Biochemistry - Publicatons

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    Modifying effects of divalent ions on the sulfhydryl content of normal and tumorous beet root tissue under thermal and γ-irradiation stress
    ( 1981-02-01) Ramaiah, K. V.Atchuta ; Mookerjee, Anjali
    Temperature and γ-irradiation stresses result in the loss of DTNB (5-5′ Dithionitrobenzoic acid) - reactive sulfhydryl groups in the TCA (trichloroacetic acid)-insoluble protein of normal and tumorous beet root tissue. Metal ions like Ca2+, Zn2+, and Pb2+ have been found to partially prevent the change of-SH quantity under stress conditions. An attempt has been made to correlate the observed loss of DTNB - reactive sulfhydryl content with the loss of membrane permeability under thermal and irradiation conditions. © 1981 Birkhäuser Verlag.
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    A comparative study of membrane related phenomena in normal and crown gall tissues of red beet (Beta vulgaris L.)
    ( 1982-11-01) Atchuta Ramaiah, K. V. ; Mookerjee, A.
    Divalent metal ions have been found to protect membranes of red beet crown gall tissue more than their adjacent normal regions from thermal or gamma radiation stress, suggesting the possibility of an alteration on the surface charge accompanying tumor formation in plants. Further, tumor tissue has been observed to possess enhanced membrane ATPase activity, a higher tissue sulfhydryl content and increased protein levels, thus suggesting a model of 'source' (normal tissue) and 'sink' (tumor tissue) relationship. © 1982 Birkhäuser Verlag.
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    Wounding of aged pea epicotyls enhances the reinitiating ability of isolated ribosomes
    ( 1985-10-01) Ramaiah, K. V.A. ; Davies, Eric
    Total ribosomes (monosomes plus polysomes) isolated from wounded pea epicotyls are more efficient at supporting protein synthesis in a wheat germ S30 system (containing wheat ribosomes) than are total ribosomes from aged (control) pea tissue. This increased efficiency is seen when enriched large polysomes, almost devoid of monosomes, are used to program a wheat germ S300 system, from which the wheat germ ribosomes have been removed. Reactions primed by enriched polysomes from wounded tissue, but not aged tissue, continue for at least 30 min, suggesting that reinitiation is occurring during the reaction, albeit in the initial absence of monosomes from wheat or pea. Wheat germ ribosomes, but not monosomes from either aged or wounded pea tissue, are able to translate pea poly(A) RNA and globin mRNA. Aurintricarboxylic acid reduces protein synthesis in a rather indiscriminate manner, whereas, pactamycin seems to have an inhibitory effect specific for initiation, and it is much more effective on wounded than on control tissue polysomes. We interpret these results to imply that polysomal ribosomes from wounded tissue are more efficient at initiation than are polysomal ribosomes from control tissue or than non-polysomal ribosomes (monosomes) from either tissue. © 1985 The Japanese Society of Plant Physiologists.
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    Wounding inhibits protein synthesis yet stimulates polysome formation in aged, excised pea epicotyls
    ( 1986-01-01) Davies, Eric ; Ramaiah, K. V.A. ; Abe, S.
    Wounding of aged, previously-excised pea epicotyl segments by removal of the basal 1-2 mm resulted in a rapid (beginning within 15 min) recruitment of monosomes on to polysomes and an even more rapid (maximal between 6-12 min) inhibition of protein synthesis in the remaining tissue. This inhibition of protein synthesis in vivo did not appear to be an artefact caused by the removal of highly active tissue (e.g., callus, contaminating bacteria), since wounds inflicted at a site distant from the region analyzed still elicited the response, and protein synthesis in the 1-2 mm slices (normally discarded) was inhibited even more strongly than it was in the remaining tissue. The proportion of radioactive methionine in nascent chains (bound to polysomes) increased, while the production of completed polypeptides decreased, after wounding. Cycloheximide, a known inhibitor of the ribosome translocation/release process mimicked some of the effects of wounding. We interpret the results to indicate that the initial effect of wounding is to inhibit translation by inhibiting the ribosome translocation/release process, whereas the subsequent recovery in protein synthesis is brought about partly by a recovery in ribosome translocation/release and partly by enhanced initiation. © 1986 The Japanese Society of Plant Physiologists.
