Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Nutrition and Food Science, 1983. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 226-242. / by Thomas Schrager. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nutrition and Food Science, 1983. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 179-189. / by Maria Lynn Buttolph. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Nutrition and Food Science, 1983. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / by Spiros Jamas. / M.S.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Nutrition and Food Science, 1983. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Vita. / Includes bibliographical references. / by Larry Richard Brown. / Sc.D.

Thesis (Sc.D.)--Massachusetts Institute of Technology, Dept. of Nutrition and Food Science, 1984. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 146-167. / by Eric Arthur Johnson. / Sc.D.

Thesis: M.S., Massachusetts Institute of Technology, Department of Nutrition and Food Science, 1972 / Cataloged from the official PDF version of thesis. / Includes bibliographical references (pages 143-155). / Carbon recycle by means of physicochemically synthesized carbohydrates has been proposed. These artificial sugars can be used to generate single cell protein. However, it is not known what effects the unnatural components will have on the yield, productivity, and metabolic regulation of the or­ganisms used. We have obtained from natural populations, a number of organisms which utilize L-glucose as sole carbon source. Of the twelve organisms isolated, five are gram-negative aerobic rods, one is a gram positive coccus, two are thermophilic bacilli, three are yeasts, and one is a mycelial form. Pre­liminary taxonomy was done on these organisms. When fully adapted to growth on L-glucose, one pseudomonad grows ex­ponentially with a doubling time of 14 to 16 hours with 5 g/L L-glucose in the medium. Cell yields are about 0.46 g dry cells/g L-glucose, and cell densities as high as 2.8 g/L have been acheived in shake flasks. The ap­parent maximum growth rate is 0.0506 hr.⁻¹ and the apparent overall K[subscript m] for growth is 0.14 g/L L-glucose. However, substrate inhibition sets in at about 4.5 g/L L-glucose. L-glucose transport takes place by facilitated diffusion at V[subscript max] = 2.63 x 10⁻³ mg L-glucose/(mg cells-min) and K[subscript m]= 0.65 g/L L-glucose. The organism probably utilizes the entire L-glucose molecule. There is evidence that carbon 1 is eliminated as CO₂ and subsequently reassimilated from the medium. One or more growth factors appear to be necessary for L­ glucose utilization. They are made by the organism under good growth con­ditions and one appears to be excreted into the medium. A hypothetical mechanism of L-glucose utilization consistent with the growth kinetics is proposed. This mechanism involves a catabolic sequence with at least two limiting reactions. The first is incipient transport limitation and the second is inhibition by an intracellular metabolite derived from L-glucose. / by Robert C.J. Fewkes. / M.S. / M.S. Massachusetts Institute of Technology, Department of Nutrition and Food Science

Thesis: M.S., Massachusetts Institute of Technology, Department of Nutrition and Food Science, 1972 / Cataloged from the official PDF version of thesis. Vita. / Includes bibliographical references (pages 58-62). / Chapter I. Historical introduction to Vitamin B₆ Complexes. Chapter II. The aldimine complexes N(Salicylidene)glycinato and valinatozinc(II), N,~pyridoxylidene)valinatocopper(II) monohydrate and N-(3-Hydroxypyridyl-2-methylene)valinatocopper( II) hemihydrate have been prepared from L̳-valine. Synthetic methods and characterization data are given. Also prepared were the bis-chelate amino acid ester complexes, Bis[N- (2-ethoxycarbonyl-l-propyl)salicylaldiminato]copper(II) and Bis[N-(3-ethoxycarbonyl-2-propyl)salicylaldiminato]copper(II). The inertness of these two complexes to H-D exchange contrasts with the ready exchange in the absence of base of the complexes derived from a-amino acids. This result shows that facile exchange and racemization properties of Bis[N-(alkoxycarbonylalkyl)salicylaldimino] metal(II) complexes derive principally from the direct attachment of the electron-withdrawing HC=NM and COOC₂H₅ groups to the asymmetric center. The base-catalyzed racemization rates of four copper(II)-aldimine complexes in 95% ethanol at 50° were found to increase in the order N-Salicylidene-L̳-valinatocopper( II), Cu(sal-L̳-val) << N-Pyridoxylidene-L̳-valinatocopper(II) </- N-3-Hydroxypyridyl-2-methylene-L̳-valinatocopper(II) <N-4-NO₂ - Salicylidene-L̳-valinatocopper(II). This order is essentially the same as that of qualitative catalytic effectiveness of the constituent o̲-hydroxyarylcarbonyl compounds in nonenzyrnatic transamination and reinforces in semiquantitative fashion the prevailing model of ligand electronic features requisite to catalytic activity of these compounds. / by Georgia Nan Weinstein. / M.S. / M.S. Massachusetts Institute of Technology, Department of Nutrition and Food Science

