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Biomedical subjects

J Marie

Publications and source records attributed to J Marie.

At least 55 records · Page 3Linked to original sources
PubMed1986

Sequences complementary to the brain-specific "identifier" sequences exist in L-type pyruvate kinase mRNA (a liver-specific messenger) and in transcripts especially abundant in muscle.

A sequence complementary to the brain-specific identifier sequence has been found in the 3' untranslated extension of the heavy 3.2-kilobase (kb) long liver L-type pyruvate kinase mRNA while it is absent in the other two 2- and 2.2-kb long pyruvate kinase mRNA species. A 53-base fragment corresponding to this identifier sequence was subcloned in both orientations in the single-stranded bacteriophage M13, both strands being used as probes to detect homologous sequence in different tissues. Both strands are transcribed in various tissues and are detected in heterogeneous high molecular weight RNA species which are especially abundant in the adult muscle. In addition, the probe identical to the identifier sequence recognized a discrete 0.6-kb RNA species in the muscle and the probe complementary to the identifier-sequence recognized the expected two small brain-specific identifier BC-1 and BC-2 RNAs described by Sutcliffe et al. (Sutcliffe, J. G., Milner, R. J., Bloom, F. E., and Lerner, R. A. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 4942-4946; Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., and Lerner, R. A. (1984) Nature 308, 237-241; Milner, R. J., Bloom, F. E., Lai, C., Lerner, R. A., and Sutcliffe, J. G. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 713-717; Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., and Reynolds, W. (1984) Science 225, 1308-1314).

Animals↗
PubMed1986

Complete nucleotide and deduced amino acid sequences of rat L-type pyruvate kinase.

Four overlapping cDNA clones for L-type pyruvate kinase (PK-L) were isolated from carbohydrate-induced rat liver cDNA libraries. They contained all the coding sequence of the enzyme from the 7th codon and the entire 3'-untranslated extension up to the poly(A) tail. The sequence of the first 7 codons and that of the 5'-untranslated region were determined by primer extension. The analyzed PK-L mRNA has 19 5'-untranslated bases, 1629 coding bases and 1281 3'-untranslated bases without the poly(A) tail; it corresponds to the heavier, 3.2 kb species of the L-type mRNAs. The codons for the phosphorylatable site are located at the 5'-end of the messenger. The unusually long 3'-untranslated extension contains a repetitive element complementary to the 'brain-specific' identifier sequence described by Sutcliffe et al. [(1982) Proc. Natl. Acad. Sci. USA 79, 4942-4946].

Amino Acid Sequence↗
PubMed1986

Vasopressin antagonists allow demonstration of a novel type of vasopressin receptor in the rat adenohypophysis.

The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from the determination of the concentration-dependent inhibition of [3H]vasopressin binding. In parallel experiments the corticotropin (or anti-corticotropin)-releasing activities of the tested peptides were determined on freshly dispersed rat adenohypophyseal cells. All peptides tested which were found to be antagonists of the vasopressor and antidiuretic responses to vasopressin in vivo behaved as antagonists of vasopressin-induced corticotropin release. There was a close correlation between the relative affinities of the analogues tested for binding to adenohypophyseal membranes and their relative potencies in inhibiting vasopressin-induced corticotropin release, indicating that the detected vasopressin-binding sites are the receptors involved in the vasopressin effect on corticotropin secretion. No correlation could be demonstrated between anti-corticotropin-releasing activities and either anti-antidiuretic or antivasopressor potencies of the antagonists tested. A direct comparison of the ligand specificities of adenohypophyseal receptors on the one hand, and V1 (hepatic) and V2 (renal) receptors on the other hand, showed that most of the antagonists discriminated very efficiently between adenohypophyseal and either hepatic or renal receptors. The selectivity index reaches values as high as 260,000 for desGly(NH2)9 [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-D-O-ethyl-tyrosine, 4-valine] arginine vasopressin. It is concluded that adenohypophyseal receptors represent a novel type of vasopressin receptors. Based on the observation that adenohypophyseal receptors, like hepatic or vascular V1 receptors, do not appear to be coupled to adenylate cyclase, we propose that adenohypophyseal receptors could be designated as V1b receptors as opposed to the V1a receptors previously characterized on liver and blood vessels.

