Pyridoxal phosphate-dependent reaction

Write a reasonable mechanism for the 3-ketosphinganine synthase reaction, remembering that it is a pyridoxal phosphate-dependent reaction. 

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

Most people have heard of antihistamines, even if they have little concept of the nature of histamine. Histamine is the decarboxylation product from histidine, and is formed from the amino acid by the action of the enzyme histidine decarboxylase. The mechanism of this pyridoxal phosphate-dependent reaction will be studied in more detail later (see Section 15.7). 

This enzyme [EC 2.6.1.2], also known as glutamic-pyruvic transaminase and glutamic-alanine transaminase, catalyzes the pyridoxal-phosphate-dependent reaction of alanine with 2-ketoglutarate, resulting on the production of pyruvate and glutamate. 2-Aminobutanoate will also react, albeit slowly. There is another alanine aminotransferase [EC 2.6.1.12], better known as alanine-oxo-acid aminotransferase, which catalyzes the pyridoxal-phosphate-dependent reaction of alanine and a 2-keto acid to generate pyruvate and an amino acid. See also Alanine Glyoxylate Aminotransferase... 

This enzyme [EC 2.6.1.21], also known as D-aspartate aminotransferase, D-amino acid aminotransferase, and D-amino acid transaminase, catalyzes the reversible pyridoxal-phosphate-dependent reaction of D-alanine with a-ketoglutarate to yield pyruvate and D-glutamate. The enzyme will also utilize as substrates the D-stereoisomers of leucine, aspartate, glutamate, aminobutyrate, norva-hne, and asparagine. See o-Amino Acid Aminotransferase... 

This enzyme [EC 2.6.1.18], also known as j8-alanine-pyruvate aminotransferase, catalyzes the reversible pyridoxal-phosphate-dependent reaction of /3-alanine with pyruvate to generate 3-oxopropanoate and alanine. 

Amino acid decarboxylation takes place by the removal of the a-carboxyl group to give the corresponding amine. Two mechanisms of action have been identified which include a pyridoxal phosphate dependent reaction and a non-pyridoxal phosphate dependent reaction. 

PLP. See Pyridoxal phosphate (PLP) PLP-dependent reactions. See Pyridoxal phosphate-dependent reactions PNA, 227s... 

Structures of catalytic intermediates in pyridoxal-phosphate-dependent reactions. The initial aldimine intermediate resulting from Schiff s base formation between the coenzyme and the a-amino group of an amino acid (a). This aldimine is converted to the resonance-stabilized... 

Pyridoxal phosphate-dependent reactions involving C -C02H bond cleavage... 

In vitamin Bg-deficient experimental animals there are more or less specific skin lesions (e.g., acrodynia in the rat) and fissures or ulceration at the corners of the mouth and over the tongue, as well as a number of endocrine abnormalities, defects in the metabolism of tryptophan, methionine, and other amino acids, hypochromic microcytic anemia (the first step of heme biosynthesis is a pyridoxal phosphate-dependent reaction), changes in leucocyte count and activity, a tendency to epileptiform convulsions, and peripheral nervous system damage resulting in ataxia and sensory neuropathy. 

---