Metabolic and Anti-inflammatory Properties of 6-Methyl Prednisolone Alone and in Combination with Anabolic Hormones

Bavetta, Lucien A.; Bekhor, Isaac; Shah, Rajni; O'Day, Pat; Nimni, M. E.

doi:10.1210/endo-71-2-221

Cited by 13 publications

(2 citation statements)

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“…A rough etidoplasmic reticulum is usually assoeiated with cells which are actively synthesizing proteins for export (Ross 1968). Adrenalcorticoid hormones have been shown to inhibit the biosynthesis of collagen as well as other proteins (Bavetta et al 1962, Nimni & Bavetta 1964. The biochemical block tnay lie at the level of the m-RNA-r-RNA* cotnplex sinee steroids cause a reduction in the total amount of particulate RNA (Gabourel & Fox 1965).…”

Section: Ribosotnal Evetitsmentioning

confidence: 99%

Metabolic pathways and control mechanisms involved in the biosynthesis and turnover of collagen in normal and pathological connective tissues

Nimni¹

1973

J Oral Pathology Medicine

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Abstract. The biosynthesis of collagen molecules and their subsequent assembly into fibers involves a complex series of post‐ribosomal modifications which occur intracellularly and extracellularly. Some of these subtle alterations lead to the formation of intramolecular and intermolecular cross‐links, whereas others seem to dictate the 3‐dimensional organization of the collagen fibers. For their normal function, tissues require an optimum amount of collagen and proteoglycans. Such a balance coupled with specificity built into collagen seems to assure adequate function. Changes in the rates of synthesis, turnover or transcription of genetic information which affect the type of collagen deposited at a particular site may lead lo a stale of disease. It is hoped that our current understanding of such mechanisms, coupled with our ability to inhibit or accelerate some of these processes, will allow us lo effectively control the metabolism of connective tissues.

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Section: Ribosotnal Evetitsmentioning

confidence: 99%

Metabolic pathways and control mechanisms involved in the biosynthesis and turnover of collagen in normal and pathological connective tissues

Nimni¹

1973

J Oral Pathology Medicine

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“…This can be illustrated particularly well using the example of the synthetic glucocorticoid methylprednisolone, which exhibits reduced MR affinity and multiplied glucocorticoid potency compared with its unmethylated derivative, prednisolone. Methylprednisolone, also known as medrol, is applied for the treatment of arthritis and other inflammatory diseases and thus, highly appreciated by the pharmaceutical industry (Bavetta, Bekhor, Shah, O'Day, & Nimni, ). The increasing demand of this compound requires the development of production strategies, that are aimed at achieving high‐product yields while maintaining the cost‐effectiveness of the process.…”

Section: Introductionmentioning

confidence: 99%

Identification and circumvention of bottlenecks in CYP21A2‐mediated premedrol production using recombinant Escherichia coli

König

Brixius‐Anderko

Milhim

et al. 2019

Biotech & Bioengineering

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Synthetic glucocorticoids such as methylprednisolone are compounds of fundamental interest to the pharmaceutical industry as their modifications within the sterane scaffold lead to higher inflammatory potency and reduced side effects compared with their parent compound cortisol. In methylprednisolone production, the complex chemical hydroxylation of its precursor medrane in position C21 exhibits poor stereo‐ and regioselectivity making the process unprofitable and unsustainable. By contrast, the use of a recombinant E. coli system has recently shown high suitability and efficiency. In this study, we aim to overcome limitations in this biotechnological medrane conversion yielding the essential methylprednisolone‐precursor premedrol by optimizing the CYP21A2‐based whole‐cell system on a laboratory scale. We successfully improved the whole‐cell process in terms of premedrol production by (a) improving the electron supply to CYP21A2; here we use the N‐terminally truncated version of the bovine NADPH‐dependent cytochrome P450 reductase (bCPR−27) and coexpression of microsomal cytochrome b5; (b) enhancing substrate access to the heme by modification of the CYP21A2 substrate access channel; and (c) circumventing substrate inhibition which is presumed to be the main limiting factor of the presented system by developing an improved fed‐batch protocol. By overcoming the presented limitations in whole‐cell biotransformation, we were able to achieve a more than 100% improvement over the next best system under equal conditions resulting in 691 mg·L−1·d−1 premedrol.

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The effect of various anti‐inflammatory drugs on the accumulation of leucocytes in the peritoneal cavity of mice

Northover

1964

J. Pathol.

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Metabolic and Anti-inflammatory Properties of 6-Methyl Prednisolone Alone and in Combination with Anabolic Hormones

Cited by 13 publications

References 0 publications

Metabolic pathways and control mechanisms involved in the biosynthesis and turnover of collagen in normal and pathological connective tissues

Metabolic pathways and control mechanisms involved in the biosynthesis and turnover of collagen in normal and pathological connective tissues

Identification and circumvention of bottlenecks in CYP21A2‐mediated premedrol production using recombinant Escherichia coli

The effect of various anti‐inflammatory drugs on the accumulation of leucocytes in the peritoneal cavity of mice

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