Rate of synthesis

Hydrolysis of esters and amides by enzymes that form acyl enzyme intermediates is similar in mechanism but different in rate-limiting steps. Whereas formation of the acyl enzyme intermediate is a rate-limiting step for amide hydrolysis, it is the deacylation step that determines the rate of ester hydrolysis. This difference allows elimination of the undesirable amidase activity that is responsible for secondary hydrolysis without affecting the rate of synthesis. Addition of an appropriate cosolvent such as acetonitrile, DMF, or dioxane can selectively eliminate undesirable amidase activity (128). 

The responsiveness of a tissue to a hormone depends on the density of receptors within its component cells. The number of receptors is determined by their rate of synthesis and catabolism, which is itself controlled by complex feedback mechanisms involving hormone action. Some chemicals are known to interfere with this regulation. For example, TCDD can act to increase or decrease the expression of the oestrogen receptor. ... 

The Temkin-Pyzhev equation deseribes the net rate of synthesis over promoted iron eatalyst as ... 

Although mast cells and basophils probably account for >90% of stored histamine in the body, histamine is also present in platelets, enterochromaffin-like cells, endothelial cells, and neurons. Histamine can act as a neurotransmitter in the brain. Histaminergic nerves have their cell bodies within a very small area of the brain (the magnocellular nuclei of the posterior hypothalamus) but have axons in most areas of the forebrain. There is also evidence for axons projecting into the spinal (Fig. 1) cord. Finally, there is evidence that histamine synthesis can be induced in tissues undergoing rapid tissue growth and repair. In certain neonatal tissues (e.g. liver), the rate of synthesis of this unstored diffusable histamine (termed nascent histamine) is profound and may point to a role for histamine is cell proliferation. 

The rate of synthesis is similar for trace amines and monoamine neurotransmitters, however, trace amines undergo a more rapid turnover due to their higher affinity to MAO and the lack of comparable cellular storage. Thus, the tissue concentration of trace amines in the vertebrate central nervous system is estimated to be in the range of 1-100 nM, depending on the trace amine and brain area, in contrast to micromolar concentrations of classic monoamine neurotransmitters. 

The significance of these metabolites in the biosynthesis of the thiamine thiazole in considered next. Although, from their constitution, and from the tracer experiments, the metabolites are undoubtedly the products of transformation of 1-deoxy-D-t/ireo-pentulose, their significance in the biosynthesis of the thiazole of thiamine is not clear. The thiazole glycol is not a product arising from a transformation of the thiazole (5) of thiamine. Reduction to this thiazole (5) occurs in dialyzed extracts of disrupted cells, in the presence of ATP, NADH, and NADPH, but only at 0.2% the rate of synthesis of the thiamine thiazole (5) by intact cells. The behavior of the thiazole glycol on plates is merely a consequence of the extreme sensitivity of the tetrazolium reagent. 

Induction With reference to enzymes an increase in activity due to an increase in their cellular concentrations. This may be a response to a xenobiotic, and often involves an increased rate of synthesis of the enzyme. 

Long-chain fatty acid synthesis is controlled in the short term by allosteric and covalent modification of euTymes and in the long term by changes in gene expression governing rates of synthesis of enzymes. 

Under normal feeding patterns the rate of tissue protein catabolism is more or less constant throughout the day it is only in cachexia that there is an increased rate of protein catabolism. There is net protein catabolism in the postabsorptive phase of the feeding cycle and net protein synthesis in the absorptive phase, when the rate of synthesis increases by about 20-25%. The increased rate of protein synthesis is, again, a response to insulin action. Protein synthesis is an energy-expensive process, accounting for up to almost 20% of energy expenditure in the fed state, when there is an ample supply of amino acids from the diet, but under 9% in the starved state. 

The activity of carbamoyl phosphate synthase I is determined by A -acetylglutamate, whose steady-state level is dictated by its rate of synthesis from acetyl-CoA and glutamate and its rate of hydrolysis to acetate and glutamate. These reactions are catalyzed by A -acetylglu-tamate synthase and A -acetylglutamate hydrolase, respectively. Major changes in diet can increase the concentrations of individual urea cycle enzymes 10-fold to 20-fold. Starvation, for example, elevates enzyme levels, presumably to cope with the increased production... 

ALASl. This repression-derepression mechanism is depicted diagrammatically in Figure 32-9. Thus, the rate of synthesis of ALASl increases greatly in the absence of heme and is diminished in its ptesence. The turnover rate of ALASl in rat liver is normally rapid (half-life about 1 hour), a common feature of an enzyme catalyzing a rate-limiting reaction. Heme also affects translation of the enzyme and its transfer from the cytosol to the mitochondrion. 

