There are a number of components present in soybeans that exert a negative impact on the nutritional quality of the protein. Among those factors that are destroyed by heat treatment are the protease inhibitors and lectins. Protease inhibitors exert their antinutritional effect by causing pancreatic hypertrophy/hyperplasia, which ultimately results in an inhibition of growth. The lectin, by virtue of its ability to bind to glycoprotein receptors on the epithelial cells lining the intestinal mucosa, inhibits growth by interfering with the absorption of nutrients. Of lesser significance are the antinutritional effects produced by relatively heat stable factors, such as goitrogens, tannins, phytoestrogens, flatus-producing oligosaccharides, phytate, and saponins. Other diverse but ill-defined factors appear to increase the requirements for vitamins A, B12, D, and E. The processing of soybeans under severe alkaline conditions leads to the formation of lysinoalanine, which has been shown to damage the kidneys of rats. This is not generally true, however, for edible soy protein that has been produced under milder alkaline conditions. Also meriting consideration is the allergenic response that may sometimes occur in humans, as well as calves and piglets, on dietary exposure to soybeans.

Implications of antinutritional components in soybean foods

PERHAPS no family of chemotherapeutic agents has been so rapidly accepted as a major therapeutic tool in treating patients with cancer as have the anthracyclines. Since the first clinical trials of...

The anthracycline antineoplastic drugs.

The antineoplastic agent adriamycin was coupled to an insoluble agarose support This material was actively cytotoxic to L1210 cells in culture under conditions in which no free adriamycin could enter the cell It is concluded that an agent whose principal target was previously thought to be DNA can exert its cytotoxic action solely by interaction at the cell surface

http://science.sciencemag.org/content/sci/217/4556/248.full.pdf

The anticancer agent adriamycin can be actively cytotoxic without entering cells

Autophagy is a conserved intracellular pathway that delivers cytoplasmic contents to lysosomes for degradation via double-membrane autophagosomes. Autophagy substrates include organelles such as mitochondria, aggregate-prone proteins that cause neurodegeneration and various pathogens. Thus, this pathway appears to be relevant to the pathogenesis of diverse diseases, and its modulation may have therapeutic value. Here, we focus on the cell and molecular biology of mammalian autophagy and review the key proteins that regulate the process by discussing their roles and how these may be modulated by posttranslational modifications. We consider the membrane-trafficking events that impact autophagy and the questions relating to the sources of autophagosome membrane(s). Finally, we discuss data from structural studies and some of the insights these have provided.

Mammalian Autophagy: How Does It Work?

