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FUNCTIONAL CATEGORY DESCRIPTION
ABC transporters Transporters that include the ATP Binding Cassette (ABC). All known peroxisomes have at least one ABC transporter, therefore are highly conserved throughout the evolution. For example, in mammals, there are 4 peroxisomal ABC transporters: ABCD1, ABCD2, ABCD3 and ABCD4. Lack of function of ABCD1, or Ald, causes a severe human disease: the X-linked Adrenoleukodystrophy.
Alpha-oxidation This function is present in vertebrates and in Caenorhabditis elegans is predicted. The alpha-oxidation removes the terminal carboxyl group as CO2 displacing the 3-methyl, in 3-methyl-branched fatty acids, to a position that allows the following beta-oxidation steps. One of the most important 3-methyl branched fatty acid is phytanic acid. Enzymes involved in the alpha-oxidation:

a) FACL1 or LACS: activates phytanic acid to phytanoyl-CoA,

b) PHYH: hydroxylates the phytanoyl CoA,

c) HPCL2: decarboxylates to pristanal,

d) pristanalDH: dehydrogenates pristanal to pristanic,

e) VLACS: activates pristanic to prystanoyl-CoA,

f) IDH1: produces oxoglutarate used by PhyH.

Antiinflammatory-antimicrobial Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. The gene encoding the nitric oxide synthase is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. It has been identified in peroxisomes of rats and humans.
Antioxidant Peroxisome plays a key ROLE in the detoxification of the harmful hydrogen peroxide. Beside this ROLE, peroxisome spread as well this function to the detoxification of more ROS: superoxide, epoxides and alkyl-hydroperoxides.
Biosynthesis of cysteine and sulfur assimilation The cystathionine -lyase Str3 is a peroxisomal S. cerevisiae enzyme involved in amino acid metabolism, in this case in the transulfuration pathway from cysteine to homocysteine. Gto1 acts as a glutaredoxin that would regulate the redox state of target cysteine residues through its deglutathionylating activity.
Branched chain fatty acid beta-oxidation Branched chain fatty acids have a carbon scaffold with methyl branches. The enzymes that allow the properly beta-oxidation are:

a) ACOX2 (it belongs to the acyl-CoA oxidases family and carries on the first dehydrogenation),

ACOX3 (it belongs to the acyl-CoA oxidases family and is involved in branched chain FA oxidation only in rodentia. It carries on the first dehydrogenation),

c) HSD17B4 (D-PBE) (hydration and dehydrogenation again, rely on the bifunctional protein),

d) SCPX (Sterol carrier protein X carries on the thyolitic cleavage).
Branched chain fatty acid oxidation Branched chain fatty acids have a carbon scaffold with methyl branches. In mammals, the enzymes that allow the oxidation are:

a) enzymes that allow the alpha-oxidation, displacing the 3-methyl from the fatty acid scaffold,

b) AMACR, which converts (2R)-methyl fatty acids to (2S)-methyl fatty acids,

c) and the beta-oxidation enzymes.
Carbohydrate Metabolism
Catalase Catalase allows the degradation of the harmful hydrogen peroxide, produced in the peroxisome by several hydrogen-peroxide-producing oxidases, yielding water and oxygen.
D-amino acid degradation In the peroxisome there are two peroxide-producing oxidases (DAO and DDO) that carry out the degradation of D-amino acids. The more suitable substrates for DAO are D-proline and glycine, whereas for DDO are D-aspartate and NMDA.
Di- trihydroxycholestanoic acid beta-oxidation Oxidation of di- and trihydroxycholestanoic acid, which are intermediates in the formation of the primary bile acids, performed by the enzymes of the beta-oxidation pathway.
Di- trihydroxycholestanoic acid oxidation/Bile acid synthesis Oxidation of di- and trihydroxycholestanoic acid, which are intermediates in the formation of the primary bile acids. Is included the AMACR enzyme, which catalyses an essential reaction of isomerisation, and the beta-oxidation steps.
Epoxide/Isochorismatase hydrolases Epoxide hydrolases convert epoxides to dihydrodioles.
Etherlipid and plasmalogens synthesis Ether-phospholipids or plasmalogens are a special class of phospholipids characterized by a vinyl ether bond at the sn-1 position of the glycerol backbone. This pathway is widespread in peroxisomal bearing organisms except in plants and fungus. In mammals, usually at sn-1 the fatty acid sterified is a C16:0 (palmitic acid), C18:0 (stearic acid) or C18:1 (oleic acid), at sn-2 is a polyunsaturated fatty acids, such as arachidonic (AA) or docosahexaenoic (DHA) acids, and at sn-3 there is an ethanolamine or choline. The first two steps of the synthesis of plasmalogens are exclusively peroxisomal, and the following steps might occur in peroxisomes and endoplasmatic reticulum.
Fatty acid chain elongation Peroxisome is focused on fatty acid oxidation, but presence of the trans 2-enoyl-CoA reductase (PECR) in chordata suggests that could also play a ROLE in fatty acid synthesis. This enzyme may catalyse the irreversible ACOX reaction. As long as the beta-oxidation is reversible except for ACOX reaction, the presence of PECR could allow complete the reverse beta-oxidation and, therefore, the chain elongation.
Fatty acid oxidation Peroxisome plays a key ROLE in the oxidation of fatty acids (FA) in all peroxisomal bearing organisms. The peroxisome FA substrates in mammals are mainly:

