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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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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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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) areneeded 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-enkephalin 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