Regulation-by-feedback

The carotenoid pathway may also be regulated by feedback inhibition from the end products. Inhibition of lycopene cyclisation in leaves of tomato causes increase in the expression of Pds and Psy-1 (Giuliano et al, 1993 Corona et al, 1996). This hypothesis is supported by other studies using carotenoid biosynthesis inhibitors where treated photosynthetic tissues accumulated higher concentrations of carotenoids than untreated tissues (reviewed by Bramley, 1993). The mechanism of this regulation is unknown. A contrary view, however, comes from studies on the phytoene-accumulating immutans mutant of Arabidopsis, where there is no feedback inhibition of phytoene desaturase gene expression (Wetzel and Rodermel, 1998). 

In addition to these two subtypes, there is also evidence that the release of dopamine is partially regulated by feedback inhibition operating via the dopamine autoreceptor. 

The biosynthesis of the purines is also regulated by feedback inhibition. ADP and GDP inhibit the formation of PRRPP from ri-bose-5 -phosphate. Similarly, step 2a is inhibited by AMP and GMP. 

Purine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition... 

As indicated in Fig. 24-17, pyruvate is the starting material for the formation of both l- and D-alanine and also the branched chain amino acids valine, leucine, and isoleucine.339,340 The chemistry of the reactions has been discussed in the sections indicated in the figure. The first step is catalyzed by the thiamin diphosphate-dependent acetohydroxyacid synthase (acetolactate synthase), which joins two molecules of pyruvate or one of pyruvate and one of 2-oxobutyrate (Fig. 24-17 Fig. 14-3).340a b In E. coli there are two isoenzymes encoded by genes ilv B and ilv HI. Both are regulated by feedback inhibition by valine, probably... 

Urea and creatinine elevations in plasma are in general not sensitive enough to detect low-level alterations (less than 75 % loss) in functional nephron mass, due to the contribution of renal secretion and/or reabsorption to their overall excretion, (which can compensate for their decreased filtration), to wide variations in baseline levels of some analytes, and to inherent imprecision in the assays used (Finn and Porter 1998 Price 2002 Starr et al. 2002 Shemesh et al. 1985). In particular, urea will underestimate GFR (due to extensive tubular reabsorption with decreased GFR) (Baum et al. 1975 Kaplan and Kohn 1992 Newman and Price 1999). Creatinine tends to overestimate GFR because it is secreted by the tubule in many species and secretion increases with reduced GFR (Shemesh et al. 1985 Andreev et al. 1999 Newman and Price 1999 Starr et al. 2002). In addition, creatinine synthesis is regulated by feedback inhibition which limits the degree of elevation than can occur in plasma with renal injury (Watson et al. 2002). 

Fig. 2 Metabolic pathways in C. glutamicum for biosynthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine (a) and amino acids belonging to the aspartate family including lysine, methionine, threonine, and isoleucine (b). Metabolic regulation by feedback inhibition is indicated by dotted lines...

Most of the pathways of amino acid biosynthesis are regulated by feedback inhibition, in which the committed step is allosterically inhibited by the final product. Branched pathways require extensive interaction among the branches that includes both negative and positive regulation. The regulation of glutamine synthetase from if. coli is a striking demonstration of cumulative feedback inhibition and of control by a cascade of reversible covalent modifications. 

Nucleotide biosynthesis is regulated by feedback inhibition in a manner similar to the regulation of amino acid biosynthesis (Section 24,3). Indeed, aspartate transcarbamoylase, one of the key enzymes for the regulation of pyrimidine biosynthesis in bacteria, was described in detail in Chapter 10. Recall ihaiATCase is inhibited by CTP, the final product ofpyrimidine biosynthesis, and stimulated by ATP. Carbamoyl phosphate synthetase is a site of feedback inhibition in both prokaryotes and eukaryotes. 

Xucleotide biosynthesis is regulated by feedback inhibition in a manner. similar to the regulation of amino acid biosynthesis (Section 24.3). These regulatory pathways ensure that the various nucieotidcs are produced in the required quantities. 

The precursor of cysteine is the amino acid serine. The biosyntiiesis of this amino acid is mainly regulated by feedback-inhibition. The enzyme, which is sensitive to higher serine concentrations in the cell is the 3-phosphoglycerate dehydrogenase. The serA, coding for this enzyme, was subjected to a mutagenesis procedure to obtain mutants with a reduced feedback inhibition but... 

The components of the hypothalamie-pituitary-thyroid axis are outlined in Figure 2. TRH, a tripeptide, is secreted by the hypothalamus and in turn causes the synthesis of a large glycoprotein hormone. TSH. from the anterior pituitary. This drives the synthesis of thyroid hormones by the thyroid. Production of TSH is regulated by feedback from circulating unbound thyroid hormones. A knowledge of these basics is essential for the correct interpretation of results in the investigation of thyroid disease. Remember ... 

---