1) 1) very-long-chain fatty acids like C26:0, which are oxidized by the straight chain FA pathway

2) methyl-branched FA like phytanic acid, which are oxidized by the branched chain FA pathway

3) intermediates of the primary bile acids, which are oxidized by the di- and trihydroxycolestanoic acid oxidation pathway

4) and dicarboxylics acids oxidized by the long-chain dicarboxylics pathway.
Fatty acid synthesis/PUFAS synthesis Peroxisomal beta-oxidation can produce polyunsaturated fatty acids (PUFAs) by shortening the carbon-chain, instead of elongating as it happens in the endoplasmatic reticulum. The PUFAs synthetized in the peroxisome are docosahexaenoic acid (DHA, C22:6n-3), the main compound in plasmalogens, and docosapentaenoic acid (C22:5n-3). We included the only enzyme involved in chain elongation (PECR).
Gluthatione peroxidase/Thioredoxin Glutathione S-transferase kappa (hGSTK1) has been detected in the peroxisome, suggesting a new function for this family of enzymes.
Glycerol metabolism Only two enzymes are ascribed to this category. The glycosomal Glycerol kinase (GK) of trypanosomatids and the glycerol-3-phosphate dehydrogenase (GPD1) in yeasts. During anaerobiosis Saccharomyces cerevisiae strongly increases glycerol production by GPD1 to provide for non-respiratory oxidation of NADH to NAD(+).
Glycolysis and biosynthesis of sugar nucleotides Kinetoplastidia peroxisomes, called glycosomes, cointain most of the glycolytic enzymes.
Glycosyl hydrolases
Glyoxylate and dicarboxylate metabolism Glyoxylate cycle allows the synthesis of macromolecules from dicarboxylates compounds such as ethanol and acetate. Metazoans in general, including humans, use glucose as the main carbon source and lack this cycle. Yeasts, plants and trypanosomatids have this cycle. In humans,the glyoxylate is a toxic metabolite wich undergoes oxalate formation. The oxalate precipitates as calcium oxalate with severe consequences for the tissues involved. Under normal conditions oxalate is converted to glycine by glyoxylate aminotransferase (AGT).
Isoprenoid metabolism
Jasmonic metabolism
L-Lysine metabolism L-lysine can be degradated by two distinct routes: the saccharophine and the L-pipecolate pathways. Up to day, only the enzyme L-pipecolate oxidase (PIPOX) has been related to the L-Lysine degradation in the peroxisome, via the L-pipecolate pathway.
Lipid metabolism Peroxisome metabolism is focused on lipid metabolism, in mammals primarily on oxidation of very long fatty acids (FA), methyl-branched FA, intermediates of the primary bile acids and dicarboxylic acids, as well as on synthesis of plasmalogens and synthesis of polyunsaturated FA (PUFAs). Its contribution in the isoprenoid/cholesterol pathway is controversial. Malonyl-CoA decarboxylase (MLYCD) has been suggested to be involved in fatty acid synthesis and oxidation.
Long-chain dicarboxylic acids oxidation Dicarboxylic acids are omega-oxidation products of monocarboxylic acids. In mammals, the monocarboxylic acid is omega-hydroxylated by a microsomal P450, then is alcohol and aldehyde dehydrogenated in the cytosol and, finally, is shortened in the peroxisome by the peroxisomal beta-oxidation.
Long/very long fatty acids activation The long-chain fatty acid Coenzyme-A ligases activate the fatty acid by an esterification reaction with a Coenzyme-A. This allows the acyl-CoA to cross the membrane by specific transporters.
Metabolism Peroxisomal metabolism is focused on lipid oxidation and hydrogen peroxide detoxification and, in less extension, on amino acid and purine oxidation.
Nicotinate and nicotinamide metabolism NAD is an ubiquitous molecule that participates in many metabolic reactions. It also plays important ROLEs in transcriptional regulation, longevity, calorie-restriction-mediated life-span extension and age-associated diseases. In yeast, it has been shown that NAD affects longevity and transcriptional silencing. NAD is synthesised via two major pathways in both prokaryotic and eukaryotic systems: the de novo pathway and the salvage pathway.
Pentose-phosphate pathway
Peroxiredoxin Peroxiredoxins may play an antioxidant protective ROLE against oxidative stress products, such as hydrogen peroxide and alkyl hydroperoxides. In the peroxisome have been identified PRDX1, PRDX5, and 2-Cysteine peroxiredoxins family with Tryparedoxin peroxidase activity.
Peroxisomal AAA-ATPases Peroxins that belong to the ATPase family. They are associated with various cellular activities (AAA), often acting as chaperone-like proteins. PEX1 and PEX6 share similarities with membrane-fusion ATPases, suggesting a ROLE in membrane formation. Otherwise, a ROLE in disassembly of protein complexes and PEX5 recycling can be proposed.
Peroxisomal membrane proteins (PMP) Peroxisomal membrane proteins that are not peroxins. Included are:

