K. Try's research while affiliated with University of Oslo and other places
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Publications (25)
The clinical data of two patients with Refsum’s disease are presented. All the cardinal symptoms and signs were present. In addition the patients had fingernails which showed peculiar abnormalities. The dietary treatment installed to reduce the phytanic acid accumulation resulted in an unexpected severe weight reduction, rapidly increasing levels o...
1.1. Both the ldd and ddd diastereoisomers of phytanic acid accumulate in patients with Refsum's disease.Considerable differences occur in the ldd/ddd ratios of the phytanic acid in these patients, probably depending on differences in the diet.2.2. The limited degradation of phytanic acid which takes place in patients with Refsum's disease removes...
Try, K. The in vitro ω-Oxidation of Phytanic Acid and Other Branched Chain Fatty Acids by Mammalian Liver. Scand. J. clin. Lab. Invest. 22, 224-230, 1968.
Branched chain fatty acids including phytanic acid can be ω-oxidized by a combined supernatant/micro-some fraction from liver, previously shown to ω-oxidize straight chain fatty acids. Substituti...
1.1. The metabolism of β-methyl fatty acids has been studied in healthy humans as well as in patients with Refsum's disease who show phytanic acid accumulation. As a test substance 3,6-dimethyl[8-14C]octanoic acid was used. This acid possesses a methyl group in the β-position to the carboxyl group, even after an initial ω-oxidation. The medium chai...
Studies utilizing mevalonic acid-2-(14)C and D(2)O as precursors failed to provide evidence for an appreciable rate of endogenous biosynthesis of phytanic acid in a patient with Refsum's disease. Orally administered tracer doses of phytol-U-(14)C were well absorbed both by seven normal control subjects (61 to 94%) and by two patients with Refsum's...
The unsaponifiable fraction of fat from human adipose tissue contained as main hydrocarbons pristane and phytane in small amounts. The concentration of pristane varied from 6 to 33 μg/g tissue and of phytane from 2 to 6 μg/g tissue. In patients with Refsum's disease, the adipose tissue showed the same amounts of hydrocarbons as the controls.
The ability of patients with Refsum's disease to ωoxidize fatty acids has been followed by the tricaprin test during the course of lowering serum phytanic acid by dietary treatment. At high levels of phytanic acid accumulation, the test reveals an interference with the ωoxidation system. Lowering of the phytanic acid normalizes the test, indicating...
Citations
... Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a characteristic diagnostic marker of Refsum disease, which accumulates to highly elevated levels in blood and tissue due to a defective K-oxidation step in phytanoyl-CoA degradation (for review see [1,2]). Being an amphipathic compound, phytanic acid is assumed to accumulate in membranes. ...
... Until more is known about the substrate specificity of the enzymes involved in alpha oxidation of branched-chain acids, these indirect results should not be extrapolated to apply to phytanate. This is especially the case since the same group of investigators has shown that omega oxidation and alpha oxidation of the model compounds themselves is apparently suppressed in HAP patients when their phytanate levels are high but less so when they are low (30,31). Thus, it is not estalished that the apparent deficiency in alpha oxidation of the model substrate, only a minor fraction of which underwent alpha oxidation (most being degraded by omega oxidation), reflected a primary rather than a secondary effect. ...
... Disease exacerbations after weight loss or during acute illnesses and pregnancy may respond to plasmapheresis. [44][45][46] Gene therapy has been successful in restoring enzyme activity in Refsum disease in vitro. 47 ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272446515314736-1441967719827_Q64/Per-Lundberg-4.jpg)
... Phytanic acid and its metabolite pristanic acid are common 3-methyl BCFA synthesized in ruminant or derived from phytol that are bioaccumulated in the marine system from phytoplankton chlorophyll (Wanders et al., 2011a;Taormina et al., 2020). In humans, tissue phytanic acid levels are strictly derived from dietary sources as endogenous synthesis are limited (Steinberg et al., 1965). ...
... The clinical symptoms in Refsum disease, a peroxisomal α-oxidation disorder, are well known, especially night blindness and ataxia. Liver pathology is less well documented and subsequent to the discovery of the accumulation of phytanic acid in Refsum disease, and the dietary restrictions [52], the number of necropsy studies decreased while mortality dropped. In most patients 2 without dietary restriction, phytanic acid levels were elevated in the liver, as in other tissues [54][55][56][57]. ...
Reference: Hepatic dysfunction in peroxisomal disorders
... PA along with its a-oxidation product called pristanic acid [98,99] is apparently accumulated in patients suffering from RD [100,101], SLS [40,102], RCDP [103e107], chronic polyneuropathy with bilateral shortening of the proximal phalanges and ichthyosis [108], progressive ataxia and disarthria [109], infantile RD, ZDHA or neonatal adrenoleucodystrophy with characteristic incongruities [102,104,110e112] and RBC in great apes [113]. Although the methyl group at C3 position of PA makes it difficult for b-oxidation [114,115] but the NADPH dependent U-oxidation [116] suggests PA as an important biomarker to the above-mentioned patients [43,113,117e120]. ...
... The metabolic defect is an inability in the conversion of phytanic acid to alpha-hydroxy-phytanic acid. Exogenous phytanic acid accumulates in a variety of tissues including the retinal pigment epithelium which causes impairment in the night vision (Avigan et al, 1966; Eldjarn et al, 1966). Visual field impairment generally begins until 20s before the onset of neurologic involvement. ...
... l of heavy water (Sen et al. 2009). In vivo toxicity of D 2 O in humans was tested over a 4-month period when 0.5% of body water was replaced with D 2 O without any adverse effect on the recipient (Steinberg et al. 1967). ...
Reference: Deuterium and its impact on living organisms
... AKGs have some structural similarity to pristane and phytane, which are chlorophyll metabolites. Pristane and phytane are present in human adipose tissue [137], and they are incorporated into adipose tissue in rat [138]. A related metabolite, phytol, is known to induce thermogenic fat development in the mouse [139]. ...
... With regard to the synthetic substrates, some older studies by Stokke, Try, and Eldjarn (28) showing the ␣-oxidation (one carbon degradation) of 3,6-dimethyloctanoic acid in man and in kidney slices of guinea pig (26) and rat (29), and of 3,9,9-trimethyldecanoic acid in guinea pig liver (30) are called to mind. The high activity of recombinant PAHX toward 3,7-dimethyl-6-octenoyl-CoA, 3-methylnonanoyl-CoA, and 3-methylundecanoyl-CoA that we observed now fully supports this pioneering work. ...
