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Professor Emeritus, Iowa State University, 1301 Crestridge Court, Nashville, TN 37221-4336 and * Department of Food and Beverage Technology, Procter & Gamble, Miami Valley Laboratory, Cincinnati, OH 45253-8707
1To whom correspondence should be addressed. E-mail: pbswan{at}bellsouth.net.
LaVell Henderson made important scientific and administrative contributions to nutritional science and biochemistry over a long and productive career. In particular, he contributed substantially to understanding of the metabolism of two vitamins, niacin and vitamin B-6, the amino acids tryptophan, lysine and hydroxylysine, and the elucidation of carnitine biosynthesis in mammalian cells. He also chaired two biochemistry departments. He was an active member of the American Institute of Nutrition over much of this career; he was elected a member of the AIN in 1958, a councilor in 1973 and president-elect in 1976, serving as president in 1977–1978. In 1970 he received the society’s Borden Award and was made a fellow of the society in 1986.
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University of Wisconsin |
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 TOP University of Wisconsin University of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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In May 1943 LaVell was transferred to England as a nutrition officer where he taught sanitation and nutrition to medical personnel. Later he was stationed near Paris where he continued to teach and also supervised French gardeners in raising vegetables for the allies in the formal gardens of the Chateau Le Marais. They were so successful that they were able to supply some vegetables to Parisian markets!
In January 1946 LaVell returned to Madison, where he was joined by Maurine, and completed studies for a Ph.D. in 1947. His doctoral research included exploration of the tryptophan-niacin relationship, investigations of amino acid imbalances and the development, with Esmond Snell, of methods for microbiological assay of amino acids. Much of this work was funded in part by the Nutrition Foundation. Publications from his doctoral work were largely in the Journal of Biological Chemistry, but included at least two papers in The Journal of Nutrition.
Elvehjem organized his very large research group so that more experienced students supervised the newer students and LaVell remained in Wisconsin a year after completing the doctorate to continue helping Elvehjem in the supervisory responsibilities. The following year he accepted a position as assistant professor in the chemistry department at the University of Illinois-Urbana. When he left Wisconsin, he had more than 20 scientific publications to his credit.
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University of Illinois |
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TOPUniversity of WisconsinUniversity of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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Further studies indicated that riboflavin deficiency would interfere with the conversion of kyneurinine, a known product of T, to HAA and that vitamin B-6 was required for the metabolism of T. The group began to use radioisotopes to trace the fate of carbons and hydrogen in the pathway, using (and often synthesizing) T labeled in several different positions. They also made the important observation that the very high activity of picolinate carboxylase in cats shunts HAA into an oxidative pathway rather than the pathway for conversion to niacin (1). Thus, cats cannot use T as a source of niacin, whereas humans have a limited capacity to do so, and rats very efficiently use T or HAA as a niacin source.
Henderson’s Illinois group also continued explorations begun at Wisconsin of amino acid imbalance effects, both on the conversion of T to niacin and on the use of T for protein synthesis. High dietary levels of the branched-chain amino acids or lysine interfered with the conversion of T to niacin, presumably by increasing the demand for T in protein synthesis.
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Oklahoma State University |
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TOPUniversity of WisconsinUniversity of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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Henderson’s Oklahoma research group continued the lines of work that he had established at Illinois. Using T labeled in various carbon and hydrogen atoms, they traced the details of the pathways whereby it is either converted to niacin or oxidized for energy. They followed the formation of HAA, glutaric acid and acetate from the benzene ring of T in the rat and isolated, purified and described the properties of the HAA oxidase. They demonstrated that T could be converted to niacin by chicks, guinea pigs and hamsters, but not in corn or tobacco plants, and began to explore the enzymatic conversion of QA to nicotinic acid mononucleotide (NMN) in rat liver (2).
While in Oklahoma, Henderson’s group began work on the metabolism and function of hydroxylysine. These first studies were in Streptococcus fecalis, where they demonstrated cell stability functions.
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University of Minnesota |
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TOPUniversity of WisconsinUniversity of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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A decade later, Henderson resigned as department head and took a sabbatical leave to work at the University of California-Berkeley with Esmond E. Snell, a former colleague from their days at Wisconsin. Returning to Minnesota in 1975 and continuing to teach full-time, he also assumed the half-time position of associate dean in the College of Biological Sciences, a position he held until 1984. Recognizing the paucity of positions within academia during the early 1980s, he retired at age 67 saying that he wanted to make room for younger scientists.
