystokinin-33 (CCK33),
Cholecystokinin-25 (CCK25),
Cholecystokinin-18 (CCK18),
Cholecystokinin-8 (CCK8),
Cholecystokinin-7 (CCK7)
Cholecystokinin-5 (CCK5)
Cholecystokinin-4 (CCK4)
Mainly typical Cholecystokinins are
Cholecystokinin-33,
Cholecystokinin-12
Cholecystokinin-8.
Sequence of AAR in Cholecystokinin-33is:
H-Lys-Ala-Pro-Ser-Gly-Arg-Val-Ser-Met-lle-Lys-Asn-Leu-GIn-Ser-Leu-Asp-Pro-Ser-His-Arg-
lle-Ser-Asp-Arg-Asp-Tyr- Met-Gly-Trp-Met-Asp-Phe-OH.
Cholecystokinin-8 makes 60-70% of all compounds o the class
SECRETIN
Molecular weigh – 3,1 kD (3055 D).
Consists of 27 AAR (amidid С ending of valin) :
H2N–His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-
Leu-Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly-
Leu-Val-CONH2.
Molecule of secretin has helix-like formation in region of 5
and 13AAR.
Secretin is similar to:
glucagone (similar sequence of 14 AAR), also it has similar to
gactric inhibitin peptide [GIP] (similar sequence of 10 AAR),
there some similarity with vasoactive intestinal peptide [VIP]
(similar sequence of 7AAR).
Hormon compounds homologic to secretin
Vasoactive intestinal peptide [VIP]
Glucose-dependent insulintropic polipeptide
Glucagons-like peptid-1
Pituitary adenylatecyclase activating polypeptide
RENIN in renin-agiotensine system 1
RENIN in renin-agiotensine system 2
NATRIURETIC PEPTIDES
Atrial natriuretic
peptides [ANP],
brain natriuretic
peptides [BNP]
And
C-type natriuretic
peptides [CNP]
Structure (common sequences
of ANP, BNP, CNP indicated
in green)
Human ENDOTHELIN-1
Generation of
endothelin-1 in
the vascular
endothelium
Norepinephrine
Epinephrine synthesis
Thyramine
Histamine synthesis
GABA (γ-aminobutyrate) synthesis
Serotonine synthesis
Steroid hormone
Steroid
hormon
synthesis
PREDNISOLONUM
Thank YOU for ATTENTION

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Hormones & related bio signaling compounds (Part 1)

  • 2. The major endocrine system and their target tissues
  • 3. One of the mechanisms of regulation in stress and disease
  • 4. Hypothalamus and pituitary gland (anterior posterior portion)
  • 5. Sponsored Medical Lecture Notes – All Subjects USMLE Exam (America) – Practice
  • 6. Hypothalamus hormons (releasing factors) International Union of Pure and Applied Chemistry – IUPAC (1974) classification Corticoliberin {corticostatin} Somatoliberin Somatostatin Thyroliberin Gonadoliberin {prolactoliberin} Prolactostatin {melanoliberin} {melanostatin}
  • 7. Corticoliberin – corticotropin-releasing hormone НООС-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe- His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu- Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met- Glu-Ile-Ile-NH2 {corticostatin – not discoverd yet, but some corticostatin-like funcions are released by glucocorticoids}
  • 8. Somatoliberin – somatotropin-releasing hormon НООС-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys- Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp- Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg- Gly-Ala-Arg-Ala-Arg-Leu-NH2 (acromegalia) dicovered in 1964, final sequence of amino acids dicoversd in 1981
  • 9. Somatostatin Somatostatin -14 (SST-14 – tetradecapetide): Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys S-------------------------------------------------------------S | | Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys Somatostatin -28 (SST-28): Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys-Ala-Gly-Cys-Lys-Asn- Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys
  • 10. Thyroliberin – thyrotropin-releasing hormone (discovered in 1970) consists of 3 amino acids. But its synthesis started with preprothyroliberin, which consists of 242 amino acid residue (AAR)
  • 12. {prolactoliberin – prolactin-releasing hormon is not discoverd yet, but it is proved, that prolactin secretion stimulating function is released by thyroliberin and vasoactive intestinal peptid [VIP]} Prolactostatin consists of 56 AAR – function: decrease the production of prolactin
  • 13. {melanoliberin - stimulate release of the melanocytstimulating hormone in animals – but not discovered yet in human} {melanostatin – inhibit stimulate release of the melanocytstimulating hormone in animals – but not discovered yet in human}
  • 14. There are also other active compounds P substance , gastroliberating peptide, vasoactive peptide, YY peptide, secretin, histidine-methionin-27 peptide, Y neuropeptide, neurotesin, motilin, catacalcin, galanin, calcitonin, angiotensin-І and angiotensin-ІI, α-atrium natriuretic peptide-32, brain atrium natriuretic peptide-32, cholecist octapeptid and other possible (for sure) there are other hormones we do not know yet…