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    The nature of lectins from Dolichos lablab
    ( 1986-03-01) Siva Kumar, N. ; Rajagopal Rao, D.
    The lectins from the seeds of Dolichos lablab var. lignosus (field bean) and Dolichos lablab var. typicus (lablab bean) have been isolated in a homogeneous form by affinity chromatography on D-mannose linked Sepharose. Both the lectins are glycoproteins and have a molecular weight of 60,000 and S 20,w value of 5.2 and seem to be made up of 4 similar subunits (apparent molecular weight 15,000). The carbohydrate content ofthe lectins is mostly fucose (2-5 mol per mol of protein), mannose (5-8 mol per mol of protein) and N-acetyl glucosamine (1-2 mol per mol of protein). The amino acid composition of both the lectins was similar and methionine and half cystine could not be detected, Both the lectins have similar tryptic peptide map. Alanine and serine were the only N and C-terminal amino acids for both lectins. The lectins were found to contain low amounts of bound metals such as manganese, magnesium and calcium. The near ultra-violet circular dichroism spectra of the lectins are similar to that of Sainfoin. Circular dichroism data indicate that tyrosine and tryptophan residues are involved in sugar binding. The lectins are nonspecific for human blood groups and they agglutinate a variety of other erythrocytes. Among a number of sugars, D-glucose and D-mannose inhibited the haemag-glutinating activity ofthe lectins. The lectins were antigenically similar © 1986 Indian Academy of Sciences.
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    Mechanism of protein synthesis inhibition by vaccinia viral core and reversal of this inhibition by reticulocyte peptide chain initiation factors
    ( 1987-03-01) Chakrabarti, Debopam ; Ramaiah, Kolluru V.A. ; Roy, Ananda L. ; Bagchi, Milan ; Gupta, Naba K.
    Vaccinia viral core inhibits protein synthesis in heme-supplemented reticulocyte lysate. A reticulocyte cell suPernatant factor, which reversed Protein synthesis inhibition in heme-deficient reticulocyte lysate also reversed vaccinia viral core induced Protein synthesis inhibition in heme-suPPlemented reticulocyte lysate. Significant inhibition reversal activity was also observed with a partially purified eukaryotic initiation factor-2 PreParation and this activity was lost uPon further Purification of eukaryotic initiation factor-2.The ribosomal salt-wash factor Co-eukaryotic initiation factor-2 which like reticulocyte suPernatant factor contains guanine nucleotide exchange factor activity, was comPletely inactive. Vaccinia viral core induced detectable level of eukaryotic initiation factor-2 α-subunit phosphorylation when incubated in the heme-supplemented reticulocyte lysate. This lysate preparation contains guanine nucleotide exchange factor activity. However, when the same reticulocyte lysate was previously incubated with the vaccinia viral core, the guanine nucleotide exchange factor activity during subsequent incubation was almost comPletely inhibited. © 1987 Indian Academy of Sciences.
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    Antibodies against the cytoplasmic tail can differentiate between the quaternary forms of the M < inf > r < /inf > 46000 mannose 6-phosphate receptor
    ( 1991-03-11) Nadimpalli, Siva Kumar ; Schmidt, Bernhard ; von Figura, Kurt ; Hille, Annette
    An antiserum against a peptide of the cytoplasmic tail of the Mr 46000 mannose 6-phosphate receptor is described which recognizes preferentially the tetrameric versus the dimeric form of this receptor. This indicates that the conformation of the cytoplasmic tail, which harbours signals necessary for the trafficking of the receptor, depends on the quaternary structure of the receptor. © 1991.
