Physiological conditions reactions under

Amines like ammonia are weak bases They are however the strongest uncharged bases found m significant quantities under physiological conditions Amines are usually the bases involved m biological acid-base reactions they are often the nucleophiles m biological nucleophilic substitutions... 

Carbohydrates undergo a number of isomerization and degradation reactions under both laboratory and physiological conditions For example a mixture of glucose fructose and mannose results when any one of them is treated with aqueous base This reaction can be understood by examining the consequences of enohzation of glucose... 

This theory has stimulated activity in two main directions, suggestions for changes in detail in the steps of processes for particular alkaloids, and work on laboratory syntheses of known alkaloids, using the reactions specified and operated under conditions which might obtain in a plant, i.e., under what are now described as physiological conditions. All the results indicate that the theory is well-founded, and it seems possible that a technique may eventually be found by which the process may be observed in operation, direetly or indirectly, in situ, say in a solanaceous plant. 

The first step in this study has involved experiments which synthesize alkaloids in vitro under quasi-cellular conditions, using reactions which can proceed in the living cell and compounds which actually occur in the cell or which are supposed to be intermediates in the plant metabolism. Such synthesesaredesignatedassyntheses under physiological conditions. ... 

A characteristic of all the above reactions is that the yield of the aldoliza-tion product depends on the pH of the reaction mixture (324), the maximum yield usually occurring near pH 7. Such reactions have been carried out in vitro in dilute aqueous buffer under so-called physiological conditions, i.e., conditions attainable in the living cell. Although this oversimplified technique for the study of alkaloid biogenesis is now being abandoned in favor of experiments in vivo with labeled precursors, such reactions are still of interest to organic chemists. 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

The hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate (Eigure 23.7), like all phosphate ester hydrolyses, is a thermodynamically favorable (exergonic) reaction under standard-state conditions (AG° = —16.7 kj/mol). Under physiological conditions in the liver, the reaction is also exergonic (AG = —8.6 kJ/mol). Fructose-1,6-bisphosphatase is an allosterically regulated enzyme. Citrate stimulates bisphosphatase activity, hut fructose-2,6-bisphosphate is a potent allosteric inhibitor. / MP also inhibits the bisphosphatase the inhibition by / MP is enhanced by fructose-2,6-bisphosphate. 

A few other aldehydes have been used in the reaction, either under normal or pseudo-physiological conditions. Of these, glycolalde-hyde, 5-hydroxypentanal, phenylacetaldehyde, and benzalde-hyde condense readily, but hydroxy and methoxy derivatives of these aromatic aldehydes give the product in poor yield,presumably due to their instability, as evidenced by their tendency to undergo self-condensation in acid solution. Reaction with phthaldehydic acids, such as opianic acid, proceeded readily, whereas reaction with chloral did not occur,... 

The second line of circumstantial evidence quoted in support of this hypothesis is the ready formation of l,2,3,4-tetrahydro-/3-carboline derivatives under pseudo-physiological conditions of temperature, pH, and concentration. Tryptamine and aldehydes, trypt-amine and a-keto acids, and tryptophan and aldehydes condense at room temperature in a Pictet-Spengler type intramolecular Mannich reaction in the pH range 5.2-8.0 (cf. Section III, A, 1, a). It was argued that experiments of this type serve as models for biochemical reactions and may be used in evidence. 

The Mannich reactions plays an important role in pharmaceutical chemistry. Many /3-aminoalcohols show pharmacological activity. The Mannich reaction can take place under physiological conditions (with respect to pH, temperature, aqueous solution), and therefore can be used in a biomimetic synthesis e.g. in the synthesis of alkaloids. 

In this type of reaction an antigen elicits the generation of cytotoxic T-lymphocytes ( immune defense). Cytotoxic T-lymphocytes (Tc) destroy antigen bearing cells by inducing apoptosis. This reaction can be viewed as the cellular counterpart to the humoral Type II reactions. They play an important physiological role in the defense of viruses, and can become allergic reactions under the same conditions as described for Type II reactions. 

Unidirectional arrows are also used to describe reactions in living cells where the products of reaction (2) are immediately consumed by a subsequent enzyme-catalyzed reaction. The rapid removal of product P or Q therefore precludes occurrence of the reverse reaction, rendering equation (2) functionally irreversible under physiologic conditions. 

The ph osphorylation of glucose to glucose 6-phos-phate, the first reaction of glycolysis (Figure 17-2), is highly endergonic and cannot proceed under physiologic conditions. 

When (1) and (2) are coupled in a reaction catalyzed by hexokinase, phosphorylation of glucose readily proceeds in a highly exergonic reaction that under physiologic conditions is irreversible. Many activation reactions follow this pattern. 

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

Gases that participate in chemical reactions typically are at pressures different from one bar. Substances in solution are likely to be at concentrations different from one molar. For example, a biochemist who wants to know what processes are spontaneous under physiological conditions will find that the substances dissolved in biological fluids are rarely at one molar concentration. How does AG vary with changes in molarity and pressure Recall that enthalpy is virtually independent of concentration but that entropy obeys Equation ... 

Not all oxidants formed biolc cally have the potential to promote lipid peroxidation. The free radicals superoxide and nitric oxide [or endothelium-derived relaxing aor (EDRF)] are known to be formed in ww but are not able to initiate the peroxidation of lipids (Moncada et tU., 1991). The protonated form of the superoxide radical, the hydroperoxy radical, is capable of initiating lipid peroxidation but its low pili of 4.5 effectively precludes a major contribution under most physiological conditions, although this has been suggested (Aikens and Dix, 1991). Interestingly, the reaction product between nitric oxide and superoxide forms the powerful oxidant peroxynitrite (Equation 2.6) at a rate that is essentially difiiision controlled (Beckman eta/., 1990 Huie and Padmaja, 1993). 

The abasic sites (3, Scheme 8.2) resulting from the loss of alkylated bases from DNA are both cytotoxic and mutagenic. " The cyclic acetal (3) exists in equilibrium with small amounts (—1%) of the open chain aldehyde (4). The acidic nature of a-proton in the aldehyde form of the abasic lesion facilitates 3-elimination of the 3 -phosphate residue to yield a strand break. " This reaction occurs with a half-life of about 200 h under physiological conditions (pH 7.4, 37°C), but can be accelerated by heat, basic conditions, or the presence of various amines. " ... 

Deamination, the hydrolytic loss of exocyclic amino groups on the DNA bases, is typically a very slow reaction. For example, deamination of cytosine residues in dnplex DNA occnrs with a half-life of about 30,000 years under physiological conditions, and the deamination of adenine residues is still more sluggish. " Alkylation at the N3-position of cytosine (Scheme 8.5) greatly increases the rate of deamination (ty2 = 406 h). Deamination of 3-methyl-2 -deoxycytidine proceeds 4000 times faster than the same reaction in the unalkylated nucleoside. Alkylation of the N3-position in cytosine residues also facilitates deglycosylation (Jy2 = 7700 h, lower pathway in Scheme 8.5), but the deamination reaction is 20 times faster and, therefore, predominates. ... 

---