The Role of Histidine in the Anemia of Folate Deficiency

Abstract

The amino acid histidine is metabolized to glutamic acid in mammalian tissue. Formiminoglutamic acid (FIGLU) is an intermediary in this reaction, and tetrahydrofolic acid is the coenzyme that converts it to glutamic acid. A test for folate deficiency concerns the measurement of urinary FIGLU excretion after a histidine load. It was observed that folate-deficient individuals receiving the histidine for the FIGLU test made hematological response that alleviated the anemia associated with this deficiency. This was unusual in that a biochemical test to determine the deficiency results in a beneficial effect for one aspect of the deficiency. The studies reported in this paper give a metabolic explanation for this phenomenon. Urine was collected for 24 hr from 25 folate-deficient subjects, 10 vitamin B12-deficient subjects, and 15 normal controls. Urinary excretion of histidine was a mean of 203 mg with a range of 130–360 mg for the folate-deficient subjects; 51.5 mg with a range of 30–76.6 mg for normal subjects; and 60.0 mg with a range of 32.3–93.0 mg for the vitamin B12-deficient subjects. All the folate-deficient subjects subsequently made a hematological response to the histidine administered for the FIGLU test. No hematological response was observed in the vitamin B12-deficient individuals. When folic acid was given to folate-deficient subjects who received no histidine, urinary histidine levels returned to normal levels rapidly and this was followed by a hematological response. Others have shown that volunteers fed a histidine-free diet developed anemia. In normal subjects, histidine is excreted much more in the urine than other essential amino acids are. Hemoglobin protein contains 10% histidine. Under normal conditions, dietary histidine can supply sufficient histidine to prevent anemia. When the dietary intake is diminished or the urinary excretion is greatly increased, anemia results. It is concluded that folate deficiency causes histidine depletion through increased urinary excretion of this amino acid. Feeding histidine replenishes tissue levels of histidine, resulting in hemoglobin regeneration. Folic acid administration results in return of histidine to normal urinary levels. Thus, a combination of folic acid histidine would be beneficial for folate deficient individuals.

Ribosomal crystallography: Peptide bond formation and its inhibition

“…This simple mechanism is consistent with earlier proposals that the main enzymatic contribution of the ribosome in protein biosynthesis is the provision of a frame for accurate positioning of the tRNA molecules, consistent with results of previous biochemical experiments. 81,83,87,98 In the absence of precise positioning, the inherent flexibility of the peptidyl transferase center allows various binding modes, all requiring conformational rearrangements for participating in peptide-bond formation.…”

“…This mechanism is consistent with the suggestions that the main contribution of the ribosome in catalyzing peptidyl-transferase activity is the provision of a frame for precise positioning of the tRNA molecules. 2,15,16,40,[81][82][83][84][85][86][87] The counter proposal, deduced from the crystal structure of H50S in complex with a partially disordered tRNA-mimic and a material presumed to be a reaction intermediate, claimed that the ribosome participates actively in the enzymatic catalysis of the formation of the peptide bond. 88 Doubt concerning this proposal was raised based on biochemical and mutation data 45,86,89 -91 and recent analysis of structures of additional complexes of the same particle, H50S, further substantiated these uncertainties.…”

“…If not, a spontaneous formation of the peptide bond is implied, as proposed over two decades ago. 81,83 Apart from the GTPase hydrolysis, in comparison to the other steps of protein biosynthesis, the peptidebond formation is considered to be a fast reaction. 101 This irreversible step appears to carry forward the entire protein biosynthesis process, including codonanticodon recognition in the small subunit, the GTPase activation, and the A-site tRNA accommodation in the large subunit.…”

Folat Eksikliği ve Probiyotikler

“…Yetişkinlerde plazma 5-metil-THF değerinin 3-30 ng/mL gibi oldukça geniş bir yelpazede olduğu bildirilmektedir [1,13,19]. Plazma folatının %30-40'ı başta albumin olmak üzere düşük afiniteli bağlayıcı proteinlere (K d folat ~1 mM) bağlıdır.…”

Falsely elevated C4‐carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening

“…Folate plasma level was normal (13 ng/ml; n.v. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. At the age of 5 months, the child showed a mild persistent axial hypotonia and a mild hypertonia of legs.…”