Absence of Cystathionase in Human Fetal Liver: Is Cystine Essential?

Sturman, John A.; Gaull, Gerald E.; Räihä, Niels C. R.

doi:10.1126/science.169.3940.74

Cited by 324 publications

(148 citation statements)

References 13 publications

(3 reference statements)

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“…fetus seems to be totally dependent on maternal transfer of cysteine because of absent cystathionase activity both in the fetus and placenta (14,15). Unlike other amino acids, the concentration of cysteine is lower in the fetal than the maternal circulation (28).…”

Section: Discussionmentioning

confidence: 99%

“…The fact that cystathionase activity is absent from the fetus (14) and that all three transsulfuration enzymes are absent from the placenta (1 5), suggests that the fetus is entirely dependent on the mother for its supply of cysteine. Inasmuch as cystathionase does not become active until some time after birth, the newborn, especially the newborn premature infant, is dependent on a dietary source of cysteine for at least the first few weeks of life, in order to ensure an adequate intake (16).…”

mentioning

confidence: 99%

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Hepatic Metallothionein as a Source of Zinc and Cysteine during the First Year of Life

Zlotkin

Cherian

1988

Pediatr Res

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ABSTRACT. Metallothionein, a high cysteine-containing protein, can bind with both essential and nonessential metals and thus play an important role as a metal storage protein and also in the detoxification of toxic metals. Although in the human fetus, levels of trace minerals and metallothionein are very high, their postnatal changes are not well documented. The purpose of the present investigation, therefore, was to quantify the accumulation of metallothionein in premature and full-term infants during the first year of life and to identify factors affecting its accumulation. From 47 postmortem samples, it was determined that hepatic metallothionein levels were highest in newborn premature and full-term infants falling to levels found in older children by 4.4 months of age. Hepatic zinc levels were also highest in the youngest infants, falling with increasing postnatal age. There was a significant positive correlation between zinc and metallothionein at all ages. However, there was a negative correlation between hepatic metallothionein levels and cystathionase activity. Hepatic copper and metallothionein levels were unrelated. The renal concentration of metallothionein, zinc, and copper were significantly lower than corresponding hepatic levels. The fall in hepatic levels of zinc and metallothionein during the first months of life correspond to a period of negative zinc balance and low endogenous cysteine production in the newborn. Thus metallothionein may play an important role as a storage depot for these two essential nutrients during this critical period of active growth. (Pediatr Res 24: 326-329, 1988) During the last trimester of pregnancy the mature placenta regulates the transfer of nutrients and protects the fetus from potentially toxic substances. With premature birth, the newborn infant is at risk of both nutrient deficiencies and toxicities for at least five reasons. I) Nutrient intake requirements may be unknown thus too much or too little may be provided; 2) homeostatic mechanisms in the functionally immature preterm are poorly developed; 3) the immature blood-brain bamer is more permeable to any elements present in the plasma; 4) growth is extremely rapid, thus nutrient needs are highest at the same time that nutrient stores are very low; and 5) postnatal adaptation may be prolonged for months even in the absence of overt disease. This combination of factors demand that both environmental and nutritional factors be rigidly controlled for the newborn premature infant.It has been established that most of the minerals of the human fetus are layed down during the last trimester of pregnancy (1).

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hepatic Metallothionein as a Source of Zinc and Cysteine during the First Year of Life

Zlotkin

Cherian

1988

Pediatr Res

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“…Females reach term with anencephaly three times more often than males, see (Elwood and Elwood, 1980). The human embryo/fetus has both less efficient transsulfuration and remethylation abilities when compared to the adult (Sturman, et al, 1970, Skovby, 1989 (Fig. 3).…”

Section: And 2)mentioning

confidence: 99%

A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton

Björklund¹,

Gordon²

2006

Int. J. Dev. Biol.

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Neural tube defects are serious congenital malformations which can be prevented by periconceptional folic acid supplementation. We hypothesize that folic acid provides the methyl group used for post-translational methylation of arginine and histidine in the highly conserved regulatory domains of the cytoskeleton and that these are required for neural tissue differentiation. Presumptive neural tissue has an unusually high need for folates due to the activity of phosphoethanolamine methyl transferase in producing neural tissue specific lipids at a time when the cytoskeleton is also competing for methylation. According to the cell state splitter hypothesis, the cytoskeleton is required to coordinate the spatial and temporal component of differentiation. When folate supply is low and the cytoskeleton is not methylated properly, the result is a neural tube defect due to failure of this coordination.

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“…The CSE/cysteine deficiency appeared to be pathogenic because treatment with cysteine or its precursor N-acetylcysteine was beneficial (8). Cysteine is a semiessential amino acid with multifaceted cellular functions (14,15). Cysteine is obtained from both, the diet and by endogenous production via the reverse transsulfuration pathway (16,17).…”

mentioning

confidence: 99%

Transcriptional control of amino acid homeostasis is disrupted in Huntington’s disease

Sbodio

Snyder

Paul

2016

Proc. Natl. Acad. Sci. U.S.A.

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Disturbances in amino acid metabolism, which have been observed in Huntington’s disease (HD), may account for the profound inanition of HD patients. HD is triggered by an expansion of polyglutamine repeats in the protein huntingtin (Htt), impacting diverse cellular processes, ranging from transcriptional regulation to cognitive and motor functions. We show here that the master regulator of amino acid homeostasis, activating transcription factor 4 (ATF4), is dysfunctional in HD because of oxidative stress contributed by aberrant cysteine biosynthesis and transport. Consistent with these observations, antioxidant supplementation reverses the disordered ATF4 response to nutrient stress. Our findings establish a molecular link between amino acid disposition and oxidative stress leading to cytotoxicity. This signaling cascade may be relevant to other diseases involving redox imbalance and deficits in amino acid metabolism.

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Absence of Cystathionase in Human Fetal Liver: Is Cystine Essential?

Cited by 324 publications

References 13 publications

Hepatic Metallothionein as a Source of Zinc and Cysteine during the First Year of Life

Hepatic Metallothionein as a Source of Zinc and Cysteine during the First Year of Life

A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton

Transcriptional control of amino acid homeostasis is disrupted in Huntington’s disease

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