Decaprenyl pyrophosphate synthetase from mitochondria of pig liver

doi:10.1016/0006-291X(83)90551-X

Biochemical and Biophysical Research Communications

Volume 116, Issue 2, 31 October 1983, Pages 500-506

https://doi.org/10.1016/0006-291X(83)90551-X Get rights and content

Abstract

Decaprenyl pyrophosphate synthetase which catalyzes the synthesis of all- $trans$ -decaprenyl pyrophosphate from isopentenyl pyrophosphate and either farnesyl pyrophosphate or geranylgeranyl pyrophosphate has been partially purified from mitochondria of pig liver. This enzyme lacks dimethylallyl-transferring and geranyl-transferring activities.

References (16)

J.K. Dorsey et al.
J. Biol. Chem
(1966)
T.K. Wong et al.
J. Biol. Chem
(1982)
K. Momose et al.
J. Biol. Chem
(1972)
G.R. Daleo et al.
FEBS Lett
(1977)
H. Fujii et al.
J. Biol. Chem
(1982)
D.F. Parsons et al.
Methods Enzymol
(1967)
I. Takahashi et al.
J. Biol. Chem
(1980)
P.W. Holloway et al.
Biochem. J
(1967)

There are more references available in the full text version of this article.

Cited by (19)

Isotopic labelings for mechanistic studies
2024, Methods in Enzymology
The intricate mechanisms in the biosynthesis of terpenes belong to the most challenging problems in natural product chemistry. Methods to address these problems include the structure-based site-directed mutagenesis of terpene synthases, computational approaches, and isotopic labeling experiments. The latter approach has a long tradition in biosynthesis studies and has recently experienced a revival, after genome sequencing enabled rapid access to biosynthetic genes and enzymes. Today, this allows for a combined approach in which isotopically labeled substrates can be incubated with recombinant terpene synthases. These clearly defined reaction setups can give detailed mechanistic insights into the reactions catalyzed by terpene synthases, and recent developments have substantially deepened our understanding of terpene biosynthesis. This chapter will discuss the state of the art and introduce some of the most important methods that make use of isotopic labelings in mechanistic studies on terpene synthases.
Targeting the Mevalonate Pathway in Cancer
2021, Trends in Cancer
Citation Excerpt :
There are also studies of the addition of isopentenyl pyrophosphate to tRNA, a process known as isopentenylation, and its role in cancer [28]. While these studies may result in niche applications of statins, they do not explain the more widely reported dependency on GGPP, as ubiquinone and dolichol can be derived from FPP [60–63] (Figure 1). GGPP is utilized for the conversion of vitamin K1 to vitamin K2 [64] by UBIAD1, an enzyme that also directs HMGCR degradation [65,66].
The mevalonate synthesis inhibitors, statins, are mainstay therapeutics for cholesterol management and cardiovascular health. Thirty years of research have uncovered supportive roles for the mevalonate pathway in numerous cellular processes that support oncogenesis, most recently macropinocytosis. Central to the diverse mechanisms of statin sensitivity is an acquired dependence on one mevalonate pathway output, protein geranylgeranylation. New chemical prenylation probes and the discovery of a novel geranylgeranyl transferase hold promise to deepen our understanding of statin mechanisms of action. Further, insights into statin selection and the counterproductive role of dietary geranylgeraniol highlight how we should assess statins in the clinic. Lastly, rational combination strategies preview how statins will enter the oncology toolbox.
Incorporation of all-trans-farnesol into sterols and ubiquinone in Nicotiana tabacum L. cv Bright Yellow-2 cell cultures
2001, Tetrahedron Letters
Isoprenyl diphosphate synthases
2000, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Isoprenyl diphosphate synthases catalyze consecutive condensations of isopentenyl diphosphates with allylic primer substrates to form linear backbones for all isoprenoid compounds including cholesterol. These synthases are classified according to the final chain length of their end products and the stereochemistry of the newly formed double bonds. Mutagenesis and X-ray crystallography data have uncovered the basic catalytic and chain length determination mechanisms of E-isoprenyl diphosphate synthases and shed light on their possible evolutionary course. Although much less is known about the Z-isoprenyl diphosphate synthase family, successful cloning and subsequent crystallizations in the near future will no doubt bring more insight as researchers begin to unravel the essential components and precise reaction mechanisms of this cellular machinery.
A pathway where polyprenyl diphosphate elongates in prenyltransferase: Insight into a common mechanism of chain length determination of prenyltransferases
1998, Journal of Biological Chemistry
Prenyltransferases catalyze the consecutive condensations of isopentenyl diphosphate to produce linear polyprenyl diphosphates. Each enzyme forms the final product with a specific chain length. The product specificity of an enzyme is thought to be determined by the structure around the unknown path through which the product elongates in the enzyme. To explore the path, we introduced a few mutations at the 5th, the 8th, and/or the 11th positions before the first aspartate-rich motif of geranylgeranyl-diphosphate synthase or farnesyl-diphosphate synthase. The side chains of these amino acids are situated on the same side of an α-helix. In geranylgeranyl-diphosphate synthase, a single mutated enzyme (F77S) mainly produces a C₂₅ product (Ohnuma, S.-I., Hirooka, K., Hemmi, H., Ishida, C., Ohto, C., and Nishino, T. (1996)J. Biol. Chem. 271, 18831–18837). A double mutated enzyme (L74G and F77G) mainly produces a C₃₅ compound with significant amounts of C₃₀ and C₄₀. A triple mutated enzyme (I71G, L74G, and F77G) mainly produces a C₄₀compound with C₃₅ and C₄₅. Mutated farnesyl-diphosphate synthases also show similar patterns. These findings indicate that the elongating product passages on a surface of the side chains of the mutated amino acids, the original bulky amino acids had blocked the elongation, and the path is conserved in prenyltransferases. Moreover, the fact that some double and triple mutated enzymes can also form small amounts of products longer than C₅₀ indicates that the paths in these mutated enzymes can partially access the outer surface of the enzymes.
Possible involvement of 3-hydroxymethylglutaryl-CoA reductase in determining the side-chain length of ubiquinone in rat heart
1991, Archives of Biochemistry and Biophysics
The biosynthetic mechanism for determining the side-chain length of ubiquinone in rat heart mitochondria was investigated. The biosynthesis of nonaprenyl ubiquinone (UQ-9) and decaprenyl ubiquinone (UQ-10) in the mitochondria from rat hearts previously perfused with mevalonolactone was accelerated depending on the concentration of mevalonolactone. Furthermore the synthesis ratio between UQ-10 and UQ-9 (UQ-10/UQ-9) increased in accordance with the increasing concentration of mevalonolactone used. In addition, an enhancement of the synthesis ratio (UQ-10/UQ-9) was observed when the rats were treated with isoproterenol to increase the activity of 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme which forms mevalonate. Moreover, the addition of isopentenyl pyrophosphate, which is a metabolite of mevalonate, elevated the synthetic ratios UQ-10/UQ-9 in intact mitochondria and decaprenyl pyrophosphate/solanesyl pyrophosphate in the partially purified polyprenyl pyrophosphate synthetase from rat heart. These results suggest that the HMG-CoA reductase could be involved as a determining factor of the side-chain length of ubiquinone in rat heart.

View all citing articles on Scopus

View full text

Decaprenyl pyrophosphate synthetase from mitochondria of pig liver

Abstract

J. Biol. Chem

J. Biol. Chem

J. Biol. Chem

FEBS Lett

J. Biol. Chem

Methods Enzymol

J. Biol. Chem

Biochem. J