Is there an enzyme supplement for Prohormone Convertase 1 (PC1)?

No Enzyme Supplement for Prohormone Convertase 1 (PC1) Currently Available

There is currently no commercially available enzyme supplement for Prohormone Convertase 1 (PC1) deficiency. Based on the available medical literature, no specific enzyme replacement therapy exists for this condition.

Understanding Prohormone Convertase 1 (PC1)

• PC1 (also known as PC3) is a serine proteinase responsible for the proteolytic processing of many precursor proteins within the regulated secretory pathway 1
• It functions as an endopeptidase that is structurally related to the yeast subtilisin-like Kex2 gene product and is involved in mammalian tissue-specific prohormone processing at pairs of basic residues 2
• PC1 is a calcium-dependent proteinase with optimal activity at pH 5.5-6.5, distinguishing it from related enzymes 3

Current Understanding of PC1 Regulation

• PC1 activity is potentially regulated by two endogenous inhibitors: the PC1 propeptide and proSAAS 1
• The most potent natural inhibitor of PC1 is a decapeptide from proSAAS (proSAAS-235-244: VLGALLRVKR) with a Ki of approximately 9 nM 4
• PC1 exists in both soluble and membrane-tethered forms, with the membrane-tethered version showing greater stability and activity 5

Management Approaches in the Absence of Enzyme Supplements

• For metabolic disorders requiring enzyme supplementation, management typically focuses on preventing metabolic decompensation through emergency protocols during illness or fasting periods 6
• Similar to other enzyme deficiencies, management would likely involve:
  • Developing individualized emergency protocols 6
  • Ensuring adequate caloric intake during illness to prevent catabolism 6
  • Providing aggressive intravenous hydration during metabolic crises 6

Research Limitations and Challenges

• Unlike some other enzyme deficiencies (such as C1 inhibitor deficiency in hereditary angioedema), PC1 does not currently have a plasma-derived or recombinant replacement therapy 7
• The complex nature of PC1's role in the regulated secretory pathway makes development of an effective enzyme supplement challenging 1, 3
• PC1's specific pH requirements (5.5-6.5) and calcium dependency would present challenges for oral enzyme replacement 3

Future Directions

• Research into PC1 inhibitors like proSAAS-derived peptides may provide insights into potential therapeutic approaches 4
• Understanding the structural requirements for PC1 activity could guide development of recombinant versions with improved stability 5
• Management strategies used for other enzyme deficiencies might inform approaches to PC1 deficiency until specific treatments become available 6