a) the peroxisomal ABC transporters,

b) the PXMP4 family, with unknown function,

c) the PXMP2 family, which integrates proteins carrying the Mpv17 domain, and

d) the PXMP34 family, that belongs to the solute carrier protein family.
Peroxisome biogenesis (peroxins) Essential peroxisomal proteins involved in the biogenesis of the peroxisome. Their loss of function abrogates the organelle formation, causing severe human diseases: Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease or rhizomelic chondrodysplasia punctata type 1.
Peroxisome division-proliferation Peroxins that play a ROLE in the division or proliferation of the organelle. Yeast are the eukaryotes with more proteins relying on this function. PEX11 is commonly present, except in the unicellular diatom T. pseudonana.
Peroxisome docking The Peroxins PEX13 and PEX14 interact with the soluble receptors Pex5 and PEX7 and with the peroxisome surface, allowing the docking of the peroxisomal target proteins to the peroxisome.
Peroxisome matrix protein import Peroxins that allow the import of proteins targeted to the peroxisomal matrix. Peroxins relying on target signal recognition, protein docking and protein translocation, should be considered playing a ROLE in this function too.
Peroxisome membrane assembly Peroxins that allow the organelle membrane assembly. Yeast are the eukaryotes with more proteins relying on this function. PEX3 and PEX19 (peroxisomal markers), and PEX16, are highly conserved throughout the evolution.
Peroxisome organization Non-peroxin proteins involved in the peroxisome biogenesis and organization, can perform an essential but transient ROLE in peroxisome division.
Peroxisome targeting sequence binding Peroxins that recognize the peroxisomal target signals PTS1 (i.e. PEX5) and PTS2 (i.e. PEX7 and PEX20), in order to import the proteins to the organelle. Both PEX5 and PEX7 are widespread except for some exceptions like C. elegans, which lacks PEX7.
Photorespiration
Polyamines degradation Polyamines are required for numerous important processes such as wound healing, tissue growth and diferentitaion, and tumor growth. The peroxisomal enzyme PAO plays a ROLE in regulation of intracellular polyamine concentration, acting as a determinant of cellular sensitivity to the antitumor polyamine analogs. N(1)-acetylated polyamines and, in less extension, spermine, are substrates for PAO.
Proteases Only two proteases has been detected in peroxisome: the recently identified lon protease LONP, and the insulin-degrading enzyme IDE. The presence of IDE suggests a peroxisomal ROLE in the carbohydrate metabolism.
Protein kinases
Protein/amino acid metabolism Peroxisome plays a ROLE in the amino acid metabolism, focusing on amino acid oxidation such as D-amino acids, L-lysine, transaminases and polyamine degradation. Beside this ROLE, we have also included the two peroxisomal proteases LONP and IDE.
Purines and pyrimidines In trypanosomatids have been identified glycosomal enzymes of the purine salvage pathway and the de novo pyrimidine biosynthetic pathway. In addition, in some metazoa have been identified two enzymes involved in purine metabolism in peroxisome: xanthine oxidase (XDH) and urate oxidase (UOX). XDH exist in two functionally forms, the dehydrogenase and the oxidase. The last form induces cell damage by producing reactive oxygen metabolites, and lack of its function undergoes xanthinuria. UOX catalyses the oxidation of urate, yielding hydrogen peroxides. Multiple mutations of the urate oxidase have resulted in loss of that enzyme in humans and primates.
PXMP 2/4 family proteins Proteins that belong to the PXMP2 family ( proteins having the MPV17 domain) and the PXMP4 family (only one protein). The PXMP2 family proteins may play a ROLE in the ROS metabolism.
PXMP 34 family proteins Only the membrane protein PXMP34 is present in this group. PXMP34 belongs to the solute carrier protein family, but its function in the peroxisome is not well known. However, the orthologue protein in S. cerevisiae, YPR128cp, most likely mediates the transport of ATP across the peroxisomal membrane.
Regulation of acyl-CoA/CoA ratio Enzymes that regulates the Coenzyme A pool, which may also affect the acyl-CoAs pool, abrogate the chain-shortening completion during the FA-oxidation, or avoid the oxidation. The enzymes considered are:

