Glutamic acid carboxylase

Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz, SC, Realmuto, GR (2002) Glutamic acid Carboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psych 52 805-810. 

Vitamins K are coenzymes of glutamic acid carboxylase (D 17). In mammals and man naphthoquinones of the vitamin Kg group are formed by the bacteria of the intestine. Phylloquinone is taken up with the diet (vitamin K, E 2.1). 

K, O2, and C02 (Figure 6.6)., The carboxylation of glutamic acid residues of these proteins appears to be directed by a specific recognition sequence, which is often found in the propeptide to insure binding to the vitamin K-dependent carboxylase. Furie et al., (1999) identified five requirements for gamma carboxylation ... 

Gamma carboxylation of glutamic acid residue in a protein. This is an enzymic reaction catalyzed by a carboxylase to modify a glutamic acid residue of a protein to form qamma-carboxyqlutamic acid. The carboxylase reaction requires vitamin K, 02, and C02. 

This. system requires reduced vitamin K (a hydroquinone. KH2). carbon dioxide, and molecular oxygen. Although the reaction docs not require ATP. it u.ses the energy from the oxidation of KH to execute the carboxylation of glutamic acid. " The carboxylase must create a carbanion by extracting a proton from the glutamate y carbon. This requires a base with a pK , of 26 to 28. The anion of the hydroquinone. however, has a pK, of only about 9. 

FIGURE 4.2 The vitamin K cycle as it functions in protein glutamyl carboxylation reaction. The conversion of protein-bound glutamic acid into Y-carboxyglutamic acid is catalysed by a carboxylase. During the carboxylation reaction vitamin K hydroquinone (KH2) is converted to vitamin K epoxide (KO). X—(SH)2 and X—S2 represent, respectively, the reduced and oxidised forms of thioredoxin. The NADH-dependent and dithiol-dependent vitamin K reductases are different enzymes. Both the dithiol-dependent K- and KO-reductases are inhibited by dicoumarol (1) and warfarin (11). 

A gla protein is secreted into the endoplasmic reticulum (ER) of the liver where its N-terminal domain binds to and activates an enzyme that converts glutamic acid residues in the gla domain to y-carboxyglutamic acid. The activated carboxylase enzyme then binds to a reduced form of vitamin K, a diphenol (KH2) to which it adds molecular oxygen. The... 

Figure 11.5 Metabolic pathways related to glutamic acid production in C glutamicum. ICDH, isocitrate dehydrogenase, ODHC, 2-oxoglutarate dehydrogenase complex GDH, glutamate dehydrogenase PPC, phosphoenolpyruvate carboxylase and PC, pyruvate carboxylase.

For the production of glutamic acid, anaplerotic reactions are important to supply oxaloacetate to the TC A cycle for the latter to proceed. C. glutamicum possesses the following two anaplerotic reactions, catalyzed by phosphoenolpyruvate carboxylase (PPC) and pyruvate carboxylase (PC) [63,64] ... 

Vitamine-K-dependent carboxylases first 10 glutamic acid residues in the N-terminal region of the precursor of prothrombin Mn" y-carbo -glutamic acid ... 

Vitamin K is a component of the carboxylase enzyme that carboxylates the amino acid glutamate in proteins to form y-carboxyglutamate, which binds calcium ions i.e. it catalyses a post-transcriptional modification. Proteins so carboxylated include clotting factors (Factors 11, Vll, IX, and X) and two proteins in bone oesteocalcin (known as matrix-gln-protein) and bone gin protein (BGP). The... 

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