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Biomedical subjects

S H Zeisel

Publications and source records attributed to S H Zeisel.

107 records · Page 6Linked to original sources
PubMed1982

Neurotransmitter precursors and brain function.

Brain function can be affected by the availability of dietary precursors of neurotransmitters. This occurs because the rate-limiting synthetic enzymes are not "saturated" with substrate under normal circumstances. Tyrosine affects catecholaminergic neurons that fire rapidly, whether in the brain stem to decrease blood pressure in hypertension or in the adrenal gland to increase blood pressure in hypotension, and has been used in the treatment of Parkinson's disease and depression. Choline forms acetylcholine and has been used successfully in the treatment of tardive dyskinesia and memory disorders. Tryptophan, which forms serotonin, has been used for chronic pain therapy, sleep disorders, depression, and appetite control. Although these substances may lack the potency of traditionally used agonists, they offer an increase in specificity because the enzymes necessary to convert them to neurotransmitters are found only in neurons. Precursors are also "physiological"; they are consumed as foods and, therefore, should be relatively safe therapeutic agents.

Animals↗
PubMed1981

Developmental changes in rat blood choline concentration.

1. Serum choline concentration in the newborn rat is extremely high and declines as the rat matures until adult values are attained at 20 days of age. 2. Rat milk is a rich source of choline, and rat pups denied access to milk had significantly lower serum choline concentrations than did fed littermates. We conclude that dietary intake of choline contributes to the maintenance of high serum choline concentrations in the neonatal rat. 3. In vivo, choline disappears with a half-life of 70 min. It is converted into betaine, phosphocholine and phosphatidylcholine. The rate of phosphocholine formation is identical in 3- and 10-day-old rats (3.3 mumol/h), whereas the rate of betaine formation is slower in younger animals (0.15 mumol/h at 3 days versus 0.69 mumol/h at 10 days). In vitro, choline oxidase activity [choline dehydrogenase (EC 1.1.99.1) and betaine aldehyde dehydrogenase (EC 1.2.1.8)] increased between birth and 40 days of age. The age-related acceleration in choline's conversion into betaine probably tends to diminish unesterified choline concentration in the rat.

Aging↗
PubMed1981

Developmental changes in brain indoles, serum tryptophan and other serum neutral amino acids in the rat.

The rates at which brain neurons synthesize and release serotonin depend in part on brain tryptophan concentrations; these, in turn, vary directly with serum (or plasma) tryptophan, and inversely with the serum concentrations of other large neutral amino acids (LNAA). Concentrations of serum tryptophan, LNAA and brain indoles were examined in samples drawn at noontime from rats aged 0-59 days. Developmental changes in serum tryptophan largely paralleled those in the tryptophan/LNAA ratio, and brain tryptophan concentrations. Brain serotonin and 5-hydroxyindole acetic acid (5-HIAA) levels also increased postnatally; the changes in 5-HIAA tended to parallel those in brain tryptophan while those in serotonin did not.

Aging↗
PubMed1981

Effects of ingesting soy or egg lecithins on serum choline, brain choline and brain acetylcholine.

Rats were fed lecithins, derived from eggs or soybeans, to determine whether the fatty acid composition of the phosphatidylcholine altered choline availability. Rats were fed either a single meal containing 5 g phosphatidylcholine or a lecithin-containing diet for 3 weeks, including approximately 5 g phosphatidylcholine per day. Each form of dietary lecithin elevated blood choline, brain choline and brain acetylcholine significantly (P < 0.05). There was no difference in response to egg- or soy-derived lecithin.

Acetylcholine↗
PubMed1980

Prenatal diagnosis of neural tube defects. V. The value of amniotic fluid cholinesterase studies.

Total cholinesterase activity in amniotic fluid obtained from 150 fetuses was measured. Elevated values were found in 94% of samples from fetuses known to have neural tube defects (spina bifida, anencephaly) when compared to nonbloody samples from normal fetuses. Contamination of amniotic fluid with blood was observed to elevate total cholinesterase activity in some, but not all, such specimens. Total cholinesterase activity did not vary with gestational age between 15 and 24 weeks. These data were compared to our large alpha-fetoprotein (AFP) assay experience used for the prenatal detection of neural tube defects. We concluded that the assay of total cholinesterase activity in amniotic fluid could be a useful adjunct to the AFP assay, especially in those samples contaminated with blood.