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Nutrition and Food Science, 1972 / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references (pages 140-151). / Intraperitoneal administration of L-dopa {50-300 mg/kg) caused a marked disaggregation of brain polysomes in immature rats {15-20 g body weight). Polysome disaggregation was maximal between 40 and 60 minutes after injection and not significant at 20 and 120 minutes. Older rats {50 and 100 g body weight) showed a similar response, but required larger doses of the amino acid {500 mg/kg). Disaggregation could not be sustained in 100 g rats by chronic single injections of 500 mg/kg per day for 10 days; disaggregation occurred only if the last dose of L-dopa was 1 hour before·sacrifice. Polysome disaggregation after oral L-dopa was achieved in. 100 g rats if the dopa administered was very high {3 g/kg) and the time after administration was increased to 90-120 minutes. Brain polysomes may be unique in their response to L-dopa, as neither rat liver nor skeletal muscle showed a change in polysome aggregation after L-dopa injection. To determine the mechanism of L-dopa on polysome disaggregation, the metabolism of L-dopa in the brain was examined. Single i.p. doses significantly elevated tryptophan content in the brain at the three ages of rats examined; hence the effect of L-dopa on polysomes did not result from the unavailability of this amino acid. No other amino acid was depleted after L-dopa administration to account for brain polysome disaggregation. The effects of intraperitoneal L-dopa and related drugs on brain polysomes and dopa metabolism were compared in 50 g rats to determine which subsequent metabolic pathway within the brain was responsible for the polysome disaggregation. At the time after L-dopa when polysome⁻ disaggregation occurred there were increased brain dopa, 3-O-methyldopa levels and a depletion of S-adenosylmethionine. There was a four-fold increase in dopamine and a small, insignificant increase in norepinephrine. The disaggregation of brain polysomes in rats after L-dopa administration was not reproduced by administering its metabolite 3-0-methyldopa, nor by giving D-dopa. D-dopa also depleted the brain of S-adenosylmethionine, to synthesize 3-0-methyldopa, but was not converted to catecholamines. Polysome disaggregation did not take place when L-dopa was given after a decarboxylase inhibitor;. there was no increase in dopamine when L-dopa was administered after the inhibitor, although the concentration of dopa in the brain was four times the level attained with L-dopa injection alone. These experiments suggested that formation of a catecholamine was an obligatory requirement for polysome disaggregation in the brain after L-dopa. Polysome disaggregation did not occur when dopamine or norepinephrine were administered intracisternally. However, polysome disaggregation was potentiated when 100 mg/kg L-dopa, a dose that alone did not disaggregate polysomes, was given after a monoamine oxidase inhibitor. Blocking one route of catecholamine metabolism, by this inhibitor resulted in a much higher level of catecholamines in the brain than expected after this dose of L-dopa alone; the dopamine concentration was equivalent to that after 500 mg/kg L-dopa alone. These observations suggested that the mechanism by which L-dopa disaggregated brain polysomes involved its conversion to dopamine within the majority of brain cells. The responses of brain polysomes and brain tryptophan to L-dopa administration to rats were apparently unrelated, because the dose responses and time courses of these phenomenon were different. Tryptophan levels rose before and remained elevated after polysomes were disaggregated. Administration to 50 and 100 g rats of low doses of L-dopa, that could not disaggregate brain polysomes, elevated brain tryptophan content. The increase in brain tryptophan content after L-dopa occurred with a concurrent larger increase in plasma tryptophan level. The plasma tryptophan rise was not due to an alteration in plasma insulin level, nor could it be attributed to a decrease in liver or skeletal muscle tryptophan content. Except for increases in tryptophan and dopa, no plasma amino acid level was altered in rats after L-dopa. The increase in brain tryptophan content was no longer seen in 100 g rats treated with chronic single injections of 100 mg/kg per day, and if the last dose of L-dopa was one day before sacrifice, brain tryptophan content declined. / by Bette Fishman Weiss. / Ph. D. / Ph. D. Massachusetts Institute of Technology, Department of Nutrition and Food Science

