Kaare R. Norum

Transport and storage of vitamin A

The requirement of vitamin A (retinoids) for vision has been recognized for decades. In addition, vitamin A is involved in fetal development and in the regulation of proliferation and differentiation of cells throughout life. This fat-soluble organic compound cannot be synthesized endogenously by humans and thus is an essential nutrient; a well-regulated transport and storage system provides tissues with the correct amounts of retinoids in spite of normal fluctuations in daily vitamin A intake. An overview is presented here of current knowledge and hypotheses about the absorption, transport, storage, and metabolism of vitamin A. Some information is also presented about a group of ligand-dependent transcription factors, the retinoic acid receptors, that apparently mediate many of the extravisual effects of retinoids.

Determination of Lecithin: Cholesterol Acyltransfer in Human Blood Plasma

AbstractA method for determining lecithin: cholesterol acyltransferase (LCAT) activity is presented. Trace amounts of labelled cholesterol are added to serum or plasma. During a preincubation time in which the LCAT is inhibited by a disulphide, the tracer equilibrates with endogenous lipoprotein cholesterol. The enzyme is reactivated by excess of thiol. The presented method seems to be a good measure for the in vivo blood plasma cholesterol esterification rate as only autologous, non-heated lipoproteins are used in the assay.

The Metabolic Role of Lecithin: Cholesterol Acyltransferase: Perspectives from Pathology

Publisher Summary This chapter discusses the metabolic role of enzyme lecithin called cholesterol acyltransferase (LCAT). The role of the LCAT reaction is to prevent unesterified cholesterol, derived mainly from the surfaces of chylomicrons and very low density lipoproteins, from accumulating in the plasma. This is successfully accomplished only when the LCAT reaction balances the mechanisms that increase plasma unesterified cholesterol. A balance does not occur in familial LCAT deficiency because the enzyme is absent. It does not occur in cholesterol-fed guinea pigs because unusually large amounts of dietary unesterified cholesterol enter the plasma through inadequate control in either the intestine or the liver. It does not occur in cholestasis because phospholipid bilayers are formed and promote the accumulation of unesterified cholesterol in plasma through increased hepatic biosynthesis. Unesterified cholesterol becomes associated with the surfaces of newly formed lipoproteins by physical equilibration within the cells of the intestinal mucosa and the liver. The function of the LCAT reaction is to transport unesterified cholesterol synthesized in peripheral tissues to the liver.

Familial Plasma Lecithin: Cholesterol Acyltransferase Deficiency Biochemical Study of a New Inborn Error of Metabolism

Three adult sisters with a new inborn error in lipid metabolism have been studied. They had an almost complete lack of esterified cholesterol in plasma, and a high concentration of plasmafree cholesterol. The plasma concentrations of lecithin were high and of lysolecithin low. These abnormalities were found to be associated with an absence of plasma lecithin: cholesterol acyltransferase. No inhibitors of this enzyme could be demonstrated in the plasma of the patients. The small amounts of cholesterol esters found in the plasma of the patients were found to be formed during intestinal absorption of cholesterol. The two eldest patients had lipemic plasma. The fatty acid composition of the triglycerides were normal. Electrophoresis of the plasma lipoproteins revealed a pathological pattern: no α- and no pre- β-lipoproteins could be demonstrated. Immunoelectrophoresis also revealed an α-lipoprotein deficiency. The data obtained in the present study strongly suggest that the plasma cholesterol esterification r...

Palmityl-coa:carnitine palmityltransferase: Purification from calf-liver mitochondria and some properties of the enzyme

1. 1. Palmityl-CoA: carnitine palmityltransferase has been purified from calf-liver mitochondria. The specific activity is about 22 times that in total homogenate of the liver. The purified preparation contains no palmityl-CoA hydrolase (EC 3.1.2.2). 2. 2. The Km-values in the reaction: palmityl-CoA + carnitine ⇌ palmitylcarnitine + CoA, were found to be: CoA, 4.5·10−5M; palmityl-CoA, 3.1·10−5 M;L-carnitine, 2.1·10−3M; and L-palmitylcarnitine, 1.7·10−4M. Only the L-isomers of carnitine and its acyl esters were found to be enzymically active. 3. 3. The equilibrium constant was found to be 0.45. This states that the o-palmityl ester of palmitylcarnitine has a high group potential. 4. 4. The enzyme exhibits maximum activity between pH 7.0 and 8.2. 5. 5. The activity of the enzyme increases with increasing chain length of the acyl group. 6. 6. It is proposed that the enzymic reaction represents an easy method for the generation of palmityl-CoA in coupled enzyme systems, or for the preparation of pure palmityl-CoA in substrate amounts.

Methylmalonic acidemia. A new inborn error of metabolism which may cause fatal acidosis in the neonatal period.