  • 15. Most of releasing hypophistropic hormones (liberins and statins) are secreted by neurons of hypothalamus, which are located in paraventricular nucleus (thyroliberin, corticoliberin) nucleus arcuatus (somatoliberin, prolactin, [dofamin]) anterior part of hypothalamus (somatostatin) anterior-optical part of hypothalamus (gonadoliberin)
  • 17. Main groups of pituitary (hypophysis) hormones: proopiomelanocortin group somatotropin-prolactin-chorionic-somatotropin group glycoproteinic hormones posterior pituitary hormones
  • 18. proopiomelanocortin group: adrenocorticotropic hormone (ACTH) [NН2–Сер–Тир–Сер–Мет–Глу–Гіс– Фен–Арг–Три–Глі–Ліз–Про–Вал–Глі–Ліз–Ліз–Арг– Арг–Про–Вал–Ліз–Вал–Тир–Про–Аса–Глі–Ала–Глу–Асп–Глу–Сер–Ала–Глу–Ала–Фен– Про–Лей–Глу–Фен–OH] α-melanicytstimulating hormone [СН3-СО-NH-Сер–Тир–Сер–Мет–Глу–Гис–Фен–Арг–Трп–Гли–Лиз–Про–Вал-СО-NН2 ] β-melanicytstimulating hormone [Н-Ала–Глу–Лиз–Лиз–Асп–Глу–Гли–Про–Тир–Aрг–Мет–Глу–Гис–Фен–Арг–Трп–Гли– Сер–Про–Про–Лиз–Асп-ОН ] γ-melanicytstimulating hormone Corticotropin Like Intermediate Peptide (CLIP) β-lipotropin (β-lipotropic hormone) [N-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn- Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu] γ-lipotropin (γ-lipotropic hormone)
  • 19. proopiomelanocortin group: β-endorphin [N-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn- Ala-Ile-Ile--Asn-Ala-Tyr-Lys-Lys-Gly-Glu ] met-encephalin [H3N – TRY – GLY – GLY – PHE – MET – COO– ] leu-encephalin [H3N – TRY – GLY – GLY – PHE – LEU – COO– ]
  • 20. Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues (AAR). POMC is synthesized from the 285-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-amino-acid-long signal peptide sequence during translation.
  • 21. Proopiomelanocortin (POMC) – proteolytic processing and derivates
  • 22. Lipotropin. β-Lipotropin (Gamma lipotropin) is a hormone produced by the cleavage of POMC. The anterior pituitary gland produces the pro-hormone POMC, which is then cleaved again to form adrenocorticotropin (ACTH) and β-lipotropin (β-LPH). β-Lipotropin is a 90-AAR polypeptide that is the carboxy- termonal fragment of POMC. It stimulates melnocytes to produce melanin, and can also be cleaved into smaller peptides. In humans, γ-lipotropin, β-MSH, and β- endorphin, are all possible fragments of β-lipotropin.[1] β-Lipotropin also performs lipid-mobilizing functions such as lipolysis and steroidogenesis. β-Lipotropin is the predominant opioid of the anterior human and rat pituitary gland. It is found in essentially equimolar concentrations to that of corticotropin. Evidence shows that β- Lipotropin is metabolized into endorphins that can greatly affect mood and behavior and is thus regarded as a prohormone.
  • 23. γ-Lipotropin (Gamma lipotropin) γ-lipotropin is the amono-terminal peptide fragment of β-lipotropin. In humans, it has 56 amino acids. Gamma lipotropin is identical to the first 56 amino acid sequences of β-lipotropin. It can be cleaved to β-melanocyte stimulating hormone. Lipotropin has also, under its alternate name AOD-9604 (Anti-Obesity Drug-9604). Allegations have arisen around the use of the drug and its administration to players of sports teams as a supplement, including weekly administration to players. The matters are currently under investigation due to the relationship between Lipotropin and growth hormones, as noted by medical staff.
  • 24. Melanocyte-Stimulating hormones (MSH) α-MSH: Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val β-MSH (human): Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro- Pro-Lys-Asp β-MSH (porcine): Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp γ-MSH: Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly An increase in MSH will cause darker skin in humans. MSH increases in humans during pregnancy. This, along with increased estrogenes, causes increased pigmentation in pregnant women. Cushing’s syndrome due to excess adrenocorticotropic hormone (ACTH) may also result in hyperpigmentation, such as acanthosis nigricans in the axilla.
  • 27. glycoproteinic hormons thyreotropic hormone gonadotropic hormone pholiculostymulating hormone lutheinic hormone chorionic-gonadotropic hormone
  • 29. posterior pituitary: Oxytocin and Vasopressin (untidiuretic hormone)
  • 30. INSULIN Frederic Sanger (1955) – 51 amino acid residue 5.7 kdalton A-chain consist of 21 and B-chain of 30AAR (secreted by β-c elle of Langergance insulas) Insulin regulate the blood glucose level Primary structure of insulin in different animal is different
  • 31. Space forms of insulin Insulin exist in mono-, bis-, and hexamer forms. Hexameric form is stabilised by Zn2+ ions through histidin amino acid (His10) in B-chain in each insulin molecule.
