User:Vrwclemson/Endorphins

GOAL: give a more complete picture and reformat to paragraph form.
To add to History:

Opioid peptides in the brain were first discovered in 1974 by two independent groups of investigators: John Hughes and Hans Kosterlitz. They isolated "enkephalins" (from the Greek εγκέφαλος, cerebrum) from pig brain. They identified peptides of two sequences, identified as Met-enkephalin and Leu-enkephalin. Research during this time was focused on the search for analgesic endogenous compounds to treat and study drug addiction.
 * Hughes and Kosterlitz named Met-enkephalin and Leu-enkephalin.
 * In 1976, Choh Hao Li and David Chung discovered the sequences of α-, γ-, and β-endorphins in their study of peptides with opioid activity.

Rabi Simantov and Solomon H. Snyder isolated morphine-like peptides from calf brain. Eric J. Simon, who independently discovered opioid receptors, would later term these peptides as endorphins. In 1976, Choh Hao Li and David Chung recorded the sequences of α-, β-, and γ-endorphin isolated from camel pituitary glands for their opioid activity. They identified that β-endorphin produced strong analgesic effects.

Studies have subsequently distinguished between enkephalins, endorphins, and endogenously-produced morphine,  which is not a peptide. Opioid peptides are classified based on their precursor propeptide: all endorphins are synthesized from the precursor proopiomelanocortin (POMC), enkephalins encoded by proenkephalin A, and dynorphins encoded by pre-dynorphin.

GOAL: Expand on this section.
Add reference for [alpha] and [gamma]-endorphin sequences.

The endorphins are all synthesized from the precursor protein, proopiomelanocortin and all contain the Met-enkephalin motif at their N-terminus: Tyr-Gly-Gly-Phe-Met.

α-endorphin and γ-endorphin result from proteolytic cleavage of β-endorphin between the Thr(16)-Leu(17) residues and Leu(17)-Phe(18) respectively.

GOAL: be more specific with the synthesis of these peptides
Mammalian endorphin precursors are primarily produced in the pituitary gland. All three types of endorphins are fragments of the precursor protein proopiomelanocortin (POMC). POMC is fragmented into many different smaller proteins, including beta-lipotropin (β-LPH). β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides, including α-endorphin, β-endorphin, and γ-endorphin.

To add:

Pre-POMC contains a N-terminus signal sequence that directs the nascent polypeptide to the endoplasmic reticulum. Removal of the signal sequence signals for the delivery of POMC to the Golgi Apparatus.

At the trans-Golgi network, POMC attaches to a membrane-bound protein, carboxypeptsidase E, which tags POMC proteins to be included in granules budding from the trans-Golgi membrane. In mammals, pro-peptide convertase 1 (PC1) cleaves POMC into adrenocorticotropin (ACTH) and β-LPH. Peptide convertase 2 (PC2) cleaves β-LPH into β-endorphin and γ-lipotropin.

GOAL: reorganize
Endorphin precursors are primarily produced in the pituitary gland. All three types of endorphins are fragments of the precursor protein proopiomelanocortin (POMC). Within cells, newly synthesized pre-POMC polypeptide contains a N-terminus signal sequence that directs it to the endoplasmic reticulum and the Golgi Apparatus thereafter. At the trans-Golgi network, POMC binds to a membrane-bound protein, carboxypeptidase E (CPE). CPE facilitates POMC transport into immature budding vesicles. In mammals, pro-peptide convertase 1 (PC1) cleaves POMC into adrenocorticotropin (ACTH) and β-LPH. β-LPH, a pituitary hormone with little opiate activity, is then continually fragmented into different peptides, including α-endorphin, β-endorphin, and γ-endorphin. Peptide convertase 2 (PC2) is responsible for cleaving β-LPH into β-endorphin and γ-lipotropin. Formation of α-endorphin and γ-endorphin results from proteolytic cleavage of β-endorphin.