PMID- 29414770
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20230222
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 293
IP  - 15
DP  - 2018 Apr 13
TI  - Homocysteine regulates fatty acid and lipid metabolism in yeast.
PG  - 5544-5555
LID - 10.1074/jbc.M117.809236 [doi]
AB  - S-Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in 
      mammals) degrades AdoHcy, a by-product and strong product inhibitor of 
      S-adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine 
      and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy 
      levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, 
      with detrimental consequences for cellular methylation reactions. HHcy, a 
      pathological condition linked to cardiovascular and neurological disorders, as 
      well as fatty liver among others, is associated with a deregulation of lipid 
      metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that 
      dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated 
      cellular fatty acid and triacylglycerol content and induced a shift in fatty acid 
      composition, similar to changes observed in mutants lacking Sah1. Expression of 
      the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to 
      dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of 
      elevated Hcy. Expression of this pathway fully suppressed the growth deficit of 
      sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 
      mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the 
      deregulation of lipid metabolism in response to elevated Hcy in yeast. 
      Furthermore, Hcy supplementation in yeast led to increased resistance to 
      cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant 
      decline of condensing enzymes involved in very long-chain fatty acid synthesis, 
      in line with the observed shift in fatty acid content and composition.
CI  - (c) 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Visram, Myriam
AU  - Visram M
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
FAU - Radulovic, Maja
AU  - Radulovic M
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
FAU - Steiner, Sabine
AU  - Steiner S
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
FAU - Malanovic, Nermina
AU  - Malanovic N
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
FAU - Eichmann, Thomas O
AU  - Eichmann TO
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
FAU - Wolinski, Heimo
AU  - Wolinski H
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
FAU - Rechberger, Gerald N
AU  - Rechberger GN
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and.
AD  - the Omics Center Graz, BioTechMed-Graz, 8010 Graz, Austria.
FAU - Tehlivets, Oksana
AU  - Tehlivets O
AD  - From the Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 
      50, 8010 Graz, Austria and oksana.tehlivets@uni-graz.at.
LA  - eng
GR  - P 24216/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180206
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Fatty Acids)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 979-92-0 (S-Adenosylhomocysteine)
RN  - EC 3.3.1.1 (Adenosylhomocysteinase)
SB  - IM
MH  - Adenosylhomocysteinase/genetics/*metabolism
MH  - Fatty Acids/genetics/*metabolism
MH  - Hyperhomocysteinemia/genetics/metabolism
MH  - *Lipid Metabolism
MH  - Models, Biological
MH  - Mutation
MH  - S-Adenosylhomocysteine/*metabolism
MH  - Saccharomyces cerevisiae/genetics/*metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
PMC - PMC5900771
OTO - NOTNLM
OT  - S-adenosyl-L-homocysteine
OT  - S-adenosyl-L-homocysteine hydrolase
OT  - Saccharomyces cerevisiae
OT  - fatty acid
OT  - homocysteine
OT  - hyperhomocysteinemia
OT  - lipid
OT  - triacylglycerol
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2018/02/08 06:00
MHDA- 2018/12/18 06:00
PMCR- 2018/02/06
CRDT- 2018/02/08 06:00
PHST- 2017/07/31 00:00 [received]
PHST- 2018/02/05 00:00 [revised]
PHST- 2018/02/08 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/02/08 06:00 [entrez]
PHST- 2018/02/06 00:00 [pmc-release]
AID - S0021-9258(20)41851-4 [pii]
AID - M117.809236 [pii]
AID - 10.1074/jbc.M117.809236 [doi]
PST - ppublish
SO  - J Biol Chem. 2018 Apr 13;293(15):5544-5555. doi: 10.1074/jbc.M117.809236. Epub 
      2018 Feb 6.