Throughout his 20 years at Minnesota, Henderson maintained an active research group, continuing some of the lines of work begun in Illinois and Oklahoma, but also branching out into several new lines of inquiry. Studies of amino acid balance and the requirement of amino acids for protein synthesis were moved to the isolated perfused rat liver and into in vitro systems. It was demonstrated that the omission of any one of a series of amino acids from the mixture being supplied for protein synthesis would reduce protein synthesis as measured by the extent of the aggregation of the ribosomes (3).
Investigations into the metabolism of the 4 stereoisomers of hydroxylysine continued in microorganisms and were begun in rats (4) and perfused rat liver. The D-isomers were not metabolized by liver, whereas the L-isomers were oxidized to CO2 via glutaryl-CoA. Hydroxylysine degradation began with phosphorylation of the hydroxyl group of both L-isomers by a GTP-requiring enzyme, whereas investigations of lysine degradation resulted in the conclusion that in rat liver it began with formation of saccharopine from lysine and 
-keto-glutarate. The pathway for hydroxylysine degradation in Pseudomonas fluorescens, however, differed from that in rat liver. Phosphorylated hydroxylysine was shown to be converted to 2-amino-adipic acid by a pyridoxal phosphate–requiring enzyme, with the intermediate semialdehyde converted to the acid by a NAD-requiring dehydrogenase. Glutaryl CoA, an intermediate in the degradation of T, lysine and hydroxylysine, was shown to be degraded via a dehydrogenase that formed carbon dioxide and crotonyl coenzyme A (5).
Following LaVell’s return from his sabbatical leave in 1975, his research group worked on the elucidation of carnitine biosynthesis from lysine and methionine in mammalian cells. They showed that 
-N-trimethyl-lysine was hydroxylated, via an iron and vitamin C requiring enzyme, to form ß-hydroxy--N-trimethyllysine, which underwent aldo cleavage, resulting in the formation of glycine and trimethyl-aminobutyraldehyde and then oxidation to form 4-N-trimethyl-aminobutyric acid (6). This compound, when hydroxylated, formed carnitine. Carnitine was taken up and acetylated by intestinal cells in a process in which the L-isomer was absorbed twice as rapidly as the D-isomer (7). The L-isomer was also taken up and acetylated by erythrocytes, whereas the D-isomer was not metabolized. Acetylation in the urine occurred in 40% of the L-isomer, but none of the D-isomer.
When Henderson’s group examined the metabolism of the various forms of vitamin B-6, they found that they were handled differently by different tissues. The liver took up the aldehyde, alcohol and amine forms and phosphorylated them. The only form it released was pyridoxal itself. This was the form used by the other tissues and its uptake was aided by subsequent phosphorylation and binding to protein (8). In the blood, the concentration ratio between erythrocytes and plasma was dependent upon the tighter binding of pyridoxal to hemoglobin compared with albumin. Pyridoxal was absorbed by passive diffusion from the small intestine, with hydrolization of the phosphate ester occurring in the lumen before absorption (9).
In looking at pyridine nucleotide precursors, they found that the acid form of the vitamin was a better precursor than the amide form. At physiologic concentrations of nicotinic acid, it was the sole precursor of NMN and NAD and methylated compounds were the major products from nicotinamide. However, when high levels of nicotinamide were presented to the liver, the compound was deaminated to some extent and nicotinic acid mononucleotide was formed and then converted to NMN. The amide form was absorbed more rapidly from the intestinal lumen, but the acid form was taken up more rapidly from the blood that perfused the intestine.
In collaboration with the head resident from neurosurgery, the group aided in the demonstration that serotonin on the outside of arteries in the brain was a strong vasoconstrictor. Thus, when hemorrhaging occurred in the brain, serotonin was released from the blood platelets, resulting in a cerebral arterial spasm and loss of oxygen to parts of the brain (10). They went on to investigate ways to block this life-threatening process.
It has been said of Henderson that he had a rare ability to identify significant metabolic questions, form a hypothesis as to the answer and design an elegant experiment to test that hypothesis. The long list of his noteworthy publications and the research success of his well-trained students attest to the validity of this statement.
