Pyridoxamine-5 -phosphate coenzyme function

FIGURE 18-5 Pyridoxal phosphate, the prosthetic group of aminotransferases. (a) Pyridoxal phosphate (PLP) and its aminated form, pyridoxamine phosphate, are the tightly bound coenzymes of aminotransferases. The functional groups are shaded, (b) Pyridoxal phosphate is bound to the enzyme through noncovalent interactions and a Schiff-base linkage to a Lys residue at the active site. The steps in the formation of a Schiff base from a primary amine and a carbonyl group... 

Peptides, coenzymes, amino acids are special functional biological molecules. They became a hot topic while studying the analogue enzymes. For example, the ALT model was formed by connecting the cofactor pyridoxamine phosphate (pyridoxamine, vitamin Be amine) and ethylenediamine to y3-CD. The two functional groups were located through the intermediate positioning process. 

By transamination, a whole series of other amino adds becomes accessible. Pyridoxal phosphate functions as a coenzyme, which is primarily bonded to a lysine residue of the enzyme. The attack of glutamic acid leads to the corresponding imine. Tautomerisation (proton transfer) and hydrolysis give pyridox-amine phosphate and a-ketoglutaric acid. Pyridoxamine phosphate then reacts with other a-ketoacids, foUowmg the corresponding mechanism. 

The phosphorylated and non-phosphorylated forms of vitamin Bg have various physical and chemical properties. Vitamin Bs in the form of pyridoxal-5 -phosphate (PLP) and to a lesser extent, pyridoxamine-5 -phosphate (PMP), functions as a coenzyme in over 100 enzymatic reactions. All the forms of vitamin Be possess vitamin activity because they can be converted in vivo to pyridoxal. PN, PM and PL are converted to 5 -phosphate by a single kinase enzyme which in the brain and liver is most active with zinc. PNP and PMP are then converted to PLP by flavin dependent oxidase this is the reason why vitamin B2 deficiency causes a fall in available PLP (Holman 1995). Human cells can synthesize PLP from three vitamers via the Bg salvage pathway but cannot synthesize PLP de novo and must obtain it from dietary sources. 

In 1942, Snell discovered the vitamin B-5 activity of two closely related substances in natural products, which he named pyridoxal and pyridoxamine. IJmbreit followed in 1945 with a report of the coenzyme functions of the vitamin in phosphate forms. 

FUNCTIONS. Vitamin B-6, in its coenzyme forms, usually as pyridoxal phosphate but sometimes as pyridoxamine phosphate, is involved in a large number of physiologic functions, particularly in protein (nitrogen) metabolism, and to a lesser extent in carbohydrate and fat metabolism. Also, it appears to hold a key role in a number of chemical problems. Discussion follows ... 

Vitamin Be is again a small family of related compounds having the same biological activity. These include pyridoxine, pyridoxai, and pyridoxamine. In humans, these molecules are readily interconverted, accounting for their equivalence as vitamins. The stuff in your vitamin pill is likely to be pyridoxine. The actual molecule that functions as a coenzyme in metabolism is pyridoxai phosphate, in which a phosphate group has been added to pyridoxai in an ATP-dependent reaction. 

Vitamin Bg is a mixture of six interrelated forms pyridoxine (or pyridoxol) (Figure 19.23), pyri-doxal, pyridoxamine, and their 5 -phosphates derivatives. Interconversion is possible between all forms. The active form of the vitamin is pyridoxal phosphate, which is a coenzyme correlated with the function of more than 60 enzymes involved in transamination, deamination, decarboxylation, or desulfuration reactions. 

Vitamin B6 is a collective term for pyridoxine, pyridoxal, and pyridox amine, all derivatives of pyridine. They differ only in the nature of the functional group attached to the ring (Figure 28.10). Pyridoxine occurs primarily in plants, whereas pyridoxal and pyridoxamine are found in foods obtained from animals. All three compounds can serve as precur sors of the biologically active coenzyme, pyridoxal phosphate. Pyridoxal phosphate functions as a coenzyme for a large number of enzymes, par ticularly those that catalyze reactions involving amino acids. 

Pyridoxal-5 phosphate (P-5 -P) and its amino analogue, pyridoxamine-5 -phosphate, function as coenzymes in the amino-transfer reactions. The P-5 -P is bound to the apoen-zyme and serves as a true prosthetic group. The P-5 -P bound to the apoenzyme accepts the amino group from the first substrate, aspartate or alanine, to form enzyme-bound pyridoxamine-5 -phosphate and the first reaction product, oxaloacetate or pyruvate, respectively. The coenzyme in amino form then transfers its amino group to the second substrate, 2-oxoglutarate, to form the second product, glutamate. P-5 -P is thus regenerated. 

Transaminases also belong to the group of transferases and catalyze desamination and amination reactions. Most amino acids are in equilibrium with the corresponding 0x0-carboxylic acid like alanine and pyruvate. The coenzyme of enzymatic transamination is pyridoxal-5 -phosphate 93, it is one of the most important coenzymes and is in effect the biologically active form of vitamin B6, which is converted to pyridoxamine 94 in this reaction. Besides transamination, pyridoxal-5 -phosphate 93 is also involved in decarboxylation and racemization processes. The aldehyde function of pyridoxal is reacting with the amine of an amino acid to form a Schiff base and thus invers-ing the acidity of the a-CH. The reversible transfer of an... 

Vitamin Bs consists of six forms in nature, i.e. pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), pyridoxine 5 -phosphate (PNP), pyridoxal 5 -phosphate (PLP), and pyridoxamine 5 -phosphate (PMP) (Figure 22.1). PLP is a coenzyme for many enzymes involved in amino acid and carbohydrate metabolism, and plays a key role in the nutritional function of vitamin Bg. The other forms show the same nutritional efficiency because they are converted into PLP in cells. The free forms of vitamin Bg are adsorbed through the intestinal mucosa, and then are phosphorylated and converted into PLP in the liver. Some PLP exits the liver and travels in the blood on albumin, being turned over slowly. PL is the form most actively transported to other cells from the liver. The cells adsorb PL and then phosphorylate it to yield PLP. The final metabolite derived from vitamin Bg is 4-pyridoxic acid (4-PA, Figure 22.1), which is excreted into the urine. Plants contain a storage form of vitamin Bg, pyridoxine-p-glucoside... 

Vitamin Bg consists of pyridoxine (PN) and five related compounds, namely pyridoxal (PL), pyridoxamine (PM) and their respective 5 -phosphates (PEP, PNP and PMP). PLP is the major form in the human body (Figure 42.1). Vitamin Bg functions as a coenzyme in more than 100 enzymatic reactions involved in the metabolism of amino acids, glycogen and sphingoid bases. 

In the tissues, vitamin Be occurs predominantly as the phosphate of pyridoxal or pyridoxamine, especially the former, except in the liver. Pyri-doxal phosphate functions as a coenzyme in four types of reactions decarboxylation of amino acids, transamination, and the synthesis and cleavage of tryptophan (Chapter 19). This coenzyme is necessary for the deamination of amino acids and for the formation of urea nitrogen. It appears to be essential for the conversion of tryptophan to the pyridine coenzymes. Pyridoxine may be related to fatty acid metabolism and seems to be necessary for normal adrenal cortical function. ... 

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