The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: Human Tyrosine Aminotransferase (TAT, P17735)

1. Gene and Protein Identity

The human TAT gene (Ensembl: ENSG00000198650) encodes tyrosine aminotransferase (UniProt: P17735; EC 2.6.1.5), also known as L-tyrosine:2-oxoglutarate aminotransferase. The gene is located on chromosome 16q22.1–q22.5, contains 12 exons, and encodes a 454-amino acid protein (alsharhan2020disordersofphenylalanine pages 28-29, OpenTargets Search: tyrosinemia-TAT). It is important to note that the gene symbol "TAT" is shared with the HIV-1 transactivator of transcription protein (Tat); this report exclusively addresses the human hepatic tyrosine aminotransferase enzyme.

The following table summarizes the key molecular and functional properties of human TAT:

Table: This table summarizes the core molecular, biochemical, cellular, and disease-related properties of human tyrosine aminotransferase (TAT, UniProt P17735). It is useful as a compact reference for functional annotation and report writing.

2. Enzymatic Function and Catalytic Mechanism

2.1 Primary Reaction

Human TAT catalyzes the reversible transamination of L-tyrosine to 4-hydroxyphenylpyruvate (4-HPP, also referred to as p-hydroxyphenylpyruvate or pHPP), using α-ketoglutarate (2-oxoglutarate) as the amino group acceptor, with the concomitant production of L-glutamate (xu2020generalandspecialized pages 2-5, scherman2020drugrepositioningfor pages 3-5). This reaction represents the first and rate-limiting step in the tyrosine catabolic pathway (alsharhan2020disordersofphenylalanine pages 28-29, holme2013tyrosinemetabolism pages 1-2). The overall reaction can be written as:

L-tyrosine + 2-oxoglutarate ⇌ 4-hydroxyphenylpyruvate + L-glutamate

2.2 Cofactor and Mechanism

TAT belongs to the class-I pyridoxal-5′-phosphate (PLP)-dependent aminotransferase family (parthasarathy2018athreeringcircus pages 4-5, xu2020generalandspecialized pages 2-5, alsharhan2020disordersofphenylalanine pages 28-29). Like other PLP-dependent aminotransferases, TAT operates via a ping-pong bi-bi mechanism. In the first half-reaction, the PLP cofactor forms an internal aldimine (Schiff base) with a catalytic lysine residue. The amino acid substrate displaces the lysine to form an external aldimine, and following a 1,3-prototropic shift, a ketimine intermediate is formed. Hydrolysis of this intermediate releases the α-keto acid product and leaves the cofactor in the pyridoxamine-5′-phosphate (PMP) form. In the second half-reaction, the amino group is transferred from PMP to the acceptor α-keto acid (α-ketoglutarate), regenerating PLP and releasing glutamate. Structural studies on related family I aminotransferases reveal that upon substrate binding, the smaller domain of the homodimer moves toward the larger domain, closing the active site pocket to properly position substrates for catalysis (parthasarathy2018athreeringcircus pages 4-5).

2.3 Substrate Specificity and Side Activities

While L-tyrosine is the canonical physiological substrate, TAT also efficiently transamines L-phenylalanine (parthasarathy2018athreeringcircus pages 4-5, parthasarathy2018athreeringcircus pages 2-4). A systematic investigation of human cytosolic transaminase side activities by Caligiore et al. (2022) demonstrated that TAT, along with five other human cytosolic transaminases (GOT1, GPT, GTK, PSAT1, BCAT1), was tested against amino acids whose primary degradation pathways do not typically involve transamination. TAT exhibited notable side activity toward L-tryptophan, displaying relatively high apparent k_cat and high apparent K_M values for L-Trp transamination, suggesting it could contribute to a minor pathway for L-Trp degradation (caligiore2022humancytosolictransaminases pages 6-8, caligiore2022humancytosolictransaminases pages 5-6). In contrast, reactions with L-Thr, L-Arg, L-Lys, and L-Asn were consistently very slow across all tested transaminases (caligiore2022humancytosolictransaminases pages 5-6). For recombinant expression studies, the first 40 codons of the human TAT coding sequence were removed to obtain a shortened recombinant protein compatible with soluble expression (caligiore2022humancytosolictransaminases pages 2-4).

