Showing papers by "Hamish N. Munro published in 1988"
TL;DR: In this article, an electrophoretic separation procedure was used to form RNA-protein complexes involving a highly conserved sequence in the 5' untranslated region of both ferritin heavy-and light-subunit mRNAs.
Abstract: The mRNAs for the heavy and light subunits of the iron-storage protein ferritin occur in cells largely as inactive ribonucleoprotein particles, which are recruited for translation when iron enters the cell. Cytoplasmic extracts from rat tissues and hepatoma cells were shown by an electrophoretic separation procedure to form RNA-protein complexes involving a highly conserved sequence in the 5' untranslated region of both ferritin heavy- and light-subunit mRNAs. The pattern of complex formation was affected by pretreatment of rats or cells with iron. Crosslinking by UV irradiation showed that the complexes contained an 87-kDa protein interacting with the conserved sequence of the ferritin mRNA. We propose that intracellular iron levels regulate ferritin synthesis by causing changes in specific protein binding to the conserved sequence in the ferritin heavy- and light-subunit mRNAs.
587 citations
TL;DR: Vitamin C status and interactions with other nutrients were studied in 677 healthy, noninstitutionalized elderly people and plasma AA levels were significantly correlated only with plasma levels of vitamin E and folate in females.
69 citations
TL;DR: Evidence regarding the latter' supports the thesis that hemosiderin originates from ferritin that has undergone intracellular digestion of its protein shell, leaving the iron core, usually located inside the inspissated remains of secondary lysosoma1 vesicles.
Abstract: Storage of iron in the tissues occurs in the form of ferritin and hemosiderin. Evidence regarding the latter' supports the thesis that hemosiderin originates from ferritin that has undergone intracellular digestion of its protein shell, leaving the iron core, usually located inside the inspissated remains of secondary lysosoma1 vesicles. Ferritin and hemosiderin are thus components of a continuum. This paper focuses on fenitin. Ferritin has been identified in all types of living organisms: animals, plants, molds, and bacteria.2 Within the protein shell of ferritin, iron is first oxidized to the ferric state for storage as ferric oxyhydroxide. The advantage of this mechanism is that it removes excess iron from the cell sap where it could otherwise participate in peroxidation mechanisms. For example, a single parenteral dose of iron salts administered to rats has been found to result in a burst of ethane exhaled by animal^.^ This is due to peroxidation of membrane-associated omega-3-fatty acids, a response that can be suppressed by raising intake of vitamin E. Such experiments and others emphasize that iron can generate free radicals detrimental to cell membranes and to other molecular structures. Ferritin is the antidote for this phenomenon. The hollo'w protein shell of ferritin is penetrated by channels through which iron enters and exits from the ferritin cavity. The protein shell has a molecular weight of about 5 x105, and is made up of 24 subunits of two types, a slightly heavier H (mol. wt. about 21,000) and a lighter subunit L (mol. wt. about 20,000). When ferritin isolated from a tissue is subjected to isoelectric focusing, it segregates into a series of isoferritins with varying proportions of H and L subunits in the shell.4 TABLE 1 shows that the H : L ratios for isoferritins in rat tissues display a progression throughout the isofocusing gradient, suggesting that the surface charges of H and L subunits differ and their proportions thus determine the PI of the ferritin shell. It will be noted that the H : L ratios for a given isofocusing pl are quite different in rat heart and liver (TABLE 11, suggesting that the H and/or L subunits in these two tissues have different surface charges. This could be due to tissue-specific differences in primary amino acid sequences or to posttranslational modifications from glycosylation or other changes. A knowledge of the number of expressed ferritin genes could allow a decision as to which explanation is favored.
29 citations
TL;DR: In rats under a variety of conditions, label from [1-3H]galactose accumulated in glycoprotein-bound galactose much more than in acetaminophen-bound glucuronic acid, demonstrating limitation of the rate of transfer from UDP-Galactose to UDP-glucose at the epimerase step.
Abstract: A tracer methodology has been developed for noninvasive assessment of intrahepatic metabolism of administered labeled sugars. In this procedure, we measure the output of the label from the liver in two glycoconjugates derived from hepatic UDP-glucose, namely, glucuronic acid formed through UDP-glucuronic acid and excreted in the urine following acetaminophen administration, and galactose formed through UDP-galactose and then secreted in the carbohydrate portion of glycoproteins in the plasma. Comparison of the distribution of label from various sugar precursors in these end-products can indicate exchanges between hepatic UDP-glucose, UDP-galactose, and UDP-glucuronic acid. In this study we apply the technique to explore whether the enzyme UDP-galactose-4-epimerase catalyzing the step UDP-galactose to UDP-glucose is nonequilibrium and therefore potentially has a regulatory role for utilization of free galactose. The specific activity in the two glycoconjugates was compared when either (1-3H)galactose or (U-14C)glucose was the infused precursor sugar. In rats under a variety of conditions (fasting, oral refeeding, intravenous administration of galactose), label from (1-3H)galactose accumulated in glycoprotein-bound galactose much more than in acetaminophen-bound glucuronic acid, in comparison to label from (U-14C)glucose, demonstrating limitation of the rate of transfer from UDP-galactose to UDP-glucose at the epimerase step. Accordingly, epimerase is suggested to have a regulatorymore » role in the galactose assimilation pathway.« less
16 citations
TL;DR: Preterm human placentae produce insulin-like growth factor- (IGF-)specific binding protein(s) that possess a molecular weight in the 45 to 50 kD range, and in contrast, term placental tissue produced almost no detectable binding protein activity.
12 citations