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    Recycling and phosphorylation of eukaryotic initiation factor 2 on 60S subunits of 80S initiation complexes and polysomes
    ( 1992-01-01) Ramaiah, Kolluru V.A. ; Dhindsa, Rajinder S. ; Chen, Jane Jane ; London, Irving M. ; Levin, Daniel
    Phosphorylation of the α-subunit (38 kDa) of eukaryotic initiation factor 2 (eIF-2α) regulates initiation of protein synthesis in eukaryotic cells. This phosphorylation is enhanced in cycloheximide-treated heme-deficient reticulocyte lysates in which polysomes are maintained. In early heme deficiency prior to polysome disaggregation, eIF-2(αP) accumulates primarily on the 60S subunits of polysomes. Further, isolated polysomes contain eIF-2α that is efficiently phosphorylated in vitro by heme-regulated inhibitor (HRI). Immunoblot analysis of eIF-2 distribution in sucrose gradients of actively protein-synthesizing lysates indicates that eIF-2 is distributed at low levels throughout the polysome profiles. These findings suggest that polysome-bound eEF-2α is a target of HRI under physiological conditions. The presence of eIF-2 on the 60S subunits of polysomes is incompatible with the conventional model in which eIF-2 is recycled during the joining of the 48S preinitiation complex and the 60S subunit to form the 80S initiation complex. A modified model is presented with emphasis on the translocation of eIF-2 from the 40S ribosomal subunit of the 48S preinitiation complex (eIF-2·GTP·Met-tRNA·40S·mRNA) to the 60S subunit of the 80S initiation complex. (.
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    Tail-specific antibodies that block return of 46,000 M(r) mannose 6- phosphate receptor to the trans-Golgi network
    ( 1993-01-01) Schulze-Garg, C. ; Boker, C. ; Nadimpalli, S. K. ; Von Figura, K. ; Hille-Rehfeld, A.
    Recycling of 46,000 M(r) mannose 6-phosphate receptor (MPR 46) was investigated by microinjection of F(ab) fragments against small epitopes within the cytoplasmic domain of the receptor. F(ab) fragments against the peptide 43-47 (Ala-Tyr-Arg-Gly-Val) efficiently blocked return of MPR 46 to the TGN. Antibody-induced redistribution resulted in accumulation of MPR 46 within an endosomal compartment, from which it recycled to the plasma membrane. Rab5 and rab7, markers for early and late endosomes, respectively, were not detectable in the compartment of redistributed MPR 46, suggesting that it represents a specialized endosomal subcompartment. The bulk of redistributed MPR 46 did not colocalize with endocytosed fluid-phase marker, suggesting that it accumulates at a site where MPR 46 has been segregated from endocytosed material, which is destined for transport to lysosomes. Peptide 43-47 contains a tyrosine (residue 44) which has been shown earlier to be part of an internalization signal for MPR 46 (Johnson, K. F., W. Chan, and S. Kornfeld. 1990. Proc. Natl. Acad. Sci. USA. 87:10010-10014). The role of tyrosine residue 44 as part of a putative multifunctional sorting signal is discussed.
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    Expression of mutant eukaryotic initiation factor 2 α subunit (eIF-2α) reduces inhibition of guanine nucleotide exchange activity of eIF-2B mediated by eIF-2α phosphorylation
    ( 1994-01-01) Ramaiah, Kolluru V.A. ; Davies, Monique V. ; Chen, Jane Jane ; Kaufman, Randal J.
    The inhibition of protein synthesis that occurs upon phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2α) at serine 51 correlates with reduced guanine nucleotide exchange activity of eIF-2B in vivo and inhibition of eIF-2B activity in vitro, although it is not known if phosphorylation is the cause of the reduced eIF-2B activity in vivo. To characterize the importance of eIF-2α phosphorylation in the regulation of eIF-2B activity, we studied the overexpression of mutant eIF-2α subunits in which serine 48 or 51 was replaced by an alanine (48A or 51A mutant). Previous studies demonstrated that the 51A mutant was resistant to phosphorylation, whereas the 48A mutant was a substrate for phosphorylation. Additionally, expression of either mutant partially protected Chinese hamster ovary (CHO) cells from the inhibition of protein synthesis in response to heat shock treatment (P. Murtha-Riel, M. V. Davies, J. B. Scherer, S. Y. Choi, J. W. B. Hershey, and R. J. Kaufman, J. Biol. Chem. 268:12946-12951, 1993). In this study, we show that eIF-2B activity was inhibited in parental CHO cell extracts upon addition of purified reticulocyte heme-regulated inhibitor (HRI), and eIF-2α kinase that phosphorylates Ser-51. Preincubation with purified HRI also reduced the eIF-2B activity in extracts from cells overexpressing wild-type eIF-2α. In contrast, the eIF-2B activity was not readily inhibited in extracts from cells overexpressing either the eIF-2α 48A or 51A mutant. In addition, eIF-2B activity was decreased in extracts prepared from heat-shocked cells overexpressing wild-type eIF-2α, whereas the decrease in eIF-2B activity was less in heat-shocked cells overexpressing either mutant 48A or mutant 51A. While the phosphorylation at serine 51 in eIF-2α impairs the eIF-2B activity, we propose that serine 48 acts to maintain a high affinity between phosphorylated eIF-2α and eIF-2B, thereby inactivating eIF-2B activity. These findings support the hypothesis that phosphorylation of eIF-2α inhibits protein synthesis directly through reducing eIF-2B activity and emphasize the importance of both serine 48 and serine 51 in the interaction with eIF-2B and regulation of eIF-2B activity.
