Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks: Biomedical implications

Pharmacol Res. 2016 Dec:114:90-102. doi: 10.1016/j.phrs.2016.08.032. Epub 2016 Oct 18.

Abstract

Human histidine decarboxylase (HDC) and dopa decarboxilase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively. The enzymes share many structural and functional analogies, while their product metabolisms also follow similar patterns that are confluent in some metabolic steps. They are involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. As a consequence, metabolic elements of both BA subfamilies are also co-participants in a long list of human diseases. This review summarizes the analogies and differences in their origin (HDC and DDC) as well as their common pathophysiological scenarios. The major gaps of information are also underlined, as they delay the possibility of holistic approaches that would help personalized medicine and pharmacological initiatives for prevalent and rare diseases.

Keywords: Dopamine; Histamine; Molecular interactions; Orphan diseases; Serotonin; Systems pharmacology.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / chemistry
  • Aromatic-L-Amino-Acid Decarboxylases / genetics
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism*
  • Dopamine / metabolism
  • Histamine / metabolism
  • Histidine Decarboxylase / chemistry
  • Histidine Decarboxylase / genetics
  • Histidine Decarboxylase / metabolism*
  • Humans
  • Models, Molecular
  • Rare Diseases / genetics
  • Rare Diseases / metabolism
  • Serotonin / metabolism

Substances

  • Serotonin
  • Histamine
  • Histidine Decarboxylase
  • Aromatic-L-Amino-Acid Decarboxylases
  • Dopamine