PMID- 16156667
OWN - NLM
STAT- MEDLINE
DCOM- 20051114
LR  - 20131121
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 44
IP  - 37
DP  - 2005 Sep 20
TI  - The biosynthesis of heme O and heme A is not regulated by copper.
PG  - 12554-63
AB  - Heme A is an obligatory cofactor in all eukaryotic and many prokaryotic 
      cytochrome c oxidase (CcO) enzymes. Despite its obvious importance to CcO and the 
      electron transport pathway, essentially nothing is known concerning the 
      regulation of heme A. Because CcO is the only natural target for heme A and 
      copper is also required for CcO activity, it was postulated that copper might 
      regulate heme A homeostasis. Work reported previously demonstrated that there is 
      often a strong connection between copper and iron homeostasis in general, and 
      circumstantial evidence pointed to a possible specific link between copper and 
      heme A. To address this question, we conducted experiments to determine 
      rigorously whether copper plays a role in heme A homeostasis. The two enzymes 
      responsible for the conversion of heme B to heme A, heme O synthase (HOS) and 
      heme A synthase (HAS), were separately genomically epitope-tagged in 
      Saccharomyces cerevisiae, and their expression under various copper conditions 
      was quantified by Western blot analysis. These results demonstrated that the sum 
      of transcription, translation, and stability of HOS and HAS were independent of 
      copper. Additionally, the effects of intracellular copper concentrations on the 
      activity of HOS and HAS from Bacillus subtilis (expressed in Escherichia coli) 
      and Rhodobacter sphaeroides were examined by analysis of cellular heme extracts. 
      No trends with respect to intracellular copper were observed. In combination, our 
      results demonstrate that intracellular copper levels do not affect the 
      transcription, translation, stability, or activity of either HOS or HAS.
FAU - Morrison, M Scott
AU  - Morrison MS
AD  - Department of Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, 
      USA.
FAU - Cricco, Julia A
AU  - Cricco JA
FAU - Hegg, Eric L
AU  - Hegg EL
LA  - eng
GR  - GM66236/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Bacterial Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 137397-56-9 (heme O)
RN  - 18535-39-2 (heme a)
RN  - 42VZT0U6YR (Heme)
RN  - 789U1901C5 (Copper)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.- (CyoE protein, Bacteria)
SB  - IM
MH  - Alkyl and Aryl Transferases/metabolism
MH  - Bacillus subtilis/enzymology
MH  - Bacterial Proteins/metabolism
MH  - Copper/*pharmacology
MH  - Heme/*analogs & derivatives/biosynthesis
MH  - Homeostasis
MH  - Kinetics
MH  - Rhodobacter sphaeroides/enzymology
MH  - Saccharomyces cerevisiae/enzymology
MH  - Saccharomyces cerevisiae Proteins/metabolism
EDAT- 2005/09/15 09:00
MHDA- 2005/11/15 09:00
CRDT- 2005/09/15 09:00
PHST- 2005/09/15 09:00 [pubmed]
PHST- 2005/11/15 09:00 [medline]
PHST- 2005/09/15 09:00 [entrez]
AID - 10.1021/bi050893d [doi]
PST - ppublish
SO  - Biochemistry. 2005 Sep 20;44(37):12554-63. doi: 10.1021/bi050893d.