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    Inhibition of protein synthesis in insect cells by baculovirus-expressed heme-regulated eIF-2α kinase
    ( 1994-10-14) Chefalo, Peter J. ; Yang, Jane M. ; Ramaiah, Kolluru V.A. ; Gehrke, Lee ; Chen, Jane Jane
    To study further the regulation of the heme-regulated eIF-2α kinase (HRI), we have produced functional wild type HRI using the baculovirus expression system. The amount of recombinant HRI protein expressed in insect cells is approximately 10 times higher than levels in reticulocytes. Baculovirus-expressed HRI (BV-HRI) is indistinguishable from HRI purified from rabbit reticulocytes. It is active both as an autokinase and an eIF-2α kinase. BV-HRI is regulated by heme in vitro as well as in intact insect cells. Coexpression of the wild type HRI with the inactive K199R HRI, S51A eIF-2α, or interleukin-1β (IL-1β) results in diminished expression of these proteins. Expression of wild type HRI also results in severe inhibition of general protein synthesis in Sf9 cells when compared with cells expressing K199R HRI or IL-β. In addition, the guanine nucleotide exchange activity of eIF-2B is suppressed in Sf9 cells expressing wild type HRI but not in cells expressing the K199R HRI or IL-1β. Furthermore, expression of wild type HRI is increased by coexpression with the nonphosphorylatable S51A eIF-2α or by the addition of hemin, which inhibits HRI activity. These results provide evidence that translational regulation by phosphorylation of eIF-2α and sequestration of eIF-2B can operate in insect cells.
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    Phosphorylation of wheat germ initiation factor 2 (eIF-2) by N- ethylmaleimide-treated wheat germ lysates and by purified casein kinase II does not affect the guanine nucleotide exchange on eIF-2
    ( 1995-01-01) Janaki, Narahari ; Krishna, Vattem M. ; Ramaiah, Kolluru V.A.
    Phosphorylation of the small subunit of eukaryotic initiation factor-2 (eIF-2α) impairs protein synthesis in mammalian systems. It is not known, however, if a similar regulatory mechanism exists in plants. Previous reports indicate that one of the wheat germ eIF-2 subunits, the p40-41 doublet, is phosphorylated by heterologous eIF-2α kinases. Here we report that phosphorylation of the small subunit in wheat germ eIF-2, p36, occurs in translating wheat germ lysates which are pretreated with N-ethylmaleimide (NEM) and dithiothreitol. Also, a purified sea star casein kinase II (CKII) phosphorylates the p41-42 doublet and p36 subunits of wheat germ eIF-2. While heme-regulated eIF-2α kinase from reticulocyte lysates does not inhibit wheat germ protein synthesis, CKII and NEM are found to be inhibitory. To determine whether phosphorylation of the small subunit (p36) is the cause for protein synthesis inhibition, we have further studied the exchange of labeled GDP for unlabeled GDP in the preformed eIF-2 · [3H]GDP complex in vitro in the presence of CKII and ATP. The GDP exchange in eIF-2 GDP complex can occur without the addition of any protein factor and the exchange reaction is marginally inhibited by CKII. A 0-70% ammonium sulfate cut fraction, prepared from NEM-treated wheat germ lysate, also does not inhibit the guanine nucleotide exchange reaction. These findings suggest that the protein synthesis inhibition in these cases is not mediated by eIF-2 phosphorylation. © 1995 Academic Press, Inc.
