Biologically active form

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... 

Hori, K., and Cormier, M. J. (1972). Structure and chemical synthesis of a biologically active form of Renilla (sea pansy) luciferin. Proc. Natl. Acad. Sci. USA 70 120-123. 

Summary term for a number of steroid hormones and their precursors with differentiation-inducing activity in many tissues. As regards bone, three components are relevant cholecalciferol ( vitamin D ) 25-hydroxyvi-taminD3 (calcidiol) and 1,25-dihydroxy vitamin D3 (calcitriol). The latter is the biologically active form and increases both intestinal calcium absoiption and bone resorption. Vitamin D preparations are widely used for the treatment of osteoporosis. Daily supplementation with vitamin D reduces bone loss in postmenopausal women and hip fractures in elderly subjects. 

Once the blood glucose values in the treated animals had returned to the high, diabetic levels, a second injection of insuUn-containing microspheres again reduced these levels to normal for about 5 more days. It is therefore possible to incorporate labile biological products into the polyanhydrides and to release them in a biologically active form. At the same time, this release can be sustained over a period of time in a controlled fashion. 

In plants and, consequently, in soy food products, isoflavones occur in three main biologically active forms ... 

Myo-inositol is one of the most biologically active forms of inositol. It exists in several isomeric forms, the most common being the constituent of phospholipids in biological cell membranes. It also occurs as free inositol and as inositol hexaphosphate (IP6) also known as phytate which is a major source from food. Rice bran is one of the richest sources of IP6 as well as free inositol. Inositol is considered to belong to the B-complex vitamins. It is released in the gastrointestinal tract of humans and animals by the dephosphorylation of IP6 (phytate) by the intestinal enzyme phytase. Phytase also releases intermediate products as inositol triphosphate and inositol pentaphosphate. Inositol triphosphate in cellular membrane functions as an important intra- and intercellular messenger, that merits its value as a nutritional therapy for cancer. 

The native, biologically active form of a protein molecule is held together by a delicate balance of noncovalent forces hydrophobic, ionic, van der Waals interactions, and hydrogen bonds. In addition,... 

It soon became apparent that the biologically active forms of Vitamin Bj.2 contained the unique Co—C-a-bond, and the instability of these covalent compounds to visible light facilitated observations on the occurrence of functional corrinoids in a number of enzymes. Deoxyadenosyl-cobalamin was found to be the most abundant corrinoid in bacteria (24) and in mammalian liver (25). Methylcobalamin was found in Escherichia coli (26), calf liver and human blood plasma (27), and also in a number of Clostridia (28). 

Following the elucidation of the structure of the biologically active forms of Vitamin B12 in 1961, a number of enzymes have been well characterized which require B 12-coenzymes. A survey of the properties of these enzymes in terms of molecular weight, subunits and other co-factor requirements has already been published in excellent reviews by Hogenkamp (29) and Stadtman (30). 

When the concentration of the free form of a hormone decreases, then more of this hormone will be released from the binding proteins. The free hormone is the biologically active form. It binds to the target tissue to cause its actions and is involved with the negative feedback control of its secretion. The binding of hormones to plasma proteins has several beneficial effects, including ... 

Gel-filtration analysis reveals bands of molecular mass 40-70 kDa. These represent dimers (and some multimers) of the IFN-y polypeptide. Its biologically active form appears to be a homodimer in which the two subunits are associated in an antiparallel manner. 

The biologically active form of M-CSF is a homodimer (two identical subunits). These homodimers can exist as integral cell surface proteins, or may be released from their producer cell by proteolytic cleavage, thus yielding the soluble cytokine. The M-CSF receptor is a single-chain, heavily glycosylated, polypeptide of molecular mass 150 kDa. 

Because T3 (and not T4) is the biologically active form, levothyroxine administration results in a pool of thyroid hormone that is readily and consistently converted to T3. 