  • 32. Insulin synthesis in ribosomes 1 signal peptid synthesis 2 preproinsulin synthesis 3 signal peptid cleavege 4 transport to Golgi apparatus 5 proinsulin transforming into insulin granulas 6 secretion of insulin
  • 33. Amino acid sequence of porcine proinsilin A chain is shown in red, the B chain in blue, the connecting peptide (C- peptide) in yellow.
  • 34. Enzymatic conversion of preproinsulin into proinsulin and then into insulin
  • 36. GLUCAGONE like insulin antagonist. Peptide of 29 AARmolecular weigh 3,5 kD [kilodalton] (3485 D). Глюкагон було Discovered in 1923. AAR sequence as next: NH2-His-Ser-Gln-Gly-Thr-Phe- Thr-Ser-Asp-Tyr- Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp- Phe-Val-Gln-Trp-Leu- Met-Asn-Thr-COOH
  • 40. Parathyroid hormone Parathyroid hormone(parathormone) – polipeptide of 84AAR Molecular weigh 9,5 kD Pro-parathormone > (protrolitic cleave – 6 AAR in N ending)> parathormone
  • 41. GASTROINTESTINAL HORMONES GASTRIN Is produced by G-cells of stomach, mainli located in antral part, and by D-cells of pancreas. Main form of gastin are: Gastrin-34 or “Big- Gastrin” – polipeptide of 34AAR, Gastrin-17 або “Little Gastrin”, - 17AAR (pGlu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met- Asp-Phe-NH2), and Gastrin-14 or “MiniGastrin” – 14AAR. All gastrins are homological in chemical structure of there active part of 5AAR (which bond with speciphic garstrin-receptors) ...-Gly-Trp-Met-Asp-Phe-NH2. But rhe gastrin activity show simply fourAAR …-Trp-Met-Asp-Phe-NH2 This part made the arteficial – pentagastrin – Gastrin-34 secreted mainly by pancreas, Gastrin-17 and Gastrin-14 – mainly in spomach.
  • 42. Forms of Gastrin and artificial - pentagastrin Big-Gastrin Little-Gastrin Mini-Gastrin Pentagastrin
  • 44. CHOLECYSTOKININ . Cholecystokinin (CCK or CCK-PZ) is similar to gastrin – they have identical sequenses ofAAR: ...-Gly-Trp-Met-Asp-Phe-... Cholecystokinin was discovered “twice”. First time in 1928, in mucose part of stomach as peptide which regulate contraction of gall bladder, and bile injection into duodenum, and based on this property was named Cholecystokinin; (chole – bile, kýstis – vesica; kieō – to move). In 1943, – in mucose of thin intestine was fined peptide, which could stimulate pancreatic secretion – for this property was named pancreozymin. In 60-th was determined the absolute similarity of Cholecystokinin an Pancreozymin.
  • 45. Cholecystokinin forms Cholecystokinin [CCK] othe word: pancreosimin, – like gastrin, has some variants: Cholecystokinin-58 (CCK58), Cholecystokinin-58-desnonopeptide (means CCK58 whithout nine AAR – (1-49)-CCK58), Cholecystokinin-39 (CCK39), Cholecystokinin-33 (CCK33), Cholecystokinin-25 (CCK25), Cholecystokinin-18 (CCK18), Cholecystokinin-8 (CCK8), Cholecystokinin-7 (CCK7) Cholecystokinin-5 (CCK5) Cholecystokinin-4 (CCK4) Mainly typical Cholecystokinins are Cholecystokinin-33, Cholecystokinin-12 Cholecystokinin-8. Sequence of AAR in Cholecystokinin-33is: H-Lys-Ala-Pro-Ser-Gly-Arg-Val-Ser-Met-lle-Lys-Asn-Leu-GIn-Ser-Leu-Asp-Pro-Ser-His-Arg- lle-Ser-Asp-Arg-Asp-Tyr- Met-Gly-Trp-Met-Asp-Phe-OH. Cholecystokinin-8 makes 60-70% of all compounds o the class
  • 46. SECRETIN Molecular weigh – 3,1 kD (3055 D). Consists of 27 AAR (amidid С ending of valin) : H2N–His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg- Leu-Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly- Leu-Val-CONH2. Molecule of secretin has helix-like formation in region of 5 and 13AAR. Secretin is similar to: glucagone (similar sequence of 14 AAR), also it has similar to gactric inhibitin peptide [GIP] (similar sequence of 10 AAR), there some similarity with vasoactive intestinal peptide [VIP] (similar sequence of 7AAR).
  • 47. Hormon compounds homologic to secretin Vasoactive intestinal peptide [VIP] Glucose-dependent insulintropic polipeptide Glucagons-like peptid-1 Pituitary adenylatecyclase activating polypeptide
  • 50. NATRIURETIC PEPTIDES Atrial natriuretic peptides [ANP], brain natriuretic peptides [BNP] And C-type natriuretic peptides [CNP] Structure (common sequences of ANP, BNP, CNP indicated in green)
  • 51. Human ENDOTHELIN-1 Generation of endothelin-1 in the vascular endothelium
  • 60. Thank YOU for ATTENTION