Adrenocorticotropic Hormone↗
PubMed1986

High yield photoaffinity labeling of angiotensin II receptors.

The angiotensin II analogues, [Sar1, (4'-N3)Phe8]All and [Sar1, (4'-N3)D-Phe8]All were synthetized and prepared in their iodinated and radioiodinated forms. On rat liver membranes 125I-SarN3PheAll and 125I-SarN3DPheAll labeled a single population of sites (maximal binding capacity, 1.13 +/- 0.16 pmol/mg of protein) with high affinity (dissociation constants of 0.18 +/- 0.05 and 0.37 +/- 0.16 nM, respectively) and high specificity (nonspecific binding less than 10% of total binding for an 0.8 fractional receptor occupancy). 125I-SarN3PheAll and 125I-SarN3DPheAll allowed photoaffinity labeling of liver angiotensin receptors with high efficiency. The yield of photoaffinity labeling was independent of fractional receptor occupancy. 125I-SarN3PheAll and 125I-SarN3DPHeAll allow recovery in a soluble and covalently labeled form of about 40% of the total number of angiotensin receptors from rat liver membranes. For this reason they can be considered as potentially very useful tools for the purification of angiotensin receptors. The material covalently labeled with the antagonist 125I-SarN3DPHeAll was eluted from an Ultrogel ACA34 column as a homogeneous peak (Stoke's radius: 5.5 +/- 0.2 nm). The material covalently labeled with the agonist 125I-SarN3PHeAll was more heterogeneous. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of 125I-SarN3PheAll- and 125I-SarN3DPHeAll-labeled material revealed a single component of 63,000 molecular weight.

Adenylyl Cyclases↗
PubMed1985

Characterization and metabolic regulation of a liver-specific 5.4-kilobase mRNA whose synthesis is transcriptionally induced by carbohydrates and repressed by glucagon and cyclic AMP.

Four clones derived from a carbohydrate-induced rat liver cDNA library were found to hybridize with a 5.4-kilobase mRNA species encoding a 36 kDa protein. This mRNA was abundant in the liver, barely detectable in adipocytes and kidney, and absent from the other tissues tested. In the liver, the mRNA was fully induced by a carbohydrate-rich diet, but was undetectable during both starvation and feeding with a protein-rich or lipid-rich diet. Adrenalectomized, thyroidectomized and diabetic animals did not express the mRNA in their liver when re-fed with the carbohydrate-rich diet. When these animals were given the missing hormone, the amount of hybridizable RNA returned to normal values, but administration of the hormone alone failed to induce mRNA synthesis in starved animals. Both glucagon and its second messenger, cyclic AMP, abolished the induction of the mRNA in re-fed animals. Exogenous insulin, whatever the dose, did not reverse the inhibitory action of glucagon. In an isolated nuclei transcription system, no detectable RNA transcripts were found in starved animals, whereas feeding the animals with the carbohydrate-rich diet led to a maximum rate of gene transcription. Although unidentified, this mRNA proves to be a remarkable marker of dietary and hormonal control of gene expression in vivo. It will provide a useful model for further analysis of the role of cyclic AMP in regulating the transcription of eukaryotic genes.

Animals↗
PubMed1985

Pharmacological characterization of the angiotensin receptor negatively coupled with adenylate cyclase in rat anterior pituitary gland.

Angiotensin II (AII) inhibited anterior pituitary adenylate cyclase. Whereas GTP was necessary to fully express the AII inhibitory effect, Na+ was not required. The magnitude of inhibition (42 +/- 6%) permitted a pharmacological characterization of the AII receptor involved in adenylate cyclase inhibition. Angiotensin I (AI) was less potent than AII, and deletion of aminoacids in the N-terminal position resulted in a progressive reduction of the Ki (peptide concentration producing half-maximal inhibition). The Ki values were 3 +/- 0.9, 10, and 700 nM for AII, angiotensin III (AIII), and des-Asp, des-Arg-AII, respectively. Sarcosine in position 1 [( Sar, Phe]AII) increased the potency of inhibition (Ki = 0.12 +/- 0.12 nM). Different antagonists of the AII receptors appeared to be partial agonists. There was a very close correlation (r = 0.98) between the respective potencies of a series of AII analogs to inhibit adenylate cyclase and the potencies of these analogs to elicit PRL or ACTH release or to bind to AII-binding sites. Dopamine and AII inhibition of anterior pituitary adenylate cyclase were not additive. This suggests that both receptors are on the same cell and likely on lactotrophs. This hypothesis agrees with the observation that vasoactive intestinal peptide stimulation of adenylate cyclase was inhibited by AII, whereas corticotropin-releasing factor stimulation was unaffected. Although dopamine and AII inhibited the same adenylate cyclase, they had opposing effects on PRL release (inhibition and stimulation, respectively). The possible significance of this observation is related to a model implying that PRL release can be elicited through either a Ca+2 or a cAMP pathway.