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Department of Nutrition and Food Science, 1972 / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references (pages 98-107). / Daily rhythms occur in the concentrations of tryptophan in rat plasma and brain and of serotonin in rat brain. To determine whether these normally-occurring changes in plasma and brain tryptophan could account for the variation in brain serotonin, we injected rats with different doses of L-tryp­tophan and measured the responses of the plasma and brain tryptophan and the brain serotonin pools at various times after injection. A dose of 12.5 mg/kg, given at the time of day when plasma and brain tryptophan levels are normally low­est, produced elevations in plasma and brain tryptophan and in brain serotonin which approached, but did not exceed, peak daily concentrations. Thus, changes in plasma and brain try­ptophan within the normal dynamic range are capable of pro­ducing significant changes in brain serotonin levels. Because the ingestion of carbohydrate produced signifi­cant alterations in plasma and brain tryptophan and in brain serotonin, experiments were performed to test the response of these three pools to the consumption of another constituent of food, protein. Following the ingestion of the same carbohy­drate diet supplemented with casein, 18% dry weight, plasma tryptophan levels became elevated, but brain tryptophan and serotonin concentrations did not change. Inasmuch as protein contains amino acids that compete with tryptophan for trans­port into the brain, the influx of these amino acids along with tryptophan into the circulation following protein inges­tion may have produced an effective inhibition of tryptophan uptake into the brain. Thus, carbohydrate diets containing an amino acid mixture approximating casein in amino acid com­position, but lacking the amino acids thought to compete with tryptophan for transport into the brain (tyrosine, phenylalanine, leucine, isoleucine, and valine), were fed to rats. Follow- ing the ingestion of this diet, plasma and brain tryptophan and brain serotonin and 5-hydroxyindoleacetic acid levels all increased. If animals were fed the amino acid mixture diet lacking aspartate and glutamate (amino acids thought not to compete with tryptophan for transport) instead of the large neutral amino acids, or the complete amino acid mix diet (including the large neutral amino acids), plasma tryptophan concentrations rose, but no increases in brain tryptophan, serotonin, or 5-hydroxyindoleacetic acid occurred. The con­centrations of serotonin and its major metabolite in brain, which appear to be influenced by tryptophan availability to the brain, thus are subject not only to plasma tryptophan levels, but also to the levels of several other amino acids in plasma. These results support the hypothesis that the rate of serotonin synthesis in brain is influenced by tryptophan availability. They demonstrate a remarkable sensitivity of brain serotonin concentrations to changes in brain tryptophan levels within the normal dynamic range. Long-term changes in brain serotonin were also studied in rats consuming a diet containing a naturally-occurring protein very low in tryptophan content (corn protein). In these animals, the plasma and brain tryptophan pools were greatly depressed after five weeks on the diet; brain sero­tonin concentrations were correspondingly decreased. Similar results were obtained in rats eating smaller than normal quantities of a diet containing a protein with normal amounts of tryptophan. / by John Dickson Fernstrom. / Ph. D. / Ph. D. Massachusetts Institute of Technology, Department of Department of Nutrition and Food Science

Thesis: S.M., Massachusetts Institute of Technology, Department of Nutrition and Food Science, 1972 / Cataloged from the official PDF version of thesis. / Includes bibliographical references (pages 171-180). / Methods were investigated for determination of volatile nitrosamines which have been reported to occur in foods and other environmental samples. Nitrosamines were removed from foods using a Likens-Nickerson extractor; 81% of added dimethylnitrosamine and 110% of added diethylnitrosamine were recovered from 10 ng/g spiked aqueous solutions. The factors affecting recovery of these nitrosamines were investigated. The usefulness of Freon-11 as an extracting solvent for nitrosamines was investigated using both batch serial and continuous liquid-liquid extraction. Potential gas chromatographic (GC) interferences were removed from food extracts by an acid extraction step and, when needed, by liquid column chromatography on alumina and silica gel. Dilute solu­tions containing nitrosamines were analyzed directly using a GC solvent stripping technique. Nitrosamines were detected with the Coulson electrolytic conductivity detector operated in the pyrolytic mode and with a flame ionization detector. The sensitivities of these detectors were compared for selected alkyl and heterocyclic nitros­amines. The specificity of the Coulson detector was demonstrated for analysis of extracts of meat and fish samples. Additional clean-up of food extracts is re­quired to insure identification of nitrosamines by combined GC-mass spectrometry. A method employing chromatographic equilibration (frontal analysis) was investigated for determination of dimethylnitrosamine in the air. / by John Martin Essigmann. / S.M. / S.M. Massachusetts Institute of Technology, Department of Nutrition and Food Science