Histidine synthesis, rate

Negative repression was investigated in the tryptophan (trp) synthesis operons of E. coli and Salmonella typhimurium, and the histidine synthesis operon of Salmonella. The trp operon is totally derepressed in the presence of nonsurplus amounts of tryptophan. Here, transcription and translation go at maximal rates. Enzymes of the tryptophan system synthesized it in amounts which are totally utilized during translation. This condition is known as turn on. The activity of the first enzyme in the sequence of tryptophan synthesis — anthranilate synthetase — is inhibited within several seconds after the addition of surplus tryptophan. The aporepressor becomes the repressor and inhibits transcription of the operon (negative repression) after it associates with the effector, tryptophan. This association occurs if the surplus of tryptophan exists for a sufficient amount of time. After several minutes, most of the resulting mRNA is degraded and the rate of synthesis is noticeably reduced (known as the turn of condition). 

There are two distinct pools of HA in the brain (1) the neuronal pool and (2) the non-neuronal pool, mainly contributed by the mast cells. The turnover of HA in mast cells is slower than in neurons it is believed that the HA contribution from the mast cells is limited and that almost all brain histaminergic actions are the result of HA released by neurons (Haas Panula, 2003). The blood-brain barrier is impermeable to HA. HA in the brain is formed from L-histidine, an essential amino acid. HA synthesis occurs in two steps (1) neuronal uptake of L-histidine by L-amino acid transporters and (2) subsequent decarboxylation of l-histidine by a specific enzyme, L-histidine decarboxylase (E.C. 4.1.1.22). It appears that the availability of L-histidine is the rate-limiting step for the synthesis of HA. The enzyme HDC is selective for L-histidine and its activity displays circadian fluctuations (Orr Quay, 1975). HA synthesis can be reduced by inhibition of the enzyme HDC. a-Fluoromethylhistidine (a-FMH) is an irreversible and a highly selective inhibitor of HDC a single systemic injection of a-FMH (10-50 mg/kg) can produce up to 90% inhibition of HDC activity within 60-120 min (Monti, 1993). Once synthesized, HA is taken up into vesicles by the vesicular monoamine transporter and is stored until released. 

There are several types of -class CAs i.e., a-CA I-VII, reported in the literature, out of which the human carbonic anhydrase II (HCA II), the most extensively studied carbonic anhydrase, has an exceptionally high CO2 hydration rate and a wide tissue distribution 107). The HCA II comprises a single polypeptide chain with a molecular mass of 29.3 kDa and contains one catalytic zinc ion, coordinated to three histidine residues, His 94, His 96, and His 119. A tetrahedral coordination geometry around the metal center is completed with a water molecule, which forms a hydroxide ion with a pK value of 7.0 108). Quigley and co-workers 109,110) reported that the inhibition of the synthesis of HCO3 from CO2 and OH- reduces aqueous humor formation and lowers intra-ocular pressure, which is a major risk factor for primary open-angle glaucoma. 

Humans have no dietary requirement for protein, per se, but, the protein in food does provide essential amino acids (see Figure 20.2, p. 260). Ten of the twenty amino acids needed for the synthesis of body proteins are essential—that is, they cannot be synthesized in humans at an adequate rate. Of these ten, eight are essential at all times, whereas two (arginine and histidine) are required only during periods of rapid tissue growth characteristic of childhood or recovery from illness. 

High concentrations of blood phenylalanine result in increased uptake of phenylalanine into the brain and concomitant dcCTease in the uptake of other large neutral amino adds (LNAA). Phenylalanine is transported into the brain by one of the LNAA carriers, the 1. -amino add transporter 1 (LAT-1) [45 8]. This transporter also selectively transports the amino adds valine, isoleucine, methionine, threonine, tryptophan, tyrosine, and histidine. The binding of the LNAA to the LAT-1 transporter is a competitive process the rate of transport is proportionate to the blood concentration of all the transported amino acids [49]. This system has the highest affinity for phenylalanine, which in case of its high concentration in the blood, significantly decreases the transport of other LNAA and more phenylalanine is transported into the brain. By influence on the activity of tyrosine and tryptophan hydroxylases, elevated brain phenylalanine concentrations also negatively impact the synthesis of catecholamines and serotonin in the brain due to the altered metabolism of tyrosine and tryptophan [4]. 

As a possible explanation for the unequal rates of synthesis of various hemoglobins which are controlled by multiple alleles in heterozygous individuals, Itano [9] suggested that a mutation which results in the alteration of the structure of hemoglobin may also alter its net rate of synthesis. The modulation hypothesis, introduced by Ames andHartman [10] to explain the polarity effect in the synthesis of the histidine biosynthetic enzymes, stems from a similar consideration. The hypothesis... 

Presence or absence of external histidine is not the only factor regulating the rate of histidine biosynthesis. The bacterium also keeps its rate of synthesis of the amino acid in line with its growth rate. Clearly, a bacterium growing with a 60-minute generation time needs to produce histidine at only half the rate of a bacterium growing with a 30-minute... 

The aromatic biosynthetic pathways do not exist in isolation. Some interactions among the branches of the common aromatic pathway have been mentioned in this chapter. Substrates which are common to several different pathways can serve to interconnect the functioning of the pathways, although they may appear to be quite independent. Jensen has coined the term metabolic interlock to describe regulatory interactions among different metabolic pathways [146a,243,244]. A number of reports have appeared of interactions between the histidine and tryptophan pathways in B. subtilis involving effects on the rates of enzyme synthesis [245,246] as well as enzyme activity [244], Evidence for an interaction between the histidine and tryptophan pathways of N. crassa has also been reported [247],... 

The observations on the histidine operons described above clearly show that all the enzymes with amino acid sequences determined by the histidine operon are not synthesized in equimolecular amounts. But the rate at which each of the proteins is synthesized is determined by the position of the cistron within the operon. The amount of protein synthesized decreases the further the cistron is from the operator gene. Furthermore, mutations that interfere with the biosynthesis of one enzyme of the histidine pathway lead to a reduction of the rate of synthesis of all the enzymes with structures dictated by cistrons distal to the mutated cistron. 

Histamine production. Growing cultures of P. acnes produce histamine (Allaker et al., 1986) and its synthesis increases with increasing growth rate. The growth of P. acnes is optimal at pH 6.0, while histamine synthesis has two pH-optima of 4.5 and 7.5. Histamine is formed as a result of histidine decarboxylation. 

L-Histidine inhibits the rate of synthesis of compound III and as a consequence, of aminoribosylimidazolecarboxamide phosphate. Glutamine is essential for the conversion of compound III to the latter and it will stimulate this conversion even in the presence of histidine. 

Due to their rate of synthesis within the body, ARG and histidine are considered semi-essential AAs. It appears that these AAs cannot be synthesized by the body at a rate that will support growth (especially in children). 

Another facility offered by BOP is the possibility to couple DOHA salts, due to the high rate ratio of amino acid coupling towards dicyclohexylamine (DCHA). This feature is especially useful in SPPS where the small amount of dicyclohexylamide formed is easily washed out. The main application of that procedure lies in the introduction of histidine as the cheap and easily acessible Boc-His(Boc)-OH both in liquid (eq 6) and solid " phase synthesis. 

Reymond et al. report the synthesis of peptide dendrimers displaying multiple serine-histidine (diad) residues to catalyze ester hydrolysis reactions [33], Best results where obtained with the fourth generation dendrimer 36. The rate acceleration of the hydrolysis of a fluorescent nonanoyl ester (35) was 140,000-fold more efficient than with 4-melhyl-imidazole as reference catalyst (Scheme 7.7). 

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