A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast
(2007) In The FEBS Journal 274(7). p.1804-1817- Abstract
- In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal... (More)
- In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V-max/K-m = 0.78 U.mg(-1).mM(-1)), but can also use GABA (V-max/K-m = 0.42 U.mg(-1).mM(-1)), while SkUga1p only uses GABA (V-max/K-m = 4.01 U.mg(-1).mM(-1)). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/670462
- author
- Andersen, Gorm LU ; Andersen, Birgit LU ; Dobritzsch, Doreen ; Schnackerz, Klaus D. and Piskur, Jure LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- gene duplication, gamma-aminobutyrate, aminotransferase, beta-alanine, Saccharomyces kluyveri
- in
- The FEBS Journal
- volume
- 274
- issue
- 7
- pages
- 1804 - 1817
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000244883400017
- scopus:33947244361
- ISSN
- 1742-464X
- DOI
- 10.1111/j.1742-4658.2007.05729.x
- language
- English
- LU publication?
- yes
- id
- 0be02a97-07f7-490c-94c9-a7abb77a7502 (old id 670462)
- date added to LUP
- 2016-04-01 17:01:19
- date last changed
- 2022-03-15 04:38:18
@article{0be02a97-07f7-490c-94c9-a7abb77a7502, abstract = {{In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiae UGA1 and Schizosaccharomyces pombe UGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V-max/K-m = 0.78 U.mg(-1).mM(-1)), but can also use GABA (V-max/K-m = 0.42 U.mg(-1).mM(-1)), while SkUga1p only uses GABA (V-max/K-m = 4.01 U.mg(-1).mM(-1)). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity.}}, author = {{Andersen, Gorm and Andersen, Birgit and Dobritzsch, Doreen and Schnackerz, Klaus D. and Piskur, Jure}}, issn = {{1742-464X}}, keywords = {{gene duplication; gamma-aminobutyrate; aminotransferase; beta-alanine; Saccharomyces kluyveri}}, language = {{eng}}, number = {{7}}, pages = {{1804--1817}}, publisher = {{Wiley-Blackwell}}, series = {{The FEBS Journal}}, title = {{A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast}}, url = {{http://dx.doi.org/10.1111/j.1742-4658.2007.05729.x}}, doi = {{10.1111/j.1742-4658.2007.05729.x}}, volume = {{274}}, year = {{2007}}, }