A new inborn error of metabolism characterized by severe metabolic acidosis, polyuria, dehydration, emaciation and the urinary excretion of large amounts of methylmalonic acid is described. Two siblings of the patient have died in the neonatal period with clinical symptoms strongly resembling those of our patient. Our studies indicate that the metabolic block is located in the degradation of methylmalonic acid to succinic acid.Valine was shown to be a precursor of methylmalonic acid in accordance with the known metabolic formation of this acid. Small amounts of valine were metabolized to CO2, suggesting that the metabolic defect is incomplete. The blood concentration, body burden, distribution volume, serum half life and renal clearance of methylmalonic acid were determined.Treatment with cyanocobalamin and with cobamide coenzyme did not appear to influence the course of the disease.A diet low in isoleucine, valine, threonine and methionine significantly reduced the urinary excretion of methylmalonic acid...

Relationships between plasma levels of organochlorines, retinol and thyroid hormones from polar bears (Ursus maritimus) at Svalbard.

Associations were determined between retinol and the thyroid hormones thyroxine (T4) and triiodothyronine (T3), respectively, and the organochlorine contaminants (OCs) polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis-(4-chlorophenyl)ethylene (DDE), hexachlorobenzene (HCB), and hexachlorocyclohexanes (HCHs) in blood plasma from polar bears ( Ursus maritimus ) caught at Svalbard. The blood samples were collected from free-ranging polar bears of different age and sex in 1991-1994. The retinol concentration and the ratio of total T4 (TT4) to free T4(FT4) (TT4/FT4 ratio) decreased linearly with increasing concentrations of PCBs and HCB. Retinol was also negatively associated with HCHs, while the TT4/FT4 ratio was positively associated with DDE. The concentrations of retinol and thyroid hormones were significantly higher in females than in males. However, the TT4/FT4 and TT3/FT3 ratios were significantly higher in males than in females. The concentrations of thyroid hormones were negatively correlated with age in male bears, while in females, thyroid hormones did not change with age. The OCs were found to explain 12, 30, and 7% of the variation of retinol concentrations and the TT4/FT4 and TT3/FT3 ratios, respectively, after correcting for age and sex. The potential consequence of these associations for the individual and the population is unknown.

Uptake and degradation of 125I-labelled asialo-fetuin by isolated rat hepatocytes.

125I-Labelled asialo-fetuin was taken up by isolated rat hepatocytes by a saturable process. Half maximum uptake was seen at about 3 - 10(-8) M asialo-fetuin. Non-parenchymal liver cells did not take up asialo-fetuin in vitro. Rate of uptake of asialo-fetuin exceeded rate of degradation at all concentrations of asialo-fetuin tested. Asialo-fetuin consequently accumulated in the cells until the extracellular supply was exhausted. Asialo-fetuin degradation could be studied without concurrent uptake by incubating cells, previously exposed to asialo-fetuin, in asialo-fetuin-free medium. Degradation, as evidenced by increase in acid-soluble radioactivity, was inhibited by NH4Cl and chloroquine. The change with time in the intracellular distribution pattern of radioactivity in cells that had been exposed to 125I-labelled asialo-fetuin for 10 min was examined by means of differential centrifugation. Initially, the radioactivity was found mostly in the microsomal fraction. 60 min after the exposure to labelled protein, the distribution pattern of radioactivity resembled that of the lysosomal enzyme beta-acetylglucosaminidase. The possibility that asialo-fetuin digestion takes place in lysosomes is discussed.

Familial plasma lecithin: cholesterol acyltransferase deficiency.

A woman with familial plasma lecithin: cholesterol acyltransferase (L.C.A.T.) deficiency showed, like the other reported cases, obvious corneal opacity, proteinuria, and moderate anaemia with a slight haemolytic component. In the plasma the concentrations of free cholesterol, triglycerides, and lecithin were high, and those of esterified cholesterol, lysolecithin, and alphalipoprotein were low. L.C.A.T. activity in plasma was 10% of normal. The heparin-induced lipolytic activity in plasma was reduced. The erythrocyte lipid pattern was abnormal and showed the same pattern as earlier described in L.C.A.T. deficiency. The patients brother also probably suffered from the disease and died in uraemia. These are the fourth and fifth known patients with L.C.A.T. deficiency, the first one reported in a male, and the first one with a fatal outcome.

The submitochondrial distribution of acid: CoA ligase (AMP) and palmityl-CoA: Carnitine palmityltransferase in rat liver mitochondria

Abstract Recently a method for the separation of the outer and inner mitochondrial membranes has been worked out in the Wenner-Green Institute, Stockholm, Sweden (Sottocasa et , al 1966) . We have used this method for the study of the intramitochondrial localization of acyl-CoA synthetase (acid: CoA ligase AMP, EC 6.2.1.3) and carnitine palmityltransferase (palmityl-CoA: carnitine palmityltransferase, EC 2.3.1…) in relation to mitochondrial marker enzymes. Results are presented which indicate that acyl-CoA synthetase is confined to the outer mitochondrial membrane, carnitine palmityltransferase and β-hydroxybutyrate dehydrogenase (EC 1.1.30) to the inner mitochondrial membrane, and glutamate dehydrogenase (EC 1.4.1.3) to the matrix of the mitochondrion.