Potentiating action of 4-vinylpyridoxal on inhibition of serine transhydroxymethylase by d-cycloserine and its dimer

Bukin, Yuriy V.; Draudin-Krylenko, V A; Korytnyk, W.

doi:10.1016/0006-2952(79)90181-3

Cited by 6 publications

(2 citation statements)

References 9 publications

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“…Moreover, serine hydroxymethyltransferase has the advantage that its inhibition not only interferes with the synthesis of the pyrimidine, thymidylate, but also with the formation of glycine as a purine base precursor (Figure 1). (Bukin et al, 1979). D-Fluoroalanine, an active site-directed suicide inhibitor of the enzyme, has also been shown to be inhibitory in vitro (Wang et al, 1981).…”

Section: General Conclusion and Implications For Anti-cancer Therapymentioning

confidence: 99%

Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma

Snell

Natsumeda²,

Eble³

et al. 1988

Br J Cancer

114

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Summary The activities of 3-phosphoglycerate dehydrogenase, an enzyme of serine biosynthesis, and serine hydroxymethyltransferase, serine dehydratase and serine aminotransferase, which are competing enzymes of serine utilization, were assayed in human colon carcinomas from patients and in transplantable rat sarcomas. Serine dehydratase and serine aminotransferase activities were absent, whereas 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase activities were markedly increased in both tumour types. Serine hydroxymethyltransferase catalyses the formation of glycine and methylene tetrahydrofolate which are important precursors for nucleotide biosynthesis. The observed enzymic imbalance in these tumours ensures that an increased capacity for the synthesis of serine is coupled to its utilisation for nucleotide biosynthesis as a part of the biochemical commitment to cellular replication in cancer cells. That this pattern is found in sarcomas and carcinomas, and in tumours of human and rodent origin, signifies its universal importance for the biochemistry of the cancer cell and singles it out as a potential target site for anti-cancer chemotherapy.

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Section: General Conclusion and Implications For Anti-cancer Therapymentioning

confidence: 99%

Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma

Snell

Natsumeda²,

Eble³

et al. 1988

Br J Cancer

114

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“…Bukin & Sergeev (1968) reported that D-cycloserine selectively inhibited serine hydroxymethyltransferase (EC 2.1.2.1) in mouse liver extracts and in the liver of mice receiving a diet deficient in PLP. The pronounced antineoplastic activity of D-cycloserine and its dimer (Bukin et al, 1970;Sergeev et al, 1971;Draudin-Krylenko, 1976; Bukin & Draudin-Krylenko, 1980), especially in combination with 4-vinylpyridoxal (Bukin et al, 1979), suggested that serine hydroxymethyl transferase might play a critical role in maintaining neoplasia (Bukin & Draudin-Krylenko, 1980).…”

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confidence: 99%

Kinetic mechanism of the interaction of D-cycloserine with serine hydroxymethyltransferase

Manohar¹,

Rao²,

Rao³

1984

Biochemistry

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The kinetic mechanism for the interaction of D-cycloserine with serine hydroxymethyltransferase (EC 2.1.2.1) from sheep liver was established by measuring changes in the activity, absorbance, and circular dichoism (CD) of the enzyme. The irreversible inhibition of the enzyme was characterized by three detectable steps: an initial rapid step followed by two successive steps with rate constants of 5.4 X 10(-3) s-1 and 1.4 X 10(-4) s-1. The first step was distinguished by a rapid disappearance of the enzyme absorbance peak at 425 nm, a decrease in the enzyme activity to 25% of the uninhibited velocity, and a lowering of the CD intensity at 432 nm to about 65% of the original value. The second step of the interaction was accompanied by a complete loss of enzyme activity and a marginal increase in the CD intensity at 432 nm. The final step resulted in the complete loss of the enzyme absorbance at 425 nm and of the CD band at 432 nm. The products of the reaction were identified as (a) apoenzyme by absorbance measurements, CD spectra, and reconstitution with pyridoxal 5'-phosphate and (b) a pyridoxal 5'-phosphate-D-cycloserine Schiff's base complex identified by its fluorescence and absorbance spectra. The Schiff base complex was expelled from the enzyme active site in the final step of the reaction. The proposed mechanism, which is different from those operative in other pyridoxal phosphate dependent enzymes, probably accounts for the selective inhibition of serine hydroxymethyltransferase by the drug in vivo.

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The thymidylate synthesis cycle and anticancer drugs

Douglas

1987

Medicinal Research Reviews

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Potentiating action of 4-vinylpyridoxal on inhibition of serine transhydroxymethylase by d-cycloserine and its dimer

Cited by 6 publications

References 9 publications

Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma

Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma

Kinetic mechanism of the interaction of D-cycloserine with serine hydroxymethyltransferase

The thymidylate synthesis cycle and anticancer drugs

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