Skip to Main Content
  • Become an Access Reviewer
  • Clinical Phenotypes
  • OMMBID Advisory banner
  • Ommbid banner
  • Ommbid latest banner

Abstract

Abstract 

  1. Peroxisomes are single-membrane lined organelles present in virtually all eukaryotic cells. In most human cells, their abundance ranges from less than a hundred to more than a thousand peroxisomes per cell. The granular matrix of the organelle contains more than 50 matrix enzymes that participate in a wide variety of metabolic pathways including β-oxidation of certain fatty acids and biosynthesis of ether phospholipids, bile acids, and isoprene compounds.

  2. Peroxisome biogenesis involves synthesis of the matrix proteins on free cytosolic ribosomes followed by receptor-mediated import into the organelle. Most matrix proteins are targeted by a C-terminal peroxisome targeting sequence (PTS1) with a consensus of −S-K-L-COOH that is recognized by a cytosolic receptor, PEX5. A few matrix proteins are targeted by an N-terminal PTS2 with the consensus sequence of −R-L-XS-H-L−. Peroxisome membrane proteins are specific for the organelle. They are also synthesized on free cytosolic ribosomes and are targeted to the organelle by mechanism(s) that are separate from and less well understood than those used by matrix proteins.

  3. PEX genes encode peroxins, proteins involved in and necessary for peroxisome biogenesis. These include the PTS1 and 2 receptors, as well as additional cytosolic and integral membrane proteins that are involved in the import of peroxisomal matrix and membrane proteins. To date, 23 PEX genes have been identified, with 15 PEX genes known in humans.

  4. The peroxisome biogenesis disorders are comprised of at least 12 complementation groups. Defective biogenesis of the organelle leads to complex developmental and metabolic phenotypes that can be organized into two clinical spectra: the Zellweger spectrum with Zellweger syndrome as the most severe example and neonatal adrenoleukodystrophy and infantile Refsum disease as milder variants. The second spectrum is distinctive with classical rhizomelic chondrodysplasia punctata as its exemplar and milder variants described.

  5. The PEX genes responsible for 11 of the 12 PBD complementation groups are known with multiple mutant alleles identified. Functional analysis of the proteins encoded by these PEX genes together with careful clinical, metabolic, and cellular characterization of the mutant phenotypes has provided insight into the pathophysiology of the peroxisome biogenesis disorders as well as into the normal biology of peroxisome assembly and function.

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.

Ok

About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

OMMBID Full Site: One-Year Subscription

Connect to the full suite of OMMBID content including new and revised chapters that reflect the latest research, image galleries, clinical phenotypes, and more.

$295 USD
Buy Now

Pay Per View: Timed Access to all of OMMBID

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.