The ontogeny of the glucose-6-phosphatase enzyme in human embryonic and fetal red blood cells

Hume, Robert; Pazouki, Sima; Hallas, Anne; Burchell, Ann

doi:10.1016/0378-3782(95)01626-e

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…Prior to this study, the earliest that UGT enzymes had been reported in development was the presence of UGT immunoreactive cells in human liver parenchyme 32 days postovulation and in nucleated embryonic red blood cells 47 days postovulation (Hume et al, 1996). Such early expression caused speculation that UGTs may play a role in human embryogenesis.…”

Section: Discussionmentioning

confidence: 95%

UDP-Glucuronosyltransferase 1a Enzymes Are Present and Active in the Mouse Blastocyst

et al. 2014

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The UDP-glucuronosyltransferase (UGT) enzymes are critical for regulating nutrients, hormones, and endobiotics, as well as for detoxifying xenobiotics. Human and murine fetuses are known to express glucuronidation enzymes, but there are currently no data prior to implantation. Here we addressed this gap in knowledge and tested whether Ugt enzymes are already present in preimplantation-stage embryos. Blastocysts were obtained after in vitro fertilization with gametes from B6D2F1 hybrid mice and from embryo culture. Protein expression and localization were determined using pan-specific UGT1A and UGT2B, as well as anti-human isoform-specific antibodies. Immunofluorescence analysis showed that blastocysts expressed Ugt1a globally, in the cytoplasm and nuclei of all of the cells. Western blots demonstrated the presence of Ugt1a6 but not Ugt1a1, Ugt1a3, Ugt1a4, or Ugt1a9. The Ugt2b proteins were not detected by either assay. The level of Ugt activity in murine blastocysts was comparable with that of the adult human liver (per milligram of protein), but the activity of β-glucuronidase, an Ugt-partnering enzyme responsible for substrate regeneration, was lower. Altogether, these data confirm that Ugt1a proteins are present and active in preimplantation murine embryos and point to a potential role for these proteins in implantation and early embryonic and fetal development.

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Section: Discussionmentioning

confidence: 95%

UDP-Glucuronosyltransferase 1a Enzymes Are Present and Active in the Mouse Blastocyst

et al. 2014

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“…Hemoglobin (Hb) has a variety of functions in vertebrates including oxygen transport, CO 2 transport, acid-base balance (Brittain, 2002), nitric oxide transport (Allen and Piantadosi, 2006), oxygen storage and buffering (Baumann and Dragon, 2005) as well as a number of indirect functions arising from the metabolic machinery associated with the red blood cell in which the hemoglobin resides (Hume et al, 1996). Of these functions, blood O 2 transport generally is consider the most critical (Burggren, 2004).…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin enhances oxygen uptake in larval zebrafish (Danio rerio) but only under conditions of extreme hypoxia

Rombough

Drader

2009

Journal of Experimental Biology

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SUMMARYThe role of hemoglobin (Hb) in O 2 uptake by zebrafish larvae ranging in age from 5 to 42 days postfertilization was assessed under conditions of normoxia, moderate hypoxia and extreme hypoxia. This was achieved by exposing larvae with and without functional Hb to continuously declining oxygen levels (P O2 ) in closed-system respirometers. Exposure to 5% CO for 2-4 h was used to render Hb effectively non-functional in terms of its ability to transport O 2 . Routine metabolic rate (rM O2 ), critical dissolved oxygen level (P c ) and residual oxygen level (P r ) were determined and used, respectively, as indicators of response in normoxia, moderate hypoxia and extreme hypoxia. rM O2 was defined as the average rate of O 2 uptake before O 2 became limiting (i.e. at high P O2 s). P c is the P O2 at which rM O2 first becomes O 2 -limited and P r is the P O2 below which larvae are no longer able to extract O 2 from the ambient medium. CO poisoning had no significant impact on rM O2 or P c at any age, indicating that the lack of functional Hb does not impair routine O 2 usage in normoxia or at moderate levels of hypoxia [down to at least 25-50 torr (1 torrϷ0.133 kPa), depending on age]. P r , however, was significantly lower overall for control larvae (6.7±1.1 torr; mean ± 95%CI) than for COpoisoned larvae (11.2±2.1 torr). It would appear that the presence of functional Hb allows zebrafish larvae to extract O 2 from water down to lower P O2 s under conditions of extreme hypoxia. This is the first documented (as opposed to inferred) benefit of Hb in developing zebrafish. However, given the relatively small magnitude of the effect it is unclear if this benefit on its own is sufficient to balance the costs associated with Hb production and maintenance.

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“…While this is not always true, the UGT enzymes are an example of a critical drug elimination pathway that does not mature until after birth [36][37][38][39][121][122][123][124][125][126]. Although UGTs can be detected as early as the blastocyst stage in mammalian development (indicating a possible role in embryology) [127] in fetal red blood cells and in the fetal liver [128][129][130], glucuronidation activity has not been detected until 30 --40 weeks of gestation [122,123]. This is not due to a lack of UDPGA co-substrate, because the human fetal liver and kidney as well as the placenta contain UDPGA at the same concentrations as adults [131].…”

Section: Ontogenetic Regulation Of Ugtmentioning

confidence: 99%

Posttranscriptional regulation of uridine diphosphate glucuronosyltransferases

Riches¹,

Collier²

2015

Expert Opinion on Drug Metabolism & Toxicology

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Posttranscriptional regulation of UGTs has traditionally received less attention than nuclear regulation, in part because mechanisms involving ribosomes and endoplasmic reticula are challenging to investigate. Most promising of the posttranscriptional mechanisms reviewed are likely to be effects on co-substrate (UDP-glucuronic acid) transport and availability and structure-function changes to UGT proteins through, for example, glycosylation and phosphorylation. Although classical biochemistry continues to illuminate many aspects of UGT function, advances in proteomics and structural biology are beginning to assist in the determination of posttranscriptional regulation mechanisms for UGTs.

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The ontogeny of the glucose-6-phosphatase enzyme in human embryonic and fetal red blood cells

Cited by 12 publications

References 29 publications

UDP-Glucuronosyltransferase 1a Enzymes Are Present and Active in the Mouse Blastocyst

UDP-Glucuronosyltransferase 1a Enzymes Are Present and Active in the Mouse Blastocyst

Hemoglobin enhances oxygen uptake in larval zebrafish (Danio rerio) but only under conditions of extreme hypoxia

Posttranscriptional regulation of uridine diphosphate glucuronosyltransferases

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