I. Introduction.- II. Ribosomal Genes.- II. 1. Definitions.- II.2. Ribosomal RNA Genes.- II.2.1. Multiplicity.- II.2.2. Chromosomal Location.- II.2.3. Extrachromosomal rRNA Genes.- II.2.4. Organization and Structure.- II.2.4.1. Saccharomyces cerevisiae.- II.2.4.2. Tetrahymena.- II.2.4.3. Drosophila.- II.2.4.4. Xenopus laevis.- II.2.4.5. Higher Plants.- II.2.4.6. Mammalia.- II.2.5. General Features.- II.3. 5 S rRNA Genes.- II.3.1. Number and Chromosomal Location.- II.3.2. Organization and Structure.- II.4. Ribosomal Protein Genes.- II.5. Synopsis.- III. Transcription of Ribosomal Genes.- III. 1. Components of the Transcription Complex.- III. 1.1. RNA Polymerases.- III. 1.2. Nucleolar rDNA and r-Chromatin.- III.2. The Transcription Process >.- III.2.1. Topology of Primary Pre-rRNA.- III.2.2. Morphology of Transcribed rRNA Genes.- III.2.3. Transcribed and Non-Transcribed r-Chromatin.- III.2.4. Primary Transcripts and Primary Pre-rRNA.- III.2.5. Transcription Initiation and Termination.- III.2.5.1. Initiation.- III.2.5.2. Termination.- III.2.6. Transcription in vitro.- III.3. Transcription of 5 S rRNA Genes.- III.4. Transcription of r-Protein Genes.- III.5. Synopsis.- IV. Maturation of Preribosomes.- IV. 1. Structure of Primary Pre-rRNA.- IV. 1.1. Size and Primary Structure.- IV. 1.2. Modifications.- IV. 1.3. Conformation.- IV.2. Pre-rRNA Maturation Pathways.- IV.2.1. General Considerations.- IV.2.2. Common Pattern of Pre-rRNA Maturation.- IV.2.3. Multiplicity of Maturation Pathways.- IV. 2.4. Enzyme Mechanisms.- IV. 3. Preribosomes: Structure and Maturation.- IV. 4. Synopsis.- V. Molecular Architecture of the Nucleolus.- V. 1. Introduction.- V.2. Nucleolus Organizer.- V. 2.1. Chromosomes.- V.2.2. Interphase Nuclei.- V.3. Fibrillar and Granular Components.- V.3.1. The Fibrillar Component.- V.3.2. The Granular Component.- V.4. The Nucleolus and Other Nuclear Structures.- V.4.1. Nucleolus-Associated Chromatin.- V.4.2. The Junction with the Nuclear Envelope.- V.5. The Nucleolar Matrix.- V.6. Macromolecular Constituents.- V.6.1. DNA and RNA.- V. 6.2. Nucleolar Proteins.- V.6.2.1. General.- V.6.2.2. Ag-NOR Protein(s).- V. 6.2.3. Nucleolar Antigens.- V. 7. Outline.- VI. Regulation.- VI. l. General Considerations.- VI.2. Transscriptional Control.- VI. 2.1. Transitions in the State of Expression of rRNA Genes.- VI. 2.1.1. Inactive r-Chromatin.- VI.2.1.2. Potentialy Active and Transcribed rRNA Genes.- VI.2.2. Control of Transcription Rate.- VI.2.2.1. Role of RNA Polymerase I.- VI.2.2.2. Supply of Nucleoside-5'-Triphosphates...- VI.2.2.3. Role of Protein Synthesis.- VI.3. Posttranscriptional Control.- VI.3.1. Synthesis and Supply of r-Proteins.- VI.3.2. The Role of Pre-rRNA Structure.- VI.3.3. The Role of 5 S rRNA.- VI.3.4. Critical Control Sites.- VI.3.4.1. Alternative Processing Pathways and Intranuclear Degradation of Preribosomes and Ribosomes.- VI.3.4.2. Release From the Nucleolus and Nucleo- Cytoplasmic Transport of Ribosomes.- VI.3.4.3. Turnover of Ribosomes.- VI.4. Autogeneous Regulation of Ribosome Biogenesis in Eukaryotes: A Model.- VI.5. Synopsis.- VII. Ribosome Biogenesis in the Life Cycle of Normal and Cancer Cells.- VII. 1. Nucleologenesis and Nucleololysis.- VII. 1.1. Nucleoli and Ribosome Biogenesis During the Mitotic Cycle.- VII. 1.2. Nucleologenesis.- VII. 1.3. Nuclyeololysis.- VII.2. Inhibition of Ribosome Biogenesis.- VII.2.1. Inhibitors Interacting With DNA and Chromatin.- VII.2.2. Inhibitors That Act on RNA Polymerases.- VII.2.3. Inhibitors of Nucleoside-5'-Triphosphate Formation.- VII.2.4. The Effects of Analogues Incorporated into Polyribonu- cleotide Chains.- VII.2.5. Inhibitors of Protein Synthesis.- VII.2.6. Interpretation of Nucleolar Alterations.- VII.2.6.1. Nucleolar Segregation.- VII.2.6.2. Nucleolar Spherical Bodies and Perichromatin Granules.- VII.2.6.3. Microspherules.- VII.2.6.4. Nucleolar Fragmentation.- VII.3. Growth Transitions.- VII.3.1. Modulation of Growth Rates in Yeasts.- VII.3.2. Activation of Lymphocytes.- VII.3.3. Growth Stimulation of Cultured Cells.- VII.3.4. Differentiation of Myoblasts in Culture.- VII.3.5. Regeneration of Rat Liver.- VII.4. Senescent and Cancer Cells.- VII.4.1. Senscent Cells and Tissues.- VII.4.2. Cancer Cells.- VII.5. Synopsis.- References.