Amniotic Fluid↗
PubMed1980

Uptake of free choline by isolated perfused rat liver.

The uptake of free choline by isolated perfused rat liver was characterized. A saturable uptake mechanism [Ka = 0.17 +/- 0.07 mM (SD); Vmax = 0.84 +/- 0.16 mumol/min X g dry weight] and a nonsaturable mechanism (through which uptake is proportional to choline concentration in the perfusate) were identified. Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin. Free choline also accumulated within the intracellular space, suggesting that choline oxidase activity does not always limit choline's uptake by the liver.

Animals↗
PubMed1980

Normal plasma choline responses to ingested lecithin.

We examined plasma choline changes after ingestion of diets composed of common foodstuffs, with choline contents bracketing the average daily intake in the American diet, and ingestion of diets supplemented with exogenous purified lecithin. A diet with low choline content did not increase plasma choline concentrations; a diet with high choline content doubled plasma choline levels. A lecithin-supplemented (25 gm; 80% phosphatidylcholine) low-choline diet increased plasma choline levels 400%. These findings indicate that normal diets cause only small elevations in plasma choline; purified lecithin supplements are likely to have greater effects in treating neurologic diseases.

Adolescent↗
PubMed1979

Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain.

Choline molecules are needed for the synthesis of acetylcholine and phospholipids in the mammalian brain. An enzymatic activity capable of forming lecithin (phosphatidylcholine) from the step-by-step methylation of phosphatidylethanolamine is identified in the bovine brain. This enzyme(s), phosphatidylethanolamine-N-methyltransferase (EC 2.1.1.17), is localized in the synaptosomal fraction of bovine caudate nucleus, uses S-adenosylmethionine as the methyl donor (apparent Km = 20 micrometers), and has a Vmax of 50--60 pmol/mg protein X h (i.e. about 1% of that found in rat liver). The brain may be able to meet some of its choline requirements by de novo synthesis.

Animals↗
PubMedDate not supplied

Assessing effects of serotonin precursors on newborn behavior.

While traditional studies of newborn diet have focused on the effects of malnutrition on the central nervous system, there is now interest in how qualitative differences in the composition of early newborn feeding might influence behavior. This paper reviews the available techniques for assessing newborn perception and cognition, as well as behavioral organization. The paper then focuses intensively on measures of newborn state behaviour in view of evidence in adult humans, as well as in non-human species, suggesting a relationship between sleep behavior (sleep onset, night waking) and brain serotonin levels. A study designed to examine the relationship between dietary precursors of brain serotonin (within the range of concentrations found in human milk) and newborn state behavior after feeding is described to illustrate the application of these techniques. Healthy, fullterm newborns were fed a modified formula, containing tryptophan or valine, on one day, a routine formula on another day, and observed continuously for 3 h after each feeding for the observation and recording of newborn state. Data from individual infants in the tryptophan and valine groups are presented to illustrate the findings that infants fed tryptophan entered quiet sleep and active sleep sooner than infants fed valine and spent more time in active sleep and less time alert. These results illustrate the value of newborn behavior as a sensitive dependent variable in studies of behavioral effects of diet and suggests that variations in serotonin levels in the newborn brain may modulate the newborn's sleep/wake behaviour.

Brain Chemistry↗
PubMedDate not supplied

Choline: an essential dietary nutrient?

Choline (trimethyl-beta-hydroxyethylammonium) is a quaternary amine which is widely distributed in plants and animals. It contains three methyl groups which are important in a number of metabolic reactions, including the synthesis of methionine and carnitine. Choline is also a component of the phospholipids phosphatidylcholine and sphingomyelin, important constituents of all cell membranes. Finally, choline is necessary for the synthesis of the neurotransmitter acetylcholine. Although this compound is considered an essential nutrient in numerous mammalian species, this has not been established for humans.

Animal Nutritional Physiological Phenomena↗