Zinc homeostasis also plays a critical role in the functional regulation of the central nervous system. Dysregulation of zinc homeostasis in the central nervous system that results in excessive synaptic zinc concentrations is believed to induce neurotoxicity through mitochondrial oxidative stress (e.g., by disrupting certain enzymes involved in the electron transport chain, including complex I, complex III, and α-ketoglutarate dehydrogenase), the dysregulation of calcium homeostasis, glutamatergic neuronal excitotoxicity, and interference with intraneuronal signal transduction. L- and D-histidine facilitate brain zinc uptake. SLC30A3 is the primary zinc transporter involved in cerebral zinc homeostasis. Enzymes
Zinc is an efficient Lewis acid, making it a useful catalytic agent in hydroxylation and other enzymatic reactions. The metal also has a flexible coordination geometry, which allows proteins using it to rapidly shift conformations to perform biological reactions. Two examples of zinc-containing enzymes are carbonic anhydrase and carboxypeptidase, which are vital to the processes of carbon dioxide (CO2) regulation and digestion of proteins, respectively.In vertebrate blood, carbonic anhydrase converts CO2 into bicarbonate and the same enzyme transforms the bicarbonate back into CO2 for exhalation through the lungs. Without this enzyme, this conversion would occur about one million times slower at the normal blood pH of 7 or would require a pH of 10 or more. The non-related β-carbonic anhydrase is required in plants for leaf formation, the synthesis of indole acetic acid (auxin) and alcoholic fermentation.Carboxypeptidase cleaves peptide linkages during digestion of proteins.
Roflumilast, sold under the trade name Daxas among others, is a drug that acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects and is used as an orally administered drug for the treatment of inflammatory conditions of the lungs such as chronic obstructive pulmonary disease (COPD).In June 2010, it was approved in the European Union for severe COPD associated with chronic bronchitis. In February 2011, it gained FDA approval in the United States for reducing COPD exacerbations. Medical uses
Roflumilast is indicated for the treatment of severe chronic obstructive pulmonary disease (COPD) and for the treatment of plaque psoriasis.It is used in the prevention of exacerbations (lung attacks) in severe chronic obstructive pulmonary disease (COPD).A topical formulation of Rolflumilast was recently approved by the U.S. Food and Drug Administration for plaque psoriasis. Adverse effects
Common (1–10% incidence) adverse effects include:
Diarrhea
Weight loss
Nausea
Headache
Insomnia
Decreased appetite
Abdominal pain
Rhinitis
Sinusitis
Urinary tract infection
Depression

References
External links
"Roflumilast". Drug Information Portal. U.S. National Library of Medicine.