Adenylyl Cyclase Inhibitors↗
PubMed1984

Cyclic AMP as a transcriptional inhibitor of upper eukaryotic gene transcription.

Recently, glucagon and its second messenger, cyclic AMP, have been shown to stimulate the transcription rate of several upper eukaryotic genes (1-5). We show here that glucagon can also block gene transcription. Both glucagon and cyclic AMP were found to inhibit the transcription of the genes encoding three liver glycolytic enzymes, including L-type pyruvate kinase and aldolase B. Thus, cyclic AMP proves to be not only an activator but also an inhibitor of gene transcription in eukaryotes.

Animals↗
PubMed1984

In vivo hormonal control of L-type pyruvate kinase gene expression. Effects of glucagon, cyclic AMP, insulin, cortisone, and thyroid hormones on the dietary induction of mRNAs in the liver.

Using a cDNA probe complementary to rat L-type pyruvate kinase mRNAs, we studied the respective roles of glucocorticoids, thyroid hormones, glucagon, and insulin in the induction of specific mRNAs in the liver of animals refed either a maltose-rich or a fructose-rich diet. Neither adrenalectomized nor thyroidectomized nor diabetic animals could express L-type pyruvate kinase mRNAs in their liver when refed the carbohydrate-rich diets. When the animals were given the missing hormone, the level of hybridizable mRNAs returned to normal values but administration of the hormone alone failed to induce mRNA synthesis in fasted animals. Both glucagon and cyclic AMP abolished the induction of L-type pyruvate kinase mRNAs in refed animals. Exogenous insulin, whatever the dose, could not reverse the inhibitory action of glucagon. Insulin has usually been regarded as the main regulator of L-type pyruvate kinase gene expression. It appears now that glucagon, beside regulating the enzyme activity by phosphorylation mechanisms, may also modulate L-type pyruvate kinase synthesis at a pre-translational level. Consequently, our results show that three conditions are required for the synthesis of liver L-type pyruvate kinase mRNAs: (i) the presence of dietary carbohydrates, (ii) the cessation of glucagon release, and (iii) the presence of permissive hormones, including insulin.

Adrenalectomy↗
PubMed1984

Adrenocorticotropin regulates angiotensin II receptors in bovine adrenal cells in vitro.

The role of ACTH-(1-24) on angiotensin II receptors has been studied in bovine adrenal glomerulosa cells in primary culture. Angiotensin II receptors were measured in cells pretreated or not by ACTH-(1-24) on day 4 of culture. ACTH-(1-24) decreased angiotensin II binding sites in a time and a dose-dependent manner. After 24 hours of treatment the minimal effective dose of ACTH-(1-24) was 10(-11)M and the maximal effect was obtained with 10(-8)M. Moreover, ACTH-(1-24) 10(-8)M decreased significantly angiotensin II receptors after 6 hours of treatment. Scatchard plot analysis showed that ACTH-(1-24) treatment did not modify the affinity of angiotensin II receptors (Ka = 0.42 and 0.44 X 10(9)M-1 in control and treated cells respectively) but reduced by about half the number of angiotensin II sites per cell. Like ACTH-(1-24), 8-Bromo-cAMP, forskolin and cholera toxin decreased angiotensin II receptors. Factors such as prolactin, somatostatin, ACTH-(11-24) and dopamine which are bound to adrenal membranes without increasing cAMP production had no effect. In conclusion, these studies in vitro demonstrate for the first time that ACTH decreases angiotensin II receptors by a direct mechanism acting on glomerulosa cells, and they also suggest that this effect could be mediated by cAMP.