3. Subcellular Localization and Tissue Expression

3.1 Subcellular Localization

Human TAT functions predominantly as a cytosolic enzyme (alsharhan2020disordersofphenylalanine pages 28-29, caligiore2022humancytosolictransaminases pages 2-4). The designation of TAT as "cytosolic tyrosine aminotransferase" distinguishes it from the mitochondrial aspartate aminotransferase isoform. Donini et al. (2009) confirmed that the TAT gene encodes the cytosolic tyrosine aminotransferase in humans (caligiore2022humancytosolictransaminases pages 2-4). Although one source mentions possible transport to mitochondria (alsharhan2020disordersofphenylalanine pages 28-29), the predominant body of evidence identifies the cytosol as the primary functional compartment.

3.2 Tissue Expression

TAT is synthesized almost exclusively in hepatic parenchymal cells of the liver (jantzen1987cooperativityofglucocorticoid pages 1-2). Tyrosine degradation occurs primarily in the liver, with minor degradation activity detected in the kidney (holme2013tyrosinemetabolism pages 1-2). Expression of TAT increases rapidly after birth in a developmentally regulated manner, and glucocorticoid hormones and cAMP can prematurely activate TAT gene expression, suggesting a role for these signaling molecules in developmental control of tyrosine catabolism (jantzen1987cooperativityofglucocorticoid pages 1-2).

4. Biochemical Pathway: Tyrosine Catabolism

TAT catalyzes the first step of the five-enzyme tyrosine degradation pathway, which converts L-tyrosine to the tricarboxylic acid (TCA) cycle intermediates fumarate and the ketone body acetoacetate. The complete pathway and its associated inborn errors of metabolism are presented below:

Table: This table summarizes the complete five-step human tyrosine catabolic pathway from tyrosine to fumarate and acetoacetate. It also links each enzymatic step to the inherited disorder caused by deficiency of that enzyme, making it useful for functional annotation and clinical interpretation.

The pathway begins with TAT-catalyzed transamination of tyrosine to 4-hydroxyphenylpyruvate. This intermediate is then oxidized by 4-hydroxyphenylpyruvate dioxygenase (HPD) to homogentisic acid (scherman2020drugrepositioningfor pages 3-5, holme2013tyrosinemetabolism pages 2-4). Homogentisate 1,2-dioxygenase (HGD) cleaves the aromatic ring to produce maleylacetoacetate, which is isomerized by maleylacetoacetate isomerase (GSTZ1) to fumarylacetoacetate. Finally, fumarylacetoacetate hydrolase (FAH) cleaves fumarylacetoacetate into fumarate and acetoacetate, completing the catabolic sequence (scherman2020drugrepositioningfor pages 3-5, holme2013tyrosinemetabolism pages 1-2). This pathway connects aromatic amino acid catabolism to central carbon metabolism and energy production. Perturbations at each step result in distinct inherited metabolic diseases, as detailed in the table above.

Beyond this primary catabolic route, alternative biotransformation products arise from the major pathway metabolites. Norman et al. (2022) identified 13 phase 1 and phase 2 biotransformation products from phenylalanine through to homogentisic acid, representing alternative clearance routes that minimize hypertyrosinemia, particularly when the pathway is pharmacologically inhibited by nitisinone (norman2022comprehensivebiotransformationanalysis pages 1-2).

5. Transcriptional Regulation

The TAT gene is one of the best-characterized models for hormonal gene regulation. TAT expression is potently induced by glucocorticoids at the transcriptional level. Jantzen et al. (1987) identified two glucocorticoid response elements (GREs) located approximately 2.5 kb upstream of the transcription initiation site that cooperatively mediate hormonal induction. The proximal GRE alone lacks inherent transcriptional stimulatory capacity but synergistically enhances glucocorticoid induction when combined with the distal GRE, resulting in approximately 15-fold increases in TAT mRNA expression upon dexamethasone treatment (jantzen1987cooperativityofglucocorticoid pages 1-2, jantzen1987cooperativityofglucocorticoid pages 2-3). In addition to glucocorticoids, cAMP also directly activates TAT gene transcription (jantzen1987cooperativityofglucocorticoid pages 1-2).

