Peroxisomes are ubiquitous subcellular organelles. They contain
catalase and
hydrogen peroxide-producing
oxidases like
fatty acyl-CoA oxidase. The latter
enzyme is part of a special
fatty acid beta-oxidation system which shortens long-chain
fatty acids. The middle-chain
acids formed are subsequently degraded by mitochondria. The capacity to remove very long
fatty acids and trans-unsaturated
acids found in hydrogenated
oils is restricted to peroxisomes. Essentially, the peroxisomal beta-oxidation system is not constitutive but inducible by certain hypolipidaemic compounds which are distinguished by their capacity to lead to proliferation of peroxisomes.
Thyroid hormones as well as prolonged exposure to cold and high fat diets, esp. with long-chain
unsaturated fatty acids, also induce beta-oxidation and peroxisome proliferation. Two other beta-oxidative reactions namely the removal of the
cholesterol side-chain, leading to the formation of
bile acids, and the degradation of
dicarboxylic acids as formed by omega-oxidation of
fatty acids were shown to be connected with peroxisomes. Presumably also 3-hydroxy-3-methyl-glutaryl-CoA
reductase, the key
enzyme of
cholesterol biosynthesis exists in a peroxisomal moiety.
NADPH consumed in this reaction (and in the
dihydroxyacetone phosphate pathway of glycerolipid synthesis) might be provided by
glucose-6-phosphate dehydrogenase which was recently also found in peroxisomes. Peroxisomes are indispensable in forming saturated
ether lipids and
plasmalogens because alkyldihydroxyacetone
phosphate synthase is a membrane
enzyme exclusively located in peroxisomes. Certain other
enzymes of the
dihydroxyacetone phosphate pathway of glycerolipid synthesis are also found in peroxisomes. Because of the combination of
oxidases like
fatty acyl-CoA oxidase and
catalase and the feasibility of reoxidising
NADH within the peroxisomes the aerobic metabolism of peroxisomes is energy-wasting. Therefore they might be important in chemical thermogenesis and in the control of
body weight. For all these reasons peroxisomes must be essential for human metabolism. This is further demonstrated by genetically caused disorders: Total absence of peroxisomes is connected with the fatal cerebro-hepatorenal
Zellweger syndrome. Defective peroxisomal beta-oxidation is manifested in
Schilder's disease (
adrenoleukodystrophy) characterized by accumulation of very long
fatty acids. Peroxisomes perform a number of complementary and auxiliary reactions in general cell metabolism, in particular the cata- and anabolism of certain
lipids, and therefore deserve consideration in clinical chemistry.