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Peroxisomes in Human Health and Disease: Metabolic Pathways, Metabolite Transport, Interplay with Other Organelles and Signal Transduction

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Peroxisomes and their Key Role in Cellular Signaling and Metabolism

Part of the book series: Subcellular Biochemistry ((SCBI,volume 69))

Abstract

Peroxisomes play a key role in human physiology as exemplified by the devastating consequences of a defect in peroxisome biogenesis as observed in patients affected by Zellweger syndrome. The main metabolic functions of peroxisomes in humans include: (1) fatty acid beta-oxidation; (2) etherphospholipid synthesis; (3) bile acid synthesis; (4) fatty acid alpha-oxidation, and (5) glyoxylate detoxification. Since peroxisomes lack a citric acid cycle and respiratory chain like mitochondria do, metabolism in peroxisomes requires continued cross-talk with other organelles, notably mitochondria and the endoplasmic reticulum in order to allow continued metabolism of the products generated by peroxisomes. Many of the metabolites which require peroxisomes for homeostasis, are involved in signal transduction pathways. These include the primary bile acids; platelet activating factor; plasmalogens, N-acylglycines and N-acyltaurines; docosahexaenoic acid as well as multiple prostanoids. The current state of knowledge in this area will be discussed in this review.

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Abbreviations

Acnat:

Acyl-CoA: amino acid N-acyltransferase

ACOX1:

Acyl-CoA oxidase 1

ACYL-DHAP:

Acyldihydroxyacetone phosphate

ADHAPS:

Alkyldihydroxyacetone phosphate synthase

AGT:

Alanine glyoxylate aminotransferase

ALD:

Adrenoleukodystrophy

BAAT:

Bile acid-CoA: amino acid N-acetyltransferase

BCOX:

Branched-chain acyl-CoA oxidase

BSEP:

Bile salt export pump

CA:

Cholic acid

CDCA:

Chenodeoxycholic acid

CPT1:

Carnitine palmityltransferase 1

CrAT:

Carnitine acetyltransferase

CrOT:

Carnitine octanoyltransferase

CYP7A1:

Cholesterol 7-Alpha-hydroxylase

DBP:

D-bifunctional protein

DHA:

Docosahexaenoic acid

DHCA:

Dihydroxycholestanoic acid

DHAPAT:

Dihydroxyacetone phosphate acyltransferase

EPL:

Etherphospholipid

ER:

Endoplasmic reticulum

FA:

Fatty acid

FGF:

Fibroblasts growth factor

FXR:

Farnesoid-X receptor

LBP:

L-bifunctional protein

LRH-1:

Liver receptor homologous Protein-1

LRM:

Lipid raft microdomains

LTE4:

Cysteinyl leukotriene-4

PAF:

Platelet activating factor

PD:

Peroxisomal disorder

ROS:

reactive oxygen species

SCPx:

Sterol-carrier-protein X

TH:

Thiolase

THCA:

Trihydroxycholestanoic acid

VLCFA:

Very long-chain fatty acids

ZS:

Zellweger syndrome

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Acknowledgement

The author gratefully acknowledges Mrs. Maddy Festen for expert preparation of the manuscript and Mr. Jos Ruiter for artwork.

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  1. Laboratory Genetic Metabolic Diseases, Room F0-226, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Ronald J. A. Wanders

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Correspondence to Ronald J. A. Wanders .

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  1. , Depto. Bioquímica, Biología Celular y, Estación Experimental del Zaidín, CSIC, Profesor Albareda 1, Granada, 18008, Spain

    Luis A. del Río

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Wanders, R.J.A. (2013). Peroxisomes in Human Health and Disease: Metabolic Pathways, Metabolite Transport, Interplay with Other Organelles and Signal Transduction. In: del Río, L. (eds) Peroxisomes and their Key Role in Cellular Signaling and Metabolism. Subcellular Biochemistry, vol 69. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6889-5_2

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