Polyamines in rapid growth and cancer

Normal young adult male and female subjects were maintained on fixed dietary regimens which were either essentially normal or were semisynthetic and curtailed in methionine and choline intakes and virtually free of cystine. The subjects maintained stable weights and remained in positive nitrogen balance or within the zone of sulfur equilibrium. Choline intakes were calculated, and urinary excretions of creatinine, creatine, and sacrosine were measured. Creatinine excretions of male subjects on essentially normal diets outweighed the total intakes of labile methyl groups. Taking into account the excretions of additional methylated compounds, as judged from published values, it appears that methyl neogenesis must normally play a role in both males and females. When labile methyl intake is curtailed, de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties. On the normal diets used in these experiments, the average homocysteinyl moiety in males cycled between methionine and homocysteine at least 1.9 times before being converted to cystathionine. For females, the average number of cycles was at least 1.5. When labile methyl intake was curtailed, the average number of cycles rose to 3.9 for males and 3.0 for females under the conditions employed.

Labile methyl balances for normal humans on various dietary regimens.

Ornithine decarboxylase: a key regulatory enzyme in normal and neoplastic growth.

This chapter deals with the structure and replication of herpesviruses in susceptible cells. Having stated its scope, we shall take license to say what what we think of it.

The Replication of Herpesviruses

Summary Patients with histologically diagnosed tumors and leukemias have an average 24-hr excretion value for polyamines that is severalfold greater than that detectable in “normals”. In leukemias, the excretion level declines when the patients are in remission. After surgery for the removal of a portion of a solid tumor mass, polyamine levels in the urine decreased to near normal in all cases. It is possible, therefore, that polyamine excretion levels could serve as (a) a tool to monitor cancer and (b) a test that could lead to an early detection of cancer.

https://cancerres.aacrjournals.org/content/canres/31/11/1555.full.pdf

Urinary Polyamines in Cancer Patients

The Dynamics of Synthesis and Degradation of Polyamines in Normal and Regenerating Rat Liver and Brain

The effect of growth hormone on hepatic ornithine decarboxylase (L-ornithine carboxy- lyase, EC 4.1.1.17) (ORD) activity was studied in adult and weanling rats. Single injections of growth hormone produced up to 30-fold increases in ORD activity in both adults and weanlings. However, with lower doses of growth hormone, a greater increase in ORD activity occurred in weanlings than in adults. Both adult and weanling rats showed the same time course of ORD activity enhancement after growth hormone with peak enzymatic activity at 4 hr and a decline to basal levels by 8 hr after hormone administration. In weanling rats, cycloheximide completely prevented the elevation of ORD activity at 4 hr after growth hormone if administered any time up to 3 hr after the hormone. If given simultaneously with growth hormone, actinomycin D almost totally supressed the enhanced ORD activity 4 hr after growth hormone. However, the ability of actinomycin D to prevent increased ORD activity decreased as the time after growth horm...

Growth Hormone Induction of Ornithine Decarboxylase in Rat Liver

The polyamines include spermidine and spermine, whereas putrescine is a diamine. Spermine and spermidine derive their names from their discovery as constituents of human seminal plasma. They are secreted by the prostate, the mammalian tissue with the highest concentration of polyamines.5G Other mammalian tissues with high polyamine levels include the pancreas and bone marrow, both very active synthesizers of protein, as is the prostate gland.S6 Polyamines occur ubiquitously in animal and plant tissues, and in microorganisms. In E. coli, RNA and sperimidine concentrations increase in a parallel Moreover, exogenous spermidine can relax RNA synthesis in polyauxotropic strains of E . ~ o l i . ~ ~ Polyamines can stabilize ribosomal RNA as well as DNA and a variety of membranous structures.56 These properties, along with the high concentrations in tissues that actively synthesize protein and the correlation of polyamine and RNA levels, suggest a role for these compounds related to polynucleotides and protein synthesis. In animal tissues several lines of evidence have indicated a relationship of polyamines to rapid tissue growth. Thus, in regenerating rat liver spermidine accumulation parallels increases of RNA,'O* 17, 3L) and there is a marked enhancement of the incorporation of isotopic precursors into liver spermidine.l7. 39 In the developing chick embryo, spermidine and RNA concentrations increase at similar rates.* Hypophysectomy results in a decline in the content of spermidine in the rat liver that can be restored by treatment with growth hormone.24 The synthetic pathway for the formation of polyamines involves the convergence of two amino acids, ornithine and methionine (FIGURE 1). Ornithine is decarboxylated by an enzyme which has been described in E. coli5G and in rat prostate 30 and forms putrescine (diaminobutane) . L-methionine is converted to S-adenosylmethionine by an enzyme which appears to have similar properties in liver, yeast, and E. coli.51; S-adenosylmethionine is then decarboxylated and the propylamine moiety of the decarboxylated adenosylmethio-

Vicente J. Medina

Papers

The Dynamics of Synthesis and Degradation of Polyamines in Normal and Regenerating Rat Liver and Brain

Growth Hormone Induction of Ornithine Decarboxylase in Rat Liver

Polyamine synthesis and turnover in rapidly growing tissues

Presence and biosynthesis of putrescine and polyamines in amphibians.