About

Martha Stipanuk is associated with the Bronfenbrenner Center for Translational Research at Cornell University. The center assists faculty in developing translational research projects, providing support such as proposal preparation, training, technical support, and fostering collaborative relationships. The center also offers workshops, summer institutes, and talks on current research topics, aiming to facilitate the dissemination and funding of translational research. Specific details about her research focus, background, or key contributions are not provided in the available page text.

Research topics

• Chemistry
• Biochemistry
• Stereochemistry
• Internal medicine
• Medicine
• Endocrinology

Selected publications

• High Cysteine Diet Reduces Insulin Resistance in SHR-CRP Rats

  Physiological Research · 2021 · 5 citations

  • Internal medicine
  • Endocrinology
  • Chemistry

  Increased plasma total cysteine (tCys) has been associated with obesity and metabolic syndrome in human and some animal studies but the underlying mechanisms remain unclear. In this study, we aimed at evaluating the effects of high cysteine diet administered to SHR-CRP transgenic rats, a model of metabolic syndrome and inflammation. SHR-CRP rats were fed either standard (3.2 g cystine/kg diet) or high cysteine diet (HCD, enriched with additional 4 g L-cysteine/kg diet). After 4 weeks, urine, plasma and tissue samples were collected and parameters of metabolic syndrome, sulfur metabolites and hepatic gene expression were evaluated. Rats on HCD exhibited similar body weights and weights of fat depots, reduced levels of serum insulin, and reduced oxidative stress in the liver. The HCD did not change concentrations of tCys in tissues and body fluids while taurine in tissues and body fluids, and urinary sulfate were significantly increased. In contrast, betaine levels were significantly reduced possibly compensating for taurine elevation. In summary, increased Cys intake did not induce obesity while it ameliorated insulin resistance in the SHR-CRP rats, possibly due to beneficial effects of accumulating taurine.

  PublisherDOI

• Spectroscopic Investigation of Cysteamine Dioxygenase

  Biochemistry · 2020 · 24 citations

  • Chemistry
  • Biochemistry
  • Stereochemistry

  -dependent thiol dioxygenases. This finding suggests that the secondary coordination sphere of ADO is distinct from those of CDO and MDO, demonstrating the significant role that secondary-sphere residues play in dictating substrate specificity.

  PublisherOA PDFDOI

• Metabolism of Sulfur-Containing Amino Acids: How the Body Copes with Excess Methionine, Cysteine, and Sulfide

  Journal of Nutrition · 2020 · 145 citations

  1st authorCorresponding
  • Chemistry
  • Biochemistry
  PublisherOA PDFDOI

• Effects of single amino acid deficiency on mRNA translation are markedly different for methionine versus leucine

  Scientific Reports · 2018-05-18 · 65 citations

  articleOpen accessSenior author

  Although amino acids are known regulators of translation, the unique contributions of specific amino acids are not well understood. We compared effects of culturing HEK293T cells in medium lacking either leucine, methionine, histidine, or arginine on eIF2 and 4EBP1 phosphorylation and measures of mRNA translation. Methionine starvation caused the most drastic decrease in translation as assessed by polysome formation, ribosome profiling, and a measure of protein synthesis (puromycin-labeled polypeptides) but had no significant effect on eIF2 phosphorylation, 4EBP1 hyperphosphorylation or 4EBP1 binding to eIF4E. Leucine starvation suppressed polysome formation and was the only tested condition that caused a significant decrease in 4EBP1 phosphorylation or increase in 4EBP1 binding to eIF4E, but effects of leucine starvation were not replicated by overexpressing nonphosphorylatable 4EBP1. This suggests the binding of 4EBP1 to eIF4E may not by itself explain the suppression of mRNA translation under conditions of leucine starvation. Ribosome profiling suggested that leucine deprivation may primarily inhibit ribosome loading, whereas methionine deprivation may primarily impair start site recognition. These data underscore our lack of a full understanding of how mRNA translation is regulated and point to a unique regulatory role of methionine status on translation initiation that is not dependent upon eIF2 phosphorylation.

  PublisherOA PDFDOI

• Cysteine dioxygenase is essential for mouse sperm osmoadaptation and male fertility