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Service to the profession |
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TOPUniversity of WisconsinUniversity of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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At the University of Minnesota, LaVell served on several important university committees, including one that advised the university on its responses to the fiscal crisis of the early 1970s. He also represented the university on the Hormel Institute Board.
Nationally, he served for several years on the Council of the AIN, as well as serving as president of that society. He also served several terms on the editorial board of The Journal of Nutrition, one of which stretched into his retirement. For 6 years he was a member of the Food and Nutrition Board of the NRC and several of its ad hoc committees.
One large responsibility that he took very seriously was chairing the Nutrition Study Section at the NIH. This involved many hours during which he carefully reviewed the stacks of proposals that came before each meeting, time that he always found among his many other responsibilities. After his retirement, he served on the NIH Study Section on Chemical Pathology. He served on the Nutrition Training Committee and the Research Career Development Award Committee of the Institute of General Medical Sciences and provided similar consulting for the National Science Foundation, the Office of Education and the Thrasher Foundation.
LaVell was a dedicated teacher who took this responsibility very seriously. Beginning with his undergraduate teaching assistantship at Utah State University, he continued to teach throughout his professional career, although he had heavy administrative duties at times. Even in retirement, for 5 years he volunteered as a science enrichment teacher in two Salt Lake City elementary schools. Many of his over 50 undergraduate, graduate and postdoctoral advisees have made important scientific and professional contributions within academia and private industry.
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Awards and recognition |
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TOPUniversity of WisconsinUniversity of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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LaVell was described by his colleagues as "a first class gentleman." He was admired for his honesty and the great integrity that he exhibited in his work. He held high standards for himself and for others and was valued by his graduate students, postdoctoral students and junior faculty members for the care he took in helping to guide their careers.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: HAA, 3-hydroxy-anthranilic acid; NMN, nicotinic acid mononucleotide; QA, quinolinic acid; T, tryptophan.
Manuscript received 18 August 2003.
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LITERATURE CITED |
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TOPUniversity of WisconsinUniversity of IllinoisOklahoma State UniversityUniversity of MinnesotaService to the professionAwards and recognitionRetirement yearsLITERATURE CITED |
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1. Suhadolnik, R. J., Stevens, C. O., Decker, R. H., Henderson, L. M. & Hankes, L. V. (1957) Species variation in the metabolism of 3-hydroxyanthranilate to pyridine carboxylic acids. J. Biol. Chem. 228:973-982.
2. Gholson, R. K., Uedo, I., Ogasawara, N. & Henderson, L. M. (1954) The enzymatic conversion of quinolinate to nicotinic acid mononucleotide in mammalian liver. J. Biol. Chem. 239:1208-1214.
3. McGown, E., Richardson, A. C., Henderson, L. M. & Swan, P. B. (1973) Effect of amino acids on ribosome aggregation and protein synthesis in perfused rat liver. J. Nutr. 103:109-116.
4. Polan, C. E., Smith, W. G., Ng, C. Y., Hammerstedt, R. H. & Henderson, L. M. (1967) Metabolism of hydroxylysine by rats. J. Nutr. 91:143-150.
5. Besrat, A., Polan, C. E. & Henderson, L. M. (1969) Mammalian metabolism of glutaric acid. J. Biol. Chem. 244:1461-1467.
6. Henderson, L. M., Nelson, P. J. & Henderson, L. (1982) Mammalian enzymes of trimethyllysine conversion to trimethylaminobutyrate. Fed. Proc. 41:2843-2847.[Medline]
7. Gross, C. J., Henderson, L. M. & Savaiano, D. A. (1986) Uptake of L-carnitine, D-carnitine, and acetyl-L-carnitine by isolated guinea-pig enterocytes. Biochim. Biophys. Acta 886:425-433.[Medline]
8. Ink, S. L. & Henderson, L. M. (1984) Vitamin B6 metabolism. Annu. Rev. Nutr. 4:455-470.[Medline]
9. Mehansho, H., Hamm, M. W. & Henderson, L. M. (1979) Transport and metabolism of pyridoxal and pyridoxal phosphate in the small intestine of the rat. J. Nutr. 109:1542-1551.
10. Allen, G. S., Henderson, L. M., Chou, S. N. & French, L. A. (1974) Cerebral arterial spasm. 2. In vitro contractile activity of serotonin in human serum and CSF on the canine basilar artery, and its blockage by methylsergide and phenoxybenzamine. J. Neurosurg. 10:442-450.
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