Table 1.
Functions of peroxisomal enzymes
| Biochemical pathways | Enzymes1 | Features | Relevance to disease |
| β-oxidation of Straight, very long chain (≥C22) fatty acids | ACOX1, DBP, ACAA1, [SCPX] | Chain shortening of very long chain fatty acids (VLCFA), final step in the synthesis of docosohexanoic acid (DHA) | Tissue accumulation of VLCFA cause brain, nerve and adrenal damage. Deficiency of DHA affects brain function and vision |
| β-oxidation of Methyl-branched chain fatty acid (pristanic) and C27 bile acid precursors, di- and trihydroxycholestanoic acids (D/THCA) | ACOX2, DBP, SCPX | Chain shorteninig of pristanic acid and D/THCA utlizes a different oxidase than that used in straight chain shortening | Accumulation of pristanic acid affects brain and nerve. Increased D/THCA cause liver toxicity |
| β-oxidation of Dicarboxylic fatty acids | ACOX1, LBP, [DBP] ACAA1, [SCPX] | Chain shortening of dicaboxylic acids utilizes L-bifunctional protein (LBP) in contrast to DBP used in straight chain shortening | Unknown |
| α-oxidation of Methyl-branched chain fatty acid (phytanic) | PHYH | Degradation of methyl-branched phytanic acid requires an additional α- oxidation before entering the β-oxidation pathway as pristanic acid | Tissue accumulation of phytanic acid causes retinal degeneration, cerebellar ataxia, peripheral neuropathy |
| Racemization of Pristanic and D/THCA acids from (R) to (S) enantiomers | AMACR | β-oxidation requires the (S) enantiomers of pristanoyl-CoA and C27-bile acyl-CoAs | Causes tissue accumulation of (R) forms of pristanic acid and D/THCA (and secondary elevation of phytanic acid) |
| Biosynthesis of Ether phospholipids (plasmalogen) | GNPAT, AGPS, FAR1, [FAR2] | Initial steps of plasmalogen synthesis occur in the peroxisome | Deficiency causes skeletal dysplasia, cataracts, profound growth and intellectual deficiency |
| Detoxification of Glyoxylate | AGXT | Prevents the conversion of glyoxylate into the toxic metabolite, oxalate | Accumulation of oxalate results in calcium oxalate renal stones |
| Detoxification of Hydrogen Peroxide | CAT | Required for catabolism of hydrogen peroxide, produced as a by-product of oxidase enzymes | Increased oxidant damage |
| Amino acid oxidation L-Pipecolic acid and D-amino acids | PIPOX, DAO | Regulation of lysine degradation through L-pipecolic acid, and D-serine and glycine levels | Pipecolic acid levels are used as a biomarker for peroxisome dysfunction, but the relationship to disease processes is unknown |
1Redundant enzymes are in brackets []. Full enzyme names: ACOX1, acyl-CoA oxidase 1; ACOX2, acyl-CoA oxidase 2;DBP, D-bifunctional protein; LBP, L-bifunctional protein; ACAA1, acetyl-CoA acyltransferase 1 (peroxisomal thiolase); SCPX, sterol carrier protein-peroxisomal thiolase; PHYH, phytanyl-CoA hydroxylase; AMACR, alpha-methylacyl-CoA racemase; GNPAT, glyceronephosphate O-acyltransferase or dihydroxyacetonephosphate acyltransferase); AGPS, alkylglycerone phosphate synthase or alkyl-dihydroxy-acetonephosphate synthase); FAR1, fatty acyl-CoA reductase; FAR2, fatty acyl-CoA reductase 2; AGXT, alanine-glyoxylate aminotransferase; CAT, catalase; PIPOX, L-pipecolic acid oxidase; DAO, D-amino acid oxidase.