a) carnitine acetyltransferases CRAT and COT,

b) acyl-CoA thioesterases PTE1, PTE2, PTE2a and PTE2b

c)Coenzyme A diphosphatases (NUDIXs) that hydrolyse the Coenzyme A.
Retinoid metabolism Only one peroxisomal enzyme, a retinal reductase, has been related to the retinoid metabolism. In mammals, this enzyme reduces retinal in the absence or presence of the retinoid specific binding protein CRBP(I) into retinol. Its function may prevent high and potentially toxic steady-state concentrations of retinal.
Straight chain fatty acids beta-oxidation Enzymes of the beta-oxidation pathway implicated in the oxidation of straight chain fatty acids, such as very long fatty acids C26 and C24. Straight fatty acids have a carbon scaffold without methyl-branches. These enzymes are ACOX1, D-PBE, ACAA1 and SCPX and are widespread in the peroxisomal bearing organisms.
Straight chain fatty acids oxidation Enzymes involved in the oxidation of straight chain fatty acids. Here are included:

a) the ABC transporter that allows the fatty acid transport across the peroxisomal membrane,

b) enzymes carrying out the beta-oxidation pathway ACOX1, D-PBE, ACAA1 and SCPX,

c) CROT, which transfers the carnitine to an acyl not completely oxidized,

d) the thioesterases PTE1, PTE2, PTE2a and PTE2b, that regulates the acyl-CoA esterification and control the fatty acid shorting during the beta-oxidation.
Superoxide dismutase Superoxide dismutases convert harmful superoxide radicals to molecular oxygen and hydrogen peroxide. SOD1 (Cu/ZnSOD) and SOD2 (MnSOD) have been detected in peroxisomes of mammals.
Transaminases Enzymes that carry out the transfer of an amino group to an acceptor, usually a 2-oxo acid.
Unknown This group includes the proteins with currently unknown function.
Unsaturated fatty acid beta-oxidation The beta-oxidation of unsaturated fatty acids needs additional steps, in order to displace the double bonds to proper positions allowing beta-oxidation. Beta-oxidation of unsaturated fatty acid with double bounds extending from even-numbered carbons yields 2,4-dienoyl-CoAs. When the double bounds are extending from odd-numbered carbons, 2,5-dienoyl-CoAs is produced. Specific enzymes for displacing the unsaturations are PDCR, PECI and ECH1.
ZN RING proteins Peroxins that have ZN RING finger with an E3 ubiqutin ligase sequence, intrinsic to the RING domain. Peroxins PEX2, PEX10 and PEX12 belong to this group, and may be involved in the protein import and PEX5 recycling. These peroxins are highly conserved throughout the evolution and, actually, PEX10 and PEX12 could be considered as markers for peroxisome.
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