MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY

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MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY ACTH,
MSHs etc
1. ACTH, MSH etc. 2. Structural relationships
between ACTH, MSH etc. Biosynthesis 3. Opioid
peptides 4. Biochemical mode of action of ACTH
and MSH role of MSHs in man (appetite
control) 5. Structure-function relationships
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Sequence alignment of ACTH-related peptides
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Preproopiocortin (Prepro-opiomelanocortin POMC)
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Prohormone converting enzymes
Subtilisin-like serine proteases Cleave after
sequence containing two basic amino acids
(Lys-Lys, Lys-Arg, Arg-Lys, Arg-Arg) Mutation of
PC1 gene gives defects in proinsulin, POMC and
LHRH precursor processing Mutation of PC2 gene
gives defects in proinsulin, proglucagon and
prosomatostatin processing Carboxypeptidases
(CPD, CPE and ?CPM) are needed to complete
processing. Missense mutation of CPE gives
fat/fat mouse - due to incomplete proinsulin
conversion
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ENKEPHALINS
Met-enkephalin Tyr-Gly-Gly-Phe-Met Leu-enkepha
lin Tyr-Gly-Gly-Phe-Leu
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Preproenkephalins
Preproenkephalin A
Preproenkephalin B
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Actions of MSH in humans
1. Skin darkening and antiinflammatory effects
in response to UV light (MC1R) 2. Regulates
feeding/appetite. Interacts with leptin and
other factors. MC4R in hypothalamus. MC4R
mutations can lead to obesity in mice and man 3.
Antiinflammatory effects on various cells of
immune system. Decreases cytokine production by
various immune system cells (esp in brain).
Inhibits NF-kB activation (MC1R, MC3R, MC5R) 4.
Possible actions on exocrine glands (MC5R) 5.
Regulates penile erection and sexual behaviour
(MC4R)
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MELANIN CONCENTRATING HORMONE (MCH)
(From Pissios Maratos-Flier)
Mammalian
Salmon
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Melanotropic activities of some analogues of a-MSH
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Corticotropic activities of some analogues of ACTH