Adrenal Glands↗
PubMed1984

Dietary control of aldolase B and L-type pyruvate kinase mRNAs in rat. Study of translational activity and hybridization with cloned cDNA probes.

Liver L-type pyruvate kinase and aldolase B mRNAs are the two species whose translational activity increases the most after feeding starved rats a high carbohydrate diet (Simon, M. P., Besmond, C., Cottreau, D., Weber, A., Chaumet-Riffaud, P., Dreyfus, J. C., Sala Trépat, J., Marie, J., and Kahn, A. (1984) J. Biol. Chem., in press). We therefore compared the pattern of this induction in three tissues synthesizing these enzymes, e.g. the liver, small intestine, and kidney. Influence of high lipid and protein diets on liver L-type pyruvate kinase and aldolase B mRNAs was also investigated. In the starved rat livers, L-type pyruvate kinase mRNA was practically undetectable. Carbohydrate diet induced an increase of both mRNA concentrations, with a maximum at the 12-18th h; at this time, mRNA concentration was increased about 4-8 times for aldolase B and 40-100 times for L-type pyruvate kinase, translational activities representing about 1% of the total mRNA activity for both enzymes. After the 24th h of carbohydrate diet, mRNA concentrations decreased slightly, then remained in plateau. In animals refed the high carbohydrate diet, starvation as well as high lipid and protein diets provoked a rapid decrease of both mRNA concentrations and translational activities. In the kidney, aldolase B mRNA synthesis was high in starved rats and was only slightly stimulated by carbohydrates (1.5-2.5 times). L-type pyruvate kinase mRNA concentration was increased 6-15-fold after feeding a high carbohydrate diet. In the small intestine, in contrast, the extent of aldolase B mRNA induction by a carbohydrate diet was similar to that in the liver, while L-type pyruvate kinase mRNA concentration was practically similar in starved and refed rats (about 1:10 of the concentration observed in refed rat liver). These results seem to indicate that the mechanisms responsible for carbohydrate induction of L-type pyruvate kinase and aldolase B are different. In addition, dietary control of each enzyme is also different in the various tissues which synthesize them.

Animals↗
PubMed1984

Properties of rat anterior pituitary vasopressin receptors: relation to adenylate cyclase and the effect of corticotropin-releasing factor.

Crude plasma membrane fractions were prepared from female Wistar rat anterior pituitaries. These fractions contained a single population of specific 3H-labeled [8-lysine]vasopressin [( 3H]vasopressin) binding sites with a dissociation of constant (Kd) of 8 +/- 2 X 10(-9) M and maximal binding capacity of 244 +/- 45 fmol/mg of protein. The Kd values for a series of vasopressin structural analogues with selective vasopressor or antidiuretic activities were determined together with the corresponding corticotropin-releasing activities (isolated perfused pituitary cells were used). A good correspondence was found between the two sets of values, suggesting that the detected vasopressin binding sites are the receptors involved in vasopressin-induced corticotropin release. The order of potency of these analogues for the binding to hypophysial receptors was similar to that found for the binding to the receptors involved in the vasopressor response. Corticotropin-releasing factor and angiotensin did not affect vasopressin binding to pituitary membranes. Median eminence extracts inhibited [3H]vasopressin binding with an efficiency very close to that expected from their vasopressin content. Corticotropin-releasing factor activated, and angiotensin inhibited, the adenylate cyclase activity of pituitary membranes. Under the same experimental conditions, vasopressin did not influence adenylate cyclase activity nor did it affect the corticotropin-releasing factor-induced activation. These data support the view that vasopressin is one component of the multifactorial regulation of corticotropin release and that it acts through a cAMP-independent pathway. The potentiation by vasopressin of corticotropin-releasing factor-induced cAMP accumulation in intact cells very likely proceeds through indirect mechanisms, which are not expressed in broken cell preparations.

Adenylyl Cyclases↗
PubMed1984

Testosterone, dihydrotestosterone, androstenedione and dehydroepiandrosterone concentrations in placentae, ovaries and plasma of the rat in late pregnancy.

