The In Vivo Sparing of Methionine by Cysteine in Sulfur Amino Acid Requirements in Animal Models and Adult Humans

Abstract

Sulfur amino acid metabolism has been receiving increased attention because of the link to chronic diseases such as cardiovascular disease, Alzheimer's disease, and diabetes. In addition, the role of cysteine and optimal intakes for physiological substrates such as glutathione are currently of considerable interest in human health. Although the dietary indispensability of methionine is not in question, the ability of cysteine to substitute for a portion of its requirement has been the topic of much debate. Methionine is often the most limiting amino acid in the diets of the developing world's population because of its low concentration in cereal grains. Therefore, the ability of cysteine to substitute for methionine requirement is not just biologically interesting; it is also of considerable economic and social importance. The primary goal of this review is to discuss the available evidence on the effect of cysteine substitution for methionine to meet the total sulfur amino acid requirement in adult humans, including an assessment of the methodological features of experiments with conflicting results. Assessment of the requirement experiments for amino acids with complex metabolism such as methionine and cysteine must begin with a careful definition of requirements and what substitution means. As a result of these definitions, a set of criteria for the intakes of methionine that will allow demonstration of the substitution effect have been developed. Some recent publications are assessed using these definitions and criteria, and a possible reason for the conflicting results in the literature is proposed. An approach to estimating tolerable upper intakes is also proposed. Research on in vivo sulfur amino acid metabolism in humans is tremendously difficult, and therefore, we do not wish to be overly critical of the high-quality work of the ambitious and highly intelligent men and women who have conducted various studies. Our goal is to objectively review the data for the reader in a logical and comprehensive manner and propose methods that may avoid difficulties in future studies.

Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids

“…Plasma concentrations of histidine, leucine, and tryptophan remained within the normal range, which suggests adequate supplementation of these AAs in the GMP diet (Table 6). Recent findings of a lower minimum requirement for methionine plus cysteine for school-age children (47) and adults (48) suggest that methionine supplementation is not required in GMP. In contrast, plasma concentration of tyrosine was below the normal range when measured in the fasting state (Table 6), which suggests that additional tyrosine supplementation may be required in GMP.…”

Intestinal metabolism of sulfur amino acids

“…The ability of cysteine to provide a proportion of the total sulfur amino acid requirements in man, hence providing a sparing effect on methionine requirement, has been extensively debated (12,21,23) . Many studies performed in animals have shown that more than 40 % of the sulfur amino acid requirement can be met by dietary cysteine (12,24 -28) .…”

Homocysteine and Polyamines: Metabolic Relationship and Its Clinical Significance in Folate Inhibitors Chemotherapy

“…ВЗАИМОСВЯЗЬ МЕЖДУ ОБМЕНОМ ПОЛИАМИНОВ, ФОЛАТНЫМ ОБМЕНОМ И ГОМОЦИСТЕИНОМ Исследования с использованием изотопов показали относительное восстановление коли-чества метионина в организме за счет обратно-го превращения гомоцистеина в метионин в ходе реметилирования [73,74]. Сложность измере-ния скорости реметилирования гомоцистеина заключается в том, что данная реакция может осуществляться двумя ферментативными путями: катализироваться повсеместно присутствующей метионинсинтетазой, использующей 5-метилтетра-гидрофолат в качестве метильного донора, а также фолатнезависимым путем с помощью бетаин-гомо-цистеин-метилтрансферазы (см.…”