  FEBS Journal · 2018-03-31 · 25 citations

  articleOpen access

  Sperm entering the epididymis are immotile and cannot respond to stimuli that will enable them to fertilize. The epididymis is a highly complex organ, with multiple histological zones and cell types that together change the composition and functional abilities of sperm through poorly understood mechanisms. Sperm take up taurine during epididymal transit, which may play antioxidant or osmoregulatory roles. Cysteine dioxygenase (CDO) is a critical enzyme for taurine synthesis. A previous study reported that male CDO −/− mice exhibit idiopathic infertility, prompting us to investigate the functions of CDO in male fertility. Immunoblotting and quantitative reverse transcription‐polymerase chain reaction analysis of epididymal segments showed that androgen‐dependent CDO expression was highest in the caput epididymidis. CDO −/− mouse sperm demonstrated a severe lack of in vitro fertilization ability. Acrosome exocytosis and tyrosine phosphorylation profiles in response to stimuli were normal, suggesting normal functioning of pathways associated with capacitation. CDO −/− sperm had a slight increase in head abnormalities. Taurine and hypotaurine concentrations in CDO −/− sperm decreased in the epididymal intraluminal fluid and sperm cytosol. We found no evidence of antioxidant protection against lipid peroxidation. However, CDO −/− sperm exhibited severe defects in volume regulation, swelling in response to the relatively hypo‐osmotic conditions found in the female reproductive tract. Our findings suggest that epididymal CDO plays a key role in post‐testicular sperm maturation, enabling sperm to osmoregulate as they transition from the male to the female reproductive tract, and provide new understanding of the compartmentalized functions of the epididymis.

  PublisherOA PDFDOI

• Identification of Taurine-Responsive Genes in Murine Liver Using the Cdo1-Null Mouse Model

  Advances in experimental medicine and biology · 2017-01-01 · 7 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice

  Annals of the New York Academy of Sciences · 2016-01-01 · 18 citations

  articleSenior authorCorresponding

  To gain further insights into the effects of elevated cysteine levels on energy metabolism and the possible mechanisms underlying these effects, we conducted studies in cysteine dioxygenase (Cdo1)-null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression are also seen in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggests impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2 S production and impairments in energy metabolism suggest that H2 S signaling could be involved.

  PublisherDOI

• Structure-Based Insights into the Role of the Cys–Tyr Crosslink and Inhibitor Recognition by Mammalian Cysteine Dioxygenase

  Journal of Molecular Biology · 2016-07-30 · 37 citations

  articleCorresponding
  PublisherDOI

• GCN2- and eIF2α-phosphorylation-independent, but ATF4-dependent, induction of CARE-containing genes in methionine-deficient cells

  Amino Acids · 2016-09-10 · 41 citations

  articleSenior author
  PublisherDOI

• Mammalian Cysteine Dioxygenase

  Encyclopedia of Inorganic and Bioinorganic Chemistry · 2015-09-14 · 4 citations

  other

  Abstract Cysteine dioxygenase (CDO) is a mononuclear nonheme Fe(II) enzyme that catalyzes the oxidation of l ‐cysteine to l ‐cysteinesulfinic acid (CSA) by addition of both atoms of molecular oxygen to the cysteine sulfur. Mammalian CDO is highly expressed in the liver, the pancreas, the adipose tissue, the kidney and the lungs, and the CSA produced is further converted to either taurine or sulfate plus pyruvate. To maintain cysteine levels within the narrow range required for health, mammalian CDO is regulated by the modulation of enzyme turnover and through formation of a Cys93‐Tyr157 crosslink that increases its activity over 10‐fold. Imbalances in cysteine metabolism have been observed in several neurological disorders, and CDO has been identified as a tumor suppressor. Bacterial CDOs also exist, as do a variety of related thiol dioxygenases that have been less well studied. High‐resolution crystal structures of CDO reveal iron coordination by three histidines. Cysteine coordinates the iron by its amino and thiolate groups, leaving a sixth coordination site open for dioxygen. A cysteine persulfenate has been trapped in the active site, but despite substantial spectroscopic studies and theoretical calculations, the details of the mechanism are still a matter of debate and it is uncertain if this is an intermediate.

  PublisherDOI

Recent grants

• NIH Grant R01DK026959

  NIH · $321k · 1989

• NIH Grant R01AM026959

  NIH · $92k · 1986

• NIH Grant R01DK064303

  NIH · $636k · 2008

• NIH Grant R56DK083473

  NIH · $193k · 2010

• Nutritional Regulation of Cysteine Dioxygenase

  NIH · $4.0M · 2000–2015

Frequent coauthors

• Lawrence L. Hirschberger

  Cornell University

  47 shared

• John E. Dominy

  20 shared

• Heather B. Roman

  Cornell University

  15 shared

• C.R. Simmons

  Arizona State University

  12 shared

• Relicardo M. Coloso

  University of San Agustin

  11 shared

• Iori Ueki

  Cornell University

  9 shared

• James De La Rosa

  Duke University Hospital

  9 shared

• Halina Jurkowska

  Jagiellonian University

  9 shared

Education

• B.S.

  University of Kentucky

• M.S.

  Cornell University

• Ph.D., nutritional biochemistry

  University of Wisconsin-Madison

Awards & honors

• Fellow of the American Society for Nutrition (2015)
• Emerita status (2018)