Testosterone (T), dihydrotestosterone (DHT), androstenedione (delta 4) and dehydroepiandrosterone (DHA) were measured by radioimmunoassay in peripheral plasma, uterine vein plasma, ovary and placentae within the last 3-4 days of pregnancy in Sprague-Dawley rats. In the uterine vein, T and delta 4 levels were significantly higher than those reported in the peripheral plasma at any particular day of late pregnancy. In peripheral plasma as in uterine vein plasma delta 4 and T gradually decreased from day 20 to term (-63% for delta 4 and approximately -45% for T) whereas DHT concentrations were unchanged. This decline is concomitant with a similar pattern of change in the placentae; indeed placental concentrations of delta 4 and T decreased significantly from day 19 to 22 (-63 and -79%, respectively) and were positively correlated with the levels of both androgens in uterine venous and peripheral plasma. Thus it was concluded that in the late phase of pregnancy in the rat circulating delta 4 and T originate from placentae. In contrast, ovarian androgen concentrations showed a sharp increase from day 21 to term: 58% for DHA, 49% for delta 4, 87% for T and 24% for DHT. It is suggested that these increasing concentrations of ovarian androgens could be related to the next ovulatory cycle.

Androstenedione↗
PubMed1984

Angiotensin-induced changes in the apparent size of rat liver angiotensin receptors.

Angiotensin receptors from rat liver were labeled using four different ligands: (Sar1-(3H)Tyr4)-Angiotensin ll ((3H)SarAll); (Sar1-(3H)Tyr4-lle8)-Angiotensin ll ((3H)SarlleAll); (Sar1-(125I) Tyr4-(4'-N3) Phe8)-Angiotensin ll (IN3All); (Sar1-(125I)Tyr4-(4'N3D-Phe)8)-Angiotensin ll (IN3DPheAll). (3H)SarAll and IN3All behaved like agonists and (3H)SarlleAll and IN3DPheAll like antagonists. All four ligands labeled the same population of sites. The azido derivatives allowed covalent labeling of receptors with a high yield (about 40%). Membranes were solubilized by Triton X-100 under experimental conditions which ensured complete solubilization of the liganded receptors in a stable form (less than 40% dissociation after 20 h). The apparent size of liganded angiotensin receptors was determined by gel filtration on Ultrogel ACA-34 columns and by SDS gel electrophoresis (in the case of covalent labeling). The apparent Stokes radius of solubilized angiotensin receptors was different wether the receptor was labeled with an agonist (Stokes radius = 6.2 +/- 0.1 nm (6) after labeling with (3H)SarAll) or with an antagonist (Stokes radii of 5.5 +/- 0.1 (7), and 5.6 +/- 0.1 nm (4) after labeling with (3H)SarlleAll and IN3DPheAll respectively). After covalent labeling with IN3All angiotensin receptors were eluted as a mixture of light and heavy forms. SDS gel electrophoresis revealed only one molecular entity of Mr 64,000. It is concluded that binding of an agonist to liver angiotensin receptors triggers or stabilizes an interaction with another membrane component involved in the coupling of the receptor to its primary effector.

Angiotensin II↗
PubMed1983

Molecular cloning of cDNA for rat L-type pyruvate kinase and aldolase B.

Two double-stranded cDNA recombinant pBR322 plasmid libraries were constructed starting from high carbohydrate diet rat liver poly(A)+ mRNA, either fractionated by denaturing sucrose gradient centrifugation for the cloning of L-type pyruvate kinase cDNA, or nonfractionated for aldolase B. Both libraries were screened with single-stranded cDNA probes reverse transcribed from fasted or high carbohydrate diet rat liver mRNAs. mRNAs from fasted animals were also fractionated by sucrose gradient centrifugation and mRNAs from the fed animals were, in addition, further purified by high performance liquid gel filtration chromatography. Those clones hybridizing with the "positive" probe (from animals fed the high carbohydrate diet) and not with the "negative" one (from fasted animals) were preselected and their plasmid DNA was purified and analyzed by positive hybridization-selection. Thirty of 4500 bacteria colonies transformed by recombinant plasmids were preselected by differential screening for pyruvate kinase, and 8 of 864 colonies for aldolase B. Twenty-two recombinant plasmids for pyruvate kinase and two for aldolase B were shown to contain specific cDNA inserts by positive hybridization-selection. Plasmids DNAs of some pyruvate kinase and aldolase B clones (whose inserts ranged from 700 to 1050 bases in length) were labeled by nick translation and used as probes for Northern blot hybridization. The pyruvate kinase cDNA probes recognized mainly a 3400-base RNA species which was detected in high carbohydrate diet rat liver, but not in fasted rat liver and in tissues which do not synthesize L-type pyruvate kinase. In addition, some pyruvate kinase probes hybridized with minor RNA species of about 2000 bases in length, only observed after carbohydrate diet. For aldolase B, the recombinant plasmid DNA hybridized with a single RNA species of 1750 bases. This RNA, detected in kidney, small intestine and liver, was induced by a high carbohydrate diet and increased with liver development. The rat probe cross-hybridized with human aldolase B messenger RNA.