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    Affinity purification of mannose 6-phosphate receptor proteins. Purification and partial characterisation of goat liver receptors
    ( 1996-01-01) Yerramalla, Udaya Lakshmi ; Nadimpalli, Siva Kumar
    Mannose 6-phosphate receptor (MPR) proteins designated as MPR 300 and MPR 46 have earlier been purified from some mammals on phosphomannan coupled to cyanogen bromide activated Sepharose. In a recent study, the goat liver MPR 300 has been directly purified using Sepharose-divinylsulfone-pentamannosyl phosphate matrix. In the present report, we describe the preparation of another affinity matrix Sepharose-divinylsulfone-phosphomannan and its utility in purifying the MPR proteins from goat liver. While the MPR 300 from goat liver showed an electrophoretic mobility similar to other mammalian MPRs, the small receptor showed a molecular weight of 36 kDa. Antibodies raised against goat liver MPR 300 react specifically with the large receptor protein. Additionally affinity purified peptide specific antibody corresponding to amino-acid residues 26-42 (ADGCDFVCRSKPRNVPA) of the cytoplasmic tail of the human liver MPR 46 cross-reacts with the purified small receptor.
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    Purification in high yield and characterisation of the galactose-specific lectin from the seeds of snake gourd (Trichosanthes anguina)
    ( 1996-01-01) Komath, Sneha Sudha ; Nadimpalli, Siva Kumar ; Swamy, Musti J.
    The galactose-specific lectin present in the seeds of snake gourd (Trichosanthes anguina) was purified in high yield by affinity chromatography on cross-linked guar gum. The purified snake gourd seed lectin (SGSL) yielded a single symmetrical peak on gel filtration with an M(r) of 62 kDa and gave a single band in PAGE under non-denaturing conditions. In SDS-PAGE, SGSL gave a single band of M(r) 53 kDa in the absence of β-mercaptoethanol, and two bands of M(r) 32 and 23 kDa in its presence, indicating that the lectin is a heterodimer in which the subunits are linked by a disulphide bridge. The lectin gave a single precipitin line in immunodiffusion experiments with antiserum raised against the purified SGSL. No cross-reactivity was found between SGSL and antiserum raised against the Momordica charantia lectin and vice versa, suggesting that the two lectins are antigenically dissimilar. Haemagglutination-inhibition data show that MeβD-Gal is the best monosaccharide inhibitor of SGSL and indicate that an equatorial hydroxyl at C-2 and axial hydroxyl at C-4 in the pyranose form are important binding loci for the lectin.
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    An affinity method for the purification of mannose 6-phosphate receptor proteins (MPR 215) from rat tissues and goat liver
    ( 1996-02-05) Siva Kumar, Nadimpalli
    An affinity matrix (Sepharose 6B-divinyl sulfone-pentaphosphomannan) has been developed which can be efficiently used for the purification of the MPR 215 from different tissues of rat as well as from goat liver. The matrix developed is relatively easy to prepare compared with the available procedures, and can be used for the purification of similar receptor proteins from other sources.
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    Type 1 phosphatase inhibitors reduce the restoration of guanine nucleotide exchange activity of eukaryotic initiation factor 2B in inhibited reticulocyte lysates rescued by hemin
    ( 1996-03-15) Naresh Babu, Sepuri V. ; Atchuta Ramaiah, Kolluru V.
    In heme-deficient reticulocyte lysates, the α-subunit of eukaryotic initiation factor-2 (eIF-2α) is phosphorylated due to the activation of the heme-regulated eIF-2α kinase (HRI). Phosphorylation of eIF-2α impairs the guanine nucleotide exchange activity of eIF-2B and thereby inhibits or shuts off protein synthesis. Delayed addition of hemin to shut-off lysates inhibits the eIF-2α kinase activity of HRI and restores protein synthesis; under those conditions, the endogenous phosphatase of the lysate dephosphorylates phosphorylated eIF-2α and restores eIF-2B activity. In this report we present evidence that the restoration of eIF-2B activity is dependent on the concentration of added hemin and is related to HRI activity in lysates. The recovery of eIF-2B activity is not affected by protein synthesis inhibitors such as cycloheximide, pactamycin, and puromycin, which do not affect the eIF-2α phosphorylation. Also, the functional eIF-2B activity that is available in hemin-supplemented lysates is not affected by phosphatase inhibitors such as okadaic acid and heat-stable inhibitor-2. However, the recovery of eIF-2B activity that is observed by the delayed addition of hemin to inhibited heme-deficient lysates is reduced by inhibitor-2 and high concentrations of okadaic acid. These findings suggest that a type 1 phosphatase is involved in the recovery of eIF-2B activity and protein synthesis upon delayed addition of hemin to heme-deficient lysates.
