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
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
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.
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.
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.
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).