Chromatin remodeling plays a critical role in TAT gene regulation. Upon glucocorticoid treatment, the GR recruits FOXA1/2 transcription factors to the glucocorticoid response unit (GRU), followed by stable recruitment of C/EBP factors. After 2–3 days of dexamethasone treatment, CpG dinucleotides within the GRU are demethylated, providing a form of transcriptional "gene memory" for subsequent glucocorticoid stimulation (chang2026hepaticglucocorticoidreceptor pages 7-7). Insulin can counteract glucocorticoid-induced TAT transcription through mechanisms involving the glucocorticoid receptor's ligand-binding domain (chang2026hepaticglucocorticoidreceptor pages 19-19).

6. Structural and Evolutionary Context

6.1 Protein Structure

Human TAT is a homodimeric enzyme, consistent with other members of the class I aminotransferase superfamily (parthasarathy2018athreeringcircus pages 4-5, jensen1996evolutionaryrecruitmentof pages 2-3). Each subunit contains the PLP cofactor covalently bound to a conserved lysine residue via a Schiff base linkage. The enzyme contains domains characteristic of the aminotransferase I/II superfamily, including the large aminotransferase domain (IPR004839), the pyridoxal-phosphate binding site motif (IPR004838), and the smaller substrate-binding domain (IPR015422). Structural studies on related aminotransferases show that substrate binding triggers a conformational change in which the smaller domain moves toward the larger domain to close the active-site pocket, properly positioning the substrate for catalysis (parthasarathy2018athreeringcircus pages 4-5).

6.2 Evolutionary Classification

TAT belongs to the broader Family I of PLP-dependent aminotransferases, which share a common protein scaffold and catalytic mechanism (jensen1996evolutionaryrecruitmentof pages 4-7, jensen1996evolutionaryrecruitmentof pages 7-8). However, mammalian cytosolic TAT is evolutionarily distinct from bacterial TyrB enzymes. While bacterial TyrB (e.g., from E. coli) is classified in subfamily Ia alongside aspartate aminotransferases, rat cytosolic TAT clusters within subfamily Ig, and Jensen and Gu (1996) suggested it may warrant its own subfamily status due to distinctly different substrate specificities compared to other subfamily Ig members such as kynurenine aminotransferase and glutamine transaminase K (jensen1996evolutionaryrecruitmentof pages 3-4). A homolog of mammalian TAT was identified in Trypanosoma cruzi with 39% sequence identity, though the parasitic version demonstrates broader substrate specificity, accepting all three aromatic amino acids and multiple amino group acceptors (jensen1996evolutionaryrecruitmentof pages 3-4).

The evolution of aromatic amino acid specificity within Family I aminotransferases involved multiple structural modifications rather than simple point mutations. Site-directed mutagenesis studies converting E. coli AspC to TyrB substrate specificity required six simultaneous residue changes, indicating that evolutionary recruitment of aromatic substrate binding involved coordinated rearrangements of the active-site pocket (jensen1996evolutionaryrecruitmentof pages 8-10). The active-site pocket of aromatic aminotransferases is larger and more hydrophobic compared to aspartate-specific enzymes, with a key leucine at position 39 creating hydrophobic interactions critical for aromatic substrate accommodation (jensen1996evolutionaryrecruitmentof pages 8-10).

7. Clinical Significance: Tyrosinemia Type II

Loss-of-function mutations in the TAT gene cause tyrosinemia type II (OMIM #276600), also known as Richner-Hanhart syndrome or oculocutaneous tyrosinemia (alsharhan2020disordersofphenylalanine pages 28-29, OpenTargets Search: tyrosinemia-TAT). This autosomal recessive disorder is characterized by the classic triad of bilateral dendritic (pseudodendritic) keratitis, painful palmoplantar hyperkeratotic lesions, and occasionally mild intellectual disability (alsharhan2020disordersofphenylalanine pages 28-29). The pathogenesis of the ocular and skin manifestations is attributed to an inflammatory response secondary to tyrosine crystal deposition in tissues, resulting from markedly elevated plasma tyrosine levels (alsharhan2020disordersofphenylalanine pages 28-29).