Animals↗
PubMed1983

Angiotensin II inhibits adenylate cyclase from adrenal cortex glomerulosa zone.

Angiotensin binding and the effects of angiotensin on adenylate cyclase activity were determined on purified membranes from the glomerulosa zone of bovine adrenal cortex. Angiotensin II inhibited adenylate cyclase activity in a dose-dependent manner with an A50-value of 2 nM. The angiotensin effect required the presence of GTP. Angiotensin also inhibited ACTH-stimulated activity. Angiotensin binding was sensitive to the same effectors which influenced angiotensin-induced adenylate cyclase inhibition. In the presence of NaCl 100 mM and magnesium, angiotensin interacted with a single population of binding sites (Kd = 4 nM and maximal binding capacity of 440 fmol/mg protein). These results and published data suggest that the ability to inhibit adenylate cyclase might be a general property of angiotensin receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1983

A critical period in the onset of parturition in rats and uterine sensitivity to estradiol and progesterone.

The purpose of this paper was to impair normal parturition in rats in order to measure tissue levels of progestins and estrogens and compare these results with those of normal parturition in rats. Abnormal parturition was obtained by injection of isotonic saline into the uterine lumen of pregnant rats at the end of pregnancy or by handling the uterus. After each of these treatments on day 21 of pregnancy, parturition was impaired in 70 to 98% of the rats. When the treatments were carried out earlier or later in pregnancy, there was little or no impairment. Our results indicate transient discrepancies in plasma and tissue levels of steroids 6 h after treatment on day 21: 20 alpha-HP concentrations increased in treated rats compared to controls (uteri: 470%; p less than 0.01; ovaries: 89%; p less than 0.001); concomitantly, there was a sharp rise in P concentrations in uteri (+ 74% : p less than 0.05) and ovaries (+ 52%; p less than 0.05). Inversely, uterine concentrations of E2 decreased 6 h after treatment compared to controls (- 30%; p less than 0.05), although there was a transient rise of E2 in the ovaries (+ 30%; p less than 0.05). Twenty-four hours later, E2 concentrations were always lower in the uteri (- 30%; p less than 0.01). No change in E2 levels was noted in the uteri or ovaries of either the control or treated rats. The physiological significance of these changes and their consequences on uterine reactivity at term have been discussed. The data demonstrate that day 21 was a critical period in the parturient activity of the rat uterus which appears to be primarily affected by uterine levels of E2 between days 21 and 22 of pregnancy.

20-alpha-Dihydroprogesterone↗
PubMed1983

Genetic and epigenetic control of the pyruvate kinase isozymes in mammals.

In man, patients with hereditary red cell pyruvate kinase (PK) deficiency have their enzyme concomitantly affected in both red cells and liver (PK-L), such that red cell L' and liver L PK subunits appear to be encoded by the same structural gene. Very recently, a mutant M1 PK has been described in muscle from a special mouse strain in which the M2 PK was concomitantly modified. Thus, it has been suggested that the M1 and M2 PK subunits are also encoded by the same structural gene, a gene distinct from that encoding L' and L. In this paper, we show that synthesis of each of the four PK subunits is specified by a different specific mRNA. Two structural genes, but at least four different mRNAs seem therefore to control synthesis of the PK isozymes. Genetic and epigenetic mechanisms responsible for generation of this diversity at the RNA level are discussed. In addition to these mechanisms of PK diversity, some PK subunits can be modified by post-translational events. In red cells, for instance, cell aging is associated with a progressive, partial proteolysis of the C-terminal extremities of L' subunits, ultimately resulting in cleavage of the phosphorylatable site.

Animals↗