A question about cleavage

Patrick F.H. Lai pfhlai at LOOKSMART.COM
Wed Jul 29 02:18:43 EST 1998

---- Begin Original Message ----
I've read that most hormones are synthesized as prohormones, or 
sometimes as preprohormones. Let's take insulin as an example.

It is synthesized as a preprohormone by polirribosomes attached 
to the RER and then incorporated to the RER because a an ~24-
aminoacid sequence is recognized on it's N-terminal. In the RER, it 
loses this signal and then is sent to the Golgi complex. There it's 
packed for exportation along with some enzymes. During its stay 
in the exportation vesicle, the enzymes cleave the polypeptide 
chain into insulin and peptide C.

My question is how is this cleavage done? I mean, are there 
specific enzymes for each prehormone, or are there signals in the 
aminoacid sequence that indicate where the splitting should occur?

I'm thinking now of POMC. This protein is cleft in different ways 
depending on the cell where the cleavage is performed. I presume 
this must be done by different specific enzymes, because the 
polypeptide is the same in all the cells. Is my assumption correct? 
Does it apply to the other cases?

Thanks in advance,

Jeremias Galletti
Calle 13 Nro. 1442
(6360) General Pico, La Pampa
Tel: 54-302-35583
E-mail: jeremias at teletel.com.ar
---- End Original Message ----

Dear Jeremias,

Just off my head without checking, yes, there are specific enzymes 
that cleave specific prohormones.
Try ACEs (Angiotensin Converting Enzymes) and ECEs (Endothelin 
Converting Enzymes).
(maybe renin is processed similarly, but I forgot.)
For ACEs and ECEs, the regulation of the enzyme activity provides 
another level of complexity to the regulation of hormone level.
Cool, eh !  :-)

And besides POMC, I think the glucagon gene can be similarly expressed
and processed into several hormones / autocoids.

IMHO, protein-cleaving enzymes don't really care what they digest.
If the substrate sequence is present, they cut, cut, cut......
That's how we can release useful peptides from engineered fusion 
proteins using various commercially available kits, right ?

So, I suppose, substrate amino acid sequences may conceivably be 
present in peptides other than the hormone we now know as THE substrate=

And, there may be some common paradigms in peptide hormone synthesis, 
but I don't think the various systems have been fully studied for us 
to appreciate them fully.... at least not yet.

Hope this is useful info.   :-)

Patrick F.H. Lai  < PFHLai at looksmart.com >
Graduate Student
University of Toronto
Toronto, Ontario, Canada

LookSmart =85 or keep looking.

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