The Open Targets Platform assigns a high disease-target association score of 0.793 between TAT and tyrosinemia type II, with a definitive classification from the ClinGen Aminoacidopathy Gene Curation Expert Panel confirming TAT as the causative gene (OpenTargets Search: tyrosinemia-TAT). No clear genotype-phenotype correlation has been identified among the various reported TAT mutations (alsharhan2020disordersofphenylalanine pages 28-29).

Treatment consists of a low-protein diet supplemented with a medical formula free of phenylalanine and tyrosine, aiming to reduce plasma tyrosine levels below 500 μmol/L (alsharhan2020disordersofphenylalanine pages 31-33). This dietary intervention results in resolution of eye and skin symptoms within days to several weeks. Early dietary management in infancy, maintaining serum tyrosine concentrations between 300–800 μmol/L, is associated with normal psychomotor development (alsharhan2020disordersofphenylalanine pages 31-33). Recent reviews emphasize that newborn screening programs have enabled early detection and reduced morbidity from this and related disorders of tyrosine metabolism (alsharhan2020disordersofphenylalanine pages 31-33).

8. Recent Developments

Recent research on TAT has focused on several areas. Caligiore et al. (2022) provided the most detailed characterization to date of human cytosolic TAT side activities, demonstrating that the enzyme can transaminate L-tryptophan with appreciable efficiency, expanding our understanding of its potential physiological roles beyond tyrosine catabolism (caligiore2022humancytosolictransaminases pages 6-8, caligiore2022humancytosolictransaminases pages 5-6). Norman et al. (2022) identified alternative biotransformation routes in phenylalanine-tyrosine metabolism using comprehensive metabolomic approaches, revealing 13 phase 1 and phase 2 biotransformation products that serve as alternative clearance mechanisms when the canonical pathway is disrupted (norman2022comprehensivebiotransformationanalysis pages 1-2). Shakerdi et al. (2025) reviewed the current therapeutic landscape for inborn errors of amino acid metabolism including TAT deficiency, noting that while dietary management remains the cornerstone of treatment, novel approaches including gene therapy are under preclinical investigation for related disorders. Barretta et al. (2025) highlighted the importance of differential diagnosis between tyrosinemia type II (TAT deficiency) and maleylacetoacetate isomerase deficiency (GSTZ1 mutations), as both can present with elevated succinylacetone on newborn screening.

9. Summary

Human tyrosine aminotransferase (TAT) is a cytosolic, PLP-dependent homodimeric enzyme that catalyzes the first and rate-limiting step of tyrosine catabolism in the liver, converting L-tyrosine and α-ketoglutarate to 4-hydroxyphenylpyruvate and L-glutamate. It belongs to the class I aminotransferase superfamily (subfamily Ig) and functions primarily in hepatic parenchymal cells. Its expression is tightly regulated by glucocorticoids, cAMP, and insulin, and is developmentally activated at birth. Loss-of-function mutations cause tyrosinemia type II (Richner-Hanhart syndrome), an autosomal recessive disorder characterized by oculocutaneous manifestations due to tyrosine crystal deposition. Beyond its canonical tyrosine substrate, TAT also accepts phenylalanine and demonstrates side activity toward L-tryptophan, pointing to a broader metabolic versatility than previously appreciated.

References

1. (alsharhan2020disordersofphenylalanine pages 28-29): Hind Alsharhan and Can Ficicioglu. Disorders of phenylalanine and tyrosine metabolism. Translational Science of Rare Diseases, 5:3-58, Jul 2020. URL: https://doi.org/10.3233/trd-200049, doi:10.3233/trd-200049. This article has 41 citations.

2. (OpenTargets Search: tyrosinemia-TAT): Open Targets Query (tyrosinemia-TAT, 8 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

3. (parthasarathy2018athreeringcircus pages 4-5): Anutthaman Parthasarathy, Penelope J. Cross, Renwick C. J. Dobson, Lily E. Adams, Michael A. Savka, and André O. Hudson. A three-ring circus: metabolism of the three proteogenic aromatic amino acids and their role in the health of plants and animals. Frontiers in Molecular Biosciences, Apr 2018. URL: https://doi.org/10.3389/fmolb.2018.00029, doi:10.3389/fmolb.2018.00029. This article has 435 citations.