The nucleolus and ribosome biogenesis

Effects of adriamycin on surface properties of sarcoma 180 ascites cells

Inhibitors of protein synthesis capable of differential effects on nascent peptide synthesis on membrane-bound and free polyribosomes were employed to investigate the structure and function of cellular membranes of liver. The formation of membranous whorls in the cytoplasm and distension of nuclear membranes were induced by inhibitors of protein synthesis (i.e., cycloheximide and emetine) which predominantly interfere with nascent peptide synthesis on membrane-bound polyribosomes in situ. Other inhibitors of protein synthesis such as puromycin and fusidic acid, which inhibit nascent peptide synthesis on both free and membrane-bound polyribosomes, and chloramphenicol, which inhibits mitochondrial protein synthesis, did not induce these alterations. Cycloheximide, puromycin, and chloramphenicol produce some common cellular lesions as reflected by similar alterations in morphology, such as swelling of mitochondria, degranulation of rough endoplasmic reticulum, and aggregation of free ribosomes. The process of whorl formation in the cytoplasm, the incorporation of [3H]leucine and of [3H]choline into endoplasmic reticulum and the total NADPH-cytochrome c reductase activity of the endoplasmic reticulum were determined. During maximum formation of membranous whorls, [3H]leucine incorporation into cytoplasmic membranes was inhibited, while [3H]choline incorporation into these structures was increased; maximum inhibition of protein synthesis and stimulation of choline incorporation into endoplasmic reticulum, however, preceded whorl formation. Cycloheximide decreased the activity of NADPH-cytochrome c reductase of rough endoplasmic reticulum, but increased NADPH-cytochrome c reductase activity of smooth endoplasmic reticulum. In addition, cycloheximide decreased the content of hemoprotein in both the microsomal and mitochondrial fractions of rat liver, and the activities of mixed function oxidase and of oxidative phosphorylation were impaired to different degrees. Succinate-stimulated microsomal oxidation was also inhibited. The possible mechanisms involved in the formation of membranous whorls, as well as their functions, are discussed.

https://rupress.org/jcb/article-pdf/62/1/20/1386896/20.pdf

Production of membrane whorls in rat liver by some inhibitors of protein synthesis

A quantitative spectrophotometric method capable of ascertaining the rate and extent of cell agglutination resulting from the interaction of surface receptors and plant lectins has been developed. The technique measures both the rate of change in absorbance at 546 nm of suspensions of single cells which results from lectin-induced agglutination and sedimentation of cellular aggregates and a characteristic lag period preceding agglutination under carefully regulated conditions. These parameters were both influenced by: ( a ) the extent of lectin binding; ( b ) the initial concentration of single cells and the size of the various aggregates formed; and ( c ) enzymatic proteolysis and the presence of haptenic monosaccharides. The spectrophotometric assay was found to be capable of detecting surface differences between the plasma membranes of Sarcoma 180 and its 6-thiopurine-resistant variant, Sarcoma 180/TG.

https://cancerres.aacrjournals.org/content/canres/34/12/3396.full.pdf

A quantitative spectrophotometric method to measure plant lectin-induced cell agglutination.

Summary Urethan, a hepatocarcinogen in adult regenerating liver, was administered to rats at various intervals after partial hepatectomy to determine the effect of this drug on ( a ) the pattern of DNA replication and ( b ) the induction by partial hepatectomy of some enzymes required for DNA synthesis. A single i.p. dose of urethan, 1 mg/g, was injected into rats at either 0.5, 12, or 24 hr after surgery. When urethan was given 0.5 hr after partial hepatectomy, the initiation of DNA synthesis was delayed by 6 hr, followed by greater uptake of thymidine- 3 H into nuclear DNA than into that of untreated regenerating liver. When urethan was given 12 hr after partial hepatectomy, the first wave of DNA synthesis was suppressed by 50 to 60%; the second cycle of DNA replication was essentially unaffected. Administration of urethan 24 hr postsurgery resulted in maximum inhibition at 14 hr after treatment; the incorporation of thymidine- 3 H during the second wave of DNA replication occurred within a shorter period of time than that of the control. The induction of certain enzymes linked to DNA replication during liver regeneration was affected by the urethan in a similar manner. Ribonucleoside diphosphate reductase and thymidine kinase were sensitive to urethan treatment, while DNA polymerase activity was insensitive. Other enzymes not tightly coupled to DNA synthesis in regenerating liver, such as adenine and hypoxanthine-guanine phosphoribosyltransferases, were not affected by the carcinogen. The results indicate that urethan selectively inhibits the induction by partial hepatectomy of enzymes necessary for DNA synthesis.

https://cancerres.aacrjournals.org/content/canres/33/9/2149.full.pdf

The Effect of Urethan on the Incorporation of Thymidine-3H into DNA and the Activities of Some Enzymes Required for DNA Biosynthesis in Rat Regenerating Liver

Kou M. Hwang

Papers

Effects of adriamycin on surface properties of sarcoma 180 ascites cells

Production of membrane whorls in rat liver by some inhibitors of protein synthesis

A quantitative spectrophotometric method to measure plant lectin-induced cell agglutination.

The Effect of Urethan on the Incorporation of Thymidine-3H into DNA and the Activities of Some Enzymes Required for DNA Biosynthesis in Rat Regenerating Liver

Sequential biochemical events related to DNA replication in the regenerating rat liver.