Further Studies on a-Oxidation
Degradation of 2-Hydroxy Fatty Acids & Thiamine Dependence
Acta Biomedica Lovaniensia, No. 409

By Mieke Sniekers
December 2007
Leuven University Press
Distributed By Coronet Books
ISBN: 9789058676528
115 pages, Illustrated, 6 1/8 x 9 1/2"
$97.50 Paper Original


1. Mammalian fatty acid degradation and peroxisomes
2. 3-Methyl-branched and 2- hydroxyl straight chain fatty acids
2.1 Phytanic acid: the major 3-methyl-branched fatty acid
2.1.1 Origin of phytanic acid
2.1.2 Conversion of phytol to phytanic acid
2.1.3 Phytanic acid in the diet

2.2 2-Hydroxy straight chain fatty acids
2.2.1 Occurrence of 2-hydroxy fatty acids
2.2.2 Role of 2-hydroxy fatty acids in brain

3. Alpha-oxidation of 3-methyl-branched fatty acids
3.1 The alpha-oxidation pathway of phytanic acid
3.1.1 Activation and peroxisomal transport of phytanic acid
3.1.2 Hydroxylation by phytanoyl-CoA hydroxylase
3.1.3 Cleavage of the 2-hydroxy intermediate by 2-hydroxyphytanoyl-CoA lyase
3.1.4 Conversion of pristinal to pristanic acid
3.1.5 Further degradation of pristanic acid by beta-oxidation

3.2 Refsum disease
4. Alpha-oxidation of straight chain fatty acids in the brain
4.1 alpha-hydroxylation of straight chain fatty acids int he brain
4.2 alpha-oxidation of 2-hydroxy fatty acids
5. TPP dependence of alpha-oxidation



1. Materials
1.1 General
1.2 Fatty acids and derivatives
2. Animals, human tissues, cell lines and strains
3. Molecular biology techniques
3.1 Constructs
3.2 Transformation of bacteria and plasmid isolation
3.3 Eukaryotic expression of human acyl-CoA synthetases
3.4 Purification of recombinant human 2-hydroxyphytanoyl-CoA lyase
4. Metabolic studies and analytical procedures
4.1 Preparations of hepatocytes, homogenates, subcellular fractions and cell lysates
4.2 Oxidation experiments in cells and homogenates
4.3 Enzyme activity measurements
4.3.1 Acyl-CoA synthetase
4.3.2 2-hydroxyphytanoyl-Coa lyase
4.3.3 Pyruvate decarboxylase

Part 1:alpha-oxidation of 2-hydroxy fatty acids
1.1 Introduction
1.2 Results and discussion
1.2.1 Acyl-CoA synthetase
1.2.2 Cofactor requirements
1.2.3 Identification of intermediates and end products in homogenates
1.2.4 Search for the acyl-CoA synthetase catalyzing the activation fo 2-hydroxy fatty acids
1.2.5 Tissue distribution of lyase activity
1.2.6 Subcellular distribution of lyase activity
1.2.7 Identificationof 2-hydroxyphytanoyl-CoA lyase as the cleavage enzyme in the alpha-oxidation of long chain 2-hydroxy fatty acids
1.2.8 Degradation of very long chain 2-hydroxy fatty acids in intact cells

1.3 Conclusion

Part 2:Thiamine dependence of mammalian alpha-oxidation
2.1 Introduction
2.2 Results and discussion
2.2.1 Effects of thiamine depletion on fatty acid oxidation and TPP-dependent enzymes
2.2.2 Hepatic fatty acid oxidation and 2-hydroxyacyl-CoA lyase 1 activity in thiamine-deficient rats
2.2.3 Is alpha-oxidation affected in thiamine-responsive megaloblastic anemia?




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