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    Affinity purification of N-acetylglucosamine specific lectins. Purification and partial characterisation of triticale lectin
    ( 1996-10-17) Nadimpalli, Siva Kumar ; Kompella, Padma
    Seeds of Triticale contain a lectin that agglutinates rabbit erythrocytes whose activity is inhibited by N-Acetylglucosamine and its oligomers. An affinity method has been developed that efficiently binds the lectin activities from Triticale seeds and wheatgerm. Purified Triticale lectin is a glycoprotein with 3% carbohydrate and migrates as a single band corresponding to Mr. 15000 on SDS-PAGE. Antibodies raised to purified wheat germ agglutinin do not cross-react with purified Triticale lectin. Leucine/Isoleucine is the only N-terminal residue in the Triticale lectin. Presence of inhibitory sugar induces spectral changes in the protein in the UV region. Triticale lectin does not agglutinate human ABO erythrocytes and does not inhibit fungal growth.
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    Purification of α-mannosidase activity from Indian lablab beans
    ( 1997-01-01) Tulasi, Rajasekhar Baru ; Nadimpalli, Siva Kumar
    Seeds of Dolichos lablab var. typicus (Indian lablab beans) contain a glucose/mannose specific lectin that was affinity purified on Sepharose mannose columns in our laboratory. The unbound fraction from this matrix showed a-mannosidase activity. In the present study this has been purified to homogeneity by a combination of ion-exchange, hydrophobic chromatography and gel filtration. Purified α-mannosidase had an apparent molecular weight of 195,000 ± 5,000 with 4.5% carbohydrate. On SDS-PAGE under reducing conditions, the enzyme dissociated into two major bands corresponding to Mr 66,000 and Mr 44,000. An antibody to the well studied jack bean α-mannosidase cross-reacts with the enzyme from the lablab beans suggesting antigenic similarity between these two legume mannosidases.
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    The effects of pyrroloquinoline quinone on heme-regulated eIF-2α kinase and eIF-2B activities in eukaryotic protein synthesis
    ( 1997-01-01) Atchuta Ramaiah, Kolluru V. ; Chen, Jane Jane ; Gallop, Paul M. ; London, Irving M.
    Pyrroloquinoline quinone (PQQ), a novel cofactor of biological redox processes, is ubiquitous in animal cells. We have examined the effects of PQQ on protein synthesis. PQQ inhibits protein synthesis in hemin-supplemented rabbit reticulocyte lysates. This inhibition is characterized by increased phosphorylation of eIF-2α and by diminished guanine nucleotide exchange activity of eIF-2B. The increased eIF-2α phosphorylation is the result of activation by PQQ of the heme-regulated eIF-2α kinase (HRI). The addition of 10 μM PQQ completely inhibits the increase in protein synthesis that occurs on the addition of hemin (20 μM) to heme-deficient lysates, whereas a lower concentration of PQQ (100 nM) causes a very slight stimulation of protein synthesis. The increased eIF-2α phosphorylation that occurs at high concentrations of PQQ inhibits eIF-2B activity, presumably due to formation of a 15S complex [eIF-2(αP)·eIF-2B] in which eIF-2B becomes non- functional. Low concentrations of PQQ (0.1-1 μM) do not affect eIF-2α phosphorylation, but rather enhance the guanine nucleotide exchange activity of eIF-2B in reticulocyte lysates. In Chinese hamster ovary cell extract which is devoid of significant eIF-2α kinase activity, addition of both low and high concentrations of PQQ results in an increase in eIF-2B activity. The addition of PQQ to reticulocyte lysates activates HRI whereas addition of PQQ to purified HRI in vitro inhibits the autokinase and eIF-2α kinase activity of the HRI; the inhibition of purified HRI by PQQ is observed both in the presence and absence of hemin. These findings suggest that PQQ inhibits purified HRI by acting as an oxidant whereas in lysates in which PQQ is readily reduced, the PQQ acts as a reductant and increases the activities of both HRI and eIF-2B.