4. (xu2020generalandspecialized pages 2-5): Jing-Jing Xu, Xin Fang, Chen-Yi Li, Lei Yang, and Xiao-Ya Chen. General and specialized tyrosine metabolism pathways in plants. aBIOTECH, 1:97-105, Sep 2020. URL: https://doi.org/10.1007/s42994-019-00006-w, doi:10.1007/s42994-019-00006-w. This article has 127 citations.

5. (jensen1996evolutionaryrecruitmentof pages 2-3): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.

6. (caligiore2022humancytosolictransaminases pages 2-4): Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, and Alessio Peracchi. Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates. Cellular and Molecular Life Sciences: CMLS, Jul 2022. URL: https://doi.org/10.1007/s00018-022-04439-3, doi:10.1007/s00018-022-04439-3. This article has 19 citations.

7. (holme2013tyrosinemetabolism pages 1-2): Elisabeth Holme and Grant A. Mitchell. Tyrosine Metabolism, pages 23-31. Springer Berlin Heidelberg, Jan 2013. URL: https://doi.org/10.1007/978-3-642-40337-8_2, doi:10.1007/978-3-642-40337-8_2. This article has 18 citations.

8. (jantzen1987cooperativityofglucocorticoid pages 1-2): Hans-Michael Jantzen, Uwe Strähle, Bernd Gloss, Francis Stewart, Wolfgang Schmid, Michael Boshart, Richard Miksicek, and Günther Schütz. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell, 49:29-38, Apr 1987. URL: https://doi.org/10.1016/0092-8674(87)90752-5, doi:10.1016/0092-8674(87)90752-5. This article has 855 citations and is from a highest quality peer-reviewed journal.

9. (scherman2020drugrepositioningfor pages 3-5): Daniel Scherman and Christine Fetro. Drug repositioning for rare diseases: knowledge-based success stories. Therapies, 75:161-167, Apr 2020. URL: https://doi.org/10.1016/j.therap.2020.02.007, doi:10.1016/j.therap.2020.02.007. This article has 74 citations.

10. (caligiore2022humancytosolictransaminases pages 6-8): Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, and Alessio Peracchi. Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates. Cellular and Molecular Life Sciences: CMLS, Jul 2022. URL: https://doi.org/10.1007/s00018-022-04439-3, doi:10.1007/s00018-022-04439-3. This article has 19 citations.

11. (alsharhan2020disordersofphenylalanine pages 31-33): Hind Alsharhan and Can Ficicioglu. Disorders of phenylalanine and tyrosine metabolism. Translational Science of Rare Diseases, 5:3-58, Jul 2020. URL: https://doi.org/10.3233/trd-200049, doi:10.3233/trd-200049. This article has 41 citations.

12. (jensen1996evolutionaryrecruitmentof pages 4-7): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.

13. (jensen1996evolutionaryrecruitmentof pages 3-4): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.

14. (parthasarathy2018athreeringcircus pages 2-4): Anutthaman Parthasarathy, Penelope J. Cross, Renwick C. J. Dobson, Lily E. Adams, Michael A. Savka, and André O. Hudson. A three-ring circus: metabolism of the three proteogenic aromatic amino acids and their role in the health of plants and animals. Frontiers in Molecular Biosciences, Apr 2018. URL: https://doi.org/10.3389/fmolb.2018.00029, doi:10.3389/fmolb.2018.00029. This article has 435 citations.

15. (caligiore2022humancytosolictransaminases pages 5-6): Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, and Alessio Peracchi. Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates. Cellular and Molecular Life Sciences: CMLS, Jul 2022. URL: https://doi.org/10.1007/s00018-022-04439-3, doi:10.1007/s00018-022-04439-3. This article has 19 citations.

16. (holme2013tyrosinemetabolism pages 2-4): Elisabeth Holme and Grant A. Mitchell. Tyrosine Metabolism, pages 23-31. Springer Berlin Heidelberg, Jan 2013. URL: https://doi.org/10.1007/978-3-642-40337-8_2, doi:10.1007/978-3-642-40337-8_2. This article has 18 citations.