Organisms may be considered susceptible if the Minimum Inhibitory Concentration (MIC) is not more than 4.0 yg/ml and intermediate if the MIC is 4.0-12.5 yg/ml (see Table 1). Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations and in a biologically active form. 

Similar metabolites were found produced by man (19)(20)(21)t monkeys( ), dogs (8), chickens(22)> calves(23) and microorganisms(4). The ratios of these metabolites, however, were found to vary with the individual. The overall conversion of nalidixic acid to hydroxynalidixic acid had been reported by McChesney(S) to be normally about 32% bicarbonate supplementation increased this to about 40%. Bicarbonate supplementation also increased the amount of total naphthyridine excreted in the biologically active form. 

Examples Infrared spectroscopy is employed to compare samples of chloramphenicol palmitate (biologically active form) recovered from chloramphenicol palmitate mixture vis-a-vis an artificially prepared mixture of authentic sample consisting 10 per cent of the inactive polymorph . 

In addition to the protein and low-molecular-weight thiols that react with PAN, there are several other reactive biochemicals. Reduced nicotinamide derivatives are susceptible to oxidation by PAN (at 72 ppm for 1-5 min), whereas the oxidized forms are resistant. The capability of PAN to oxidize these compounds rapidly dissipates in aqueous solution, with a half-life of 4-10 min, depending on pH. The oxidation products appear to be the biologically active forms of the nicotinamide derivatives. Purines and pyrimidines react with PAN (at 1,000 ppm for 30-120 min). The order of sensitivity is thymine, guanine, uracil, cytosine, and adenine. Their reactions were studied at relatively low pH and at high PAN concentration and are probably not of biologic significance. 

The enzymatic conversion of many analogues of the naturally occurring purines directly to their biologically active form, the ribonucleotides, in vivo [5, 8, 10, 13, 39] underlines the importance of these enzymes to the drug action of this class of compounds. 2-Aminoadenine (2, 6-diaminopurine, I) [107], 2-fluoroadenine (II) [108], 4-aminopyrazolo [3, 4-d] pyrimidine (VIll) [109]. and 2- and 8-aza-adenine (IX and X) [ 110, 111] have all been shown to be substrates for the adenine phosphoribosyltransferase [J12, 113]. Extensive studies on the metabolism of 2-aminoadenine (I) in E. coli [114, 115], L cells [116], and mice [117] have also shown its conversion by this enzyme to the ribonucleotide. 

In nature, the biologically active form of acetic acid is acetyl-coenzyme A (acetyl-CoA) (see Box 7.18). Two molecules of acetyl-CoA may combine in a Claisen-type reaction to produce acetoacetyl-CoA, the biochemical equivalent of ethyl acetoacetate. This reaction features as the start of the sequence to mevalonic acid (MVA), the precursor in animals of the sterol cholesterol. Later, we shall see another variant of this reaction that employs malonyl-CoA as the nucleophile (see Box 10.17). 

Soluble proteins have a more complex structure than the fibrous, completely insoluble structural proteins. The shape of soluble proteins is more or less spherical (globular). In their biologically active form, globular proteins have a defined spatial structure (the native conformation). If this structure is destroyed (denaturation see p. 74), not only does the biological effect disappear, but the protein also usually precipitates in insoluble form. This happens, for example, when eggs are boiled the proteins dissolved in the egg white are denatured by the heat and produce the solid egg white. 

Total Synthesis of the Biologically Active Form of A -Acetylneuraminic Acid... 

DANISHEFSKY AND DeNINNO Biologically Active Form of NeuSAc... 

Metabolism/Excretion — Amphotericin B has a relatively short initial serum half-life of 24 hours, followed by a second elimination phase with a half-life of approximately 15 days. The drug is slowly excreted by the kidneys with 2% to 5% as the biologically active form. 

Table 7.10. Biochemical characteristic of the neurotrophin family of neurotrophic factors. Except for NT-6, the molecular masses quoted are those of the homodimeric structure, which represents their biologically active forms. See text for further details...

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