Since biosynthesis of IMP consumes glycine, glutamine, tetrahydrofolate derivatives, aspartate, and ATP, it is advantageous to regulate purine biosynthesis. The major determinant of the rate of de novo purine nucleotide biosynthesis is the concentration of PRPP, whose pool size depends on its rates of synthesis, utilization, and degradation. The rate of PRPP synthesis depends on the availabihty of ribose 5-phosphate and on the activity of PRPP synthase, an enzyme sensitive to feedback inhibition by AMP, ADP, GMP, and GDP. 

Changes in the quantities of the various normal hemoglobin components during developmental stages can be explained in terms of ill-defined regulatory mechanisms which control the rate of synthesis of the polypeptide chains. Such mechanisms have to... 

One limitation of this method is that the specific activity of the radiolabel is progressively diluted as the radiolabelled transmitter is released from neurons and replaced by that derived from unlabelled substrate. This method also assumes that there is no compartmentalisation of the terminal stores, yet there is ample evidence that newly synthesised acetylcholine and monoamines are preferentially released. An alternative approach is to monitor the rate at which the store of neurotransmitter is depleted after inhibition of its synthesis (Fig. 4.1). However, the rate of release of some neurotransmitters (e.g. 5-HT) is partly governed by their rate of synthesis and blocking synthesis blunts release. 

At steady-state there is no net loss of transmitter from the system and so the rate of synthesis of transmitter equals the rate of its efflux. Thus ... 

The reaction of choline with mitochondrial bound acetylcoenzyme A is catalysed by the cytoplasmic enzyme choline acetyltransferase (ChAT) (see Fig. 6.1). ChAT itelf is synthesised in the rough endoplasmic reticulum of the cell body and transported to the axon terminal. Although the precise location of the synthesis of ACh is uncertain most of that formed is stored in vesicles. It appears that while ChAT is not saturated with either acetyl-CoA or choline its synthesising activity is limited by the actual availability of choline, i.e. its uptake into the nerve terminal. No inhibitors of ChAT itself have been developed but the rate of synthesis of ACh can, however, be inhibited by drugs like hemicholinium or triethylcholine, which compete for choline uptake into the nerve. 

Figure 22.1 Pathways projecting to and from the suprachiasmatic nucleus (SCN). Inputs from photoreceptors in the retina help to reset the circadian clock in response to changes in the light cycle. Other inputs derive from the lateral geniculate complex and the serotonergic, Raphe nuclei and help to reset the SCN in response to non-photic stimuli. Neurons in the SCN project to the hypothalamus, which has a key role in the regulation of the reproductive cycle, mood and the sleep-waking cycle. These neurons also project to the pineal gland which shows rhythmic changes in the rate of synthesis and release of the hormone, melatonin...

Both enzymes have been continuously in the limelight of interest, as attested by thousands of reports and dozens of recent review articles on their structure and mechanism of action. Less is known about the regulation of the activity of the two enzymes under physiological conditions [2,3,35-38] and about the control of their rate of synthesis and degradation that adjusts their concentration to the physiological requirements [39-41]. 

Most of the permeases which are insensitive to NCR are synthesized in cells grown on minimal medium containing ammonium ions, without addition of any inducer. However, a few of them do appear to be inducible. For instance, addition to the medium of methionine, leucine valine, isoleucine and alanine, which are taken up by several distinct NCR-insensitive permeases, increases the rate of synthesis of the corresponding permeases [54]. This process involves amplification of a basal rate of permease synthesis rather than all-or-none induction. It has not been studied further at the molecular level. 

Nasmyth Cln3 is a transcriptional activator of the Clnl and Cln2 cyclins, which are somewhat similar to cyclin E. It is a very unstable protein whose rate of synthesis is proportional to cell size. Its concentration is going to be directly and immediately proportional to the rate of synthesis. This stuff goes into the nucleus, which is roughly constant in size. 

Earlier studies showed that reactions of sugars with ammonia lead to small molecules such as amines or organic acids. A. L. Weber has reported important autocatalytic processes occurring when trioses are allowed to react with ammonia under anaerobic conditions, such reactions provide products which are autocatalyt-ically active. Their autocatalytic activity was determined directly by investigating their effect on an identical triose-ammonia reaction. Both an increase in the triose degradation rate and an increased rate of synthesis of pyruvate, the dehydration product of the triose, were observed. Such processes may have been of importance for prebiotic chemistry occurring on the primeval Earth (Weber, 2007). 

In summary, certain equilibrium constants of complex formation, of solubility products and of redox potentials form a set of fixed values that must be looked at in the context of the compartment which contains the components and which controlled evolution in fair part, against a background of rising amounts of environmental oxidised elements. The other factors were the rates of synthesis as dictated by supply of energy and of reactants in the environment. 

Apolipoprotein AI (apoAI) is the major apolipoprotein of HDL and plays an important role in the formation of mature HDL and the reverse cholesterol transport. HDL concentrations are largely determined by the rate of synthesis of apoAI in the liver. As a consequence deficiency of apoAI results in an almost complete absence of HDL and in accelerated atherosclerosis. In the promoter of the apoAI... 

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