17. (norman2022comprehensivebiotransformationanalysis pages 1-2): Brendan P. Norman, Andrew S. Davison, Bryony Hickton, Gordon A. Ross, Anna M. Milan, Andrew T. Hughes, Peter J. M. Wilson, Hazel Sutherland, Juliette H. Hughes, Norman B. Roberts, George Bou-Gharios, James A. Gallagher, and Lakshminarayan R. Ranganath. Comprehensive biotransformation analysis of phenylalanine-tyrosine metabolism reveals alternative routes of metabolite clearance in nitisinone-treated alkaptonuria. Metabolites, 12:927, Sep 2022. URL: https://doi.org/10.3390/metabo12100927, doi:10.3390/metabo12100927. This article has 11 citations.

18. (jantzen1987cooperativityofglucocorticoid pages 2-3): Hans-Michael Jantzen, Uwe Strähle, Bernd Gloss, Francis Stewart, Wolfgang Schmid, Michael Boshart, Richard Miksicek, and Günther Schütz. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell, 49:29-38, Apr 1987. URL: https://doi.org/10.1016/0092-8674(87)90752-5, doi:10.1016/0092-8674(87)90752-5. This article has 855 citations and is from a highest quality peer-reviewed journal.

19. (chang2026hepaticglucocorticoidreceptor pages 7-7): Maggie Chang and Jen-Chywan Wang. Hepatic glucocorticoid receptor action and glucose homeostasis. Endocrine Reviews, 47:52-74, Sep 2026. URL: https://doi.org/10.1210/endrev/bnaf030, doi:10.1210/endrev/bnaf030. This article has 7 citations and is from a domain leading peer-reviewed journal.

20. (chang2026hepaticglucocorticoidreceptor pages 19-19): Maggie Chang and Jen-Chywan Wang. Hepatic glucocorticoid receptor action and glucose homeostasis. Endocrine Reviews, 47:52-74, Sep 2026. URL: https://doi.org/10.1210/endrev/bnaf030, doi:10.1210/endrev/bnaf030. This article has 7 citations and is from a domain leading peer-reviewed journal.

21. (jensen1996evolutionaryrecruitmentof pages 7-8): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.

22. (jensen1996evolutionaryrecruitmentof pages 8-10): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.

Artifacts

• Edison artifact artifact-00
• Edison artifact artifact-01

Citations

1. alsharhan2020disordersofphenylalanine pages 28-29
2. parthasarathy2018athreeringcircus pages 4-5
3. caligiore2022humancytosolictransaminases pages 5-6
4. caligiore2022humancytosolictransaminases pages 2-4
5. jantzen1987cooperativityofglucocorticoid pages 1-2
6. holme2013tyrosinemetabolism pages 1-2
7. scherman2020drugrepositioningfor pages 3-5
8. norman2022comprehensivebiotransformationanalysis pages 1-2
9. chang2026hepaticglucocorticoidreceptor pages 7-7
10. chang2026hepaticglucocorticoidreceptor pages 19-19
11. jensen1996evolutionaryrecruitmentof pages 3-4
12. jensen1996evolutionaryrecruitmentof pages 8-10
13. alsharhan2020disordersofphenylalanine pages 31-33
14. xu2020generalandspecialized pages 2-5
15. jensen1996evolutionaryrecruitmentof pages 2-3
16. caligiore2022humancytosolictransaminases pages 6-8
17. jensen1996evolutionaryrecruitmentof pages 4-7
18. parthasarathy2018athreeringcircus pages 2-4
19. holme2013tyrosinemetabolism pages 2-4
20. jantzen1987cooperativityofglucocorticoid pages 2-3
21. jensen1996evolutionaryrecruitmentof pages 7-8
22. https://doi.org/10.3233/trd-200049,
23. https://doi.org/10.3389/fmolb.2018.00029,
24. https://doi.org/10.1007/s42994-019-00006-w,
25. https://doi.org/10.1128/jb.178.8.2161-2171.1996,
26. https://doi.org/10.1007/s00018-022-04439-3,
27. https://doi.org/10.1007/978-3-642-40337-8_2,
28. https://doi.org/10.1016/0092-8674(87
29. https://doi.org/10.1016/j.therap.2020.02.007,
30. https://doi.org/10.3390/metabo12100927,
31. https://doi.org/10.1210/endrev/bnaf030,