Chapter 9 Mechanism of bile acid biosynthesis in mammalian liver

Björkhem, Ingemar

doi:10.1016/s0167-7306(08)60685-7

Cited by 157 publications

(105 citation statements)

References 228 publications

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“…These pathways are separately regulated. The rate-limiting enzyme in bile acid synthesis in the liver is cholesterol 7a-hydroxylase (Bjo Èrkhem, 1985). When the activity of cholesterol 7a-hydroxylase is high the neutral pathway is considered to be the most important, and when the activity of 7a-hydroxylase is low the acidic pathway is considered to be the most important (Axelson & Sjo Èvall, 1990).…”

Section: Discussionmentioning

confidence: 99%

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects

Ekwall

Björck

et al. 1998

Eur J Clin Nutr

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Objective: To study the short-term effect of resistant starch (RS) from retrograded high-amylose corn starch (HACS) on the excretion of bile acids and nutrients from the small bowel in humans. Design: Seven healthy ileostomists were given a controlled, constant diet during three days. On days 2 and 3, 100 g/d of one of two test-productsÐdrum-dried ordinary corn starch and autoclaved retrograded HACS, providing 5 and 39 g RS/d, respectivelyÐwas given, in random order. Ileostomy ef¯uents were collected for 24 h per day and analysed for wet weight, dry weight, energy, bile acids and nutrients. Settings: In-patient study at the metabolic ward, Department of Clinical Nutrition, Sahlgrenska University Hospital, Go Èteborg. Results: Consumption of retrograded HACS caused (1) a 42% lower mean excretion of cholic acid (P 0.024); (2) a 42% lower mean wet weight concentration of bile acids (P`0.001); (3) a 70% increased excretion of dry weight (P 0.001); and (4) a 41% increased excretion of energy (P 0.036) compared with consumption of drum-dried ordinary corn starch. Conclusion: The reduced ileal excretion and concentration of cholic acid would be protective regarding colon cancer risk in addition to the increased fermentation substrate provided by RS and other energy-yielding components.

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Section: Discussionmentioning

confidence: 99%

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects

Ekwall

Björck

et al. 1998

Eur J Clin Nutr

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“…Normally all-bile acids are minor constituents in mammals, although in some lower vertebrates they are major bile acids (34). Several different pathways have been proposed for the formation of allo-bile acids in mammals (1). One of these includes the action of intestinal micro-organisms.…”

Section: Serum Bile Acid Analysismentioning

confidence: 99%

“…The postnatal increase in bile secretion that occurs in the human and other species depends largely on the coordinate maturation of hepatic biosynthetic and transport mechanisms for bile acids. Pathways of bile acid synthesis from cholesterol in adults are relatively well defined (1) and involve various modifications of the steroid nucleus, including the conversion of the 3,3-hydroxy-A5 structure of this sterol to a 3a-hydroxy-5f3(H) structure, which is common to chenodeoxycholic and cholic acids, the principal bile acids in man. Hydroxylations at positions C-7 of the steroid nucleus, and C-12 for cholic acid, and oxidation of the side chain are also required.…”

Section: Introductionmentioning

confidence: 99%

Delta 4-3-oxosteroid 5 beta-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis.

Setchell¹,

Suchy²,

Welsh³

et al. 1988

J. Clin. Invest.

237

155

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A new inborn error in bile acid synthesis, manifest in identical infant twins as severe intrahepatic cholestasis, is described involving the A4-3-oxosteroid 5,#-reductase catalyzed conversion of the key intermediates, 7a-hydroxy4-cholesten-3-one and 7a,12a-dihydroxy4-cholesten-3-one for chenodeoxycholic and cholic acid synthesis, to the respective 3a-hydroxy-5#(H) products. This defect was detected by fast atom bombardment ionization-mass spectrometry from an elevated excretion and predominance of taurine conjugated unsaturated hydroxy-oxo-bile acids. Gas chromatography-mass spectrometry confirmed these to be 7a-hydroxy-3-oxo-4-cholenoic and 7a,12a-dihydroxy-3-oxo4-cholenoic acids (75-92% of total).Fasting serum bile acid concentrations were > 37 Amol/liter; chenodeoxycholic acid was the major bile acid, but significant amounts of allo(5a-H)-bile acids (-30%) were present. Biliary bile acid concentration was < 2 ,mol/liter and consisted of chenodeoxycholic, allo-chenodeoxycholic, and allo-cholic acids. These biochemical findings, which were identical in both infants, indicate a defect in bile acid synthesis involving the conversion of the A4-3-oxo-C27 intermediates into the corresponding 3a-hydroxy-50(H)-structures, a reaction that is catalyzed by a A4-3-oxosteroid-5j0 reductase enzyme. This defect resulted in markedly reduced primary bile acid synthesis and concomitant accumulation of A4-3-oxo-and allo-bile acids. These findings indicate a pathway in bile acid synthesis whereby side chain oxidation can occur despite incomplete alterations to the steroid nucleus, and lend support for an active A4-3-oxosteroid 5a-reductase catalyzing the conversion of the A4-3-oxosteroid intermediates to the respective 3a-hydroxy5a(H)-structures.

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“…Although peroxisomes were long believed to have only a minor function in mammalian metabolism, it has become clear in recent years that these organelles play an important role in a number of metabolic pathways including fatty acid ,B-oxidation, ether-phospholipid biosynthesis and bile acid biosynthesis (for reviews see [1][2][3][4]. The importance ofperoxisomes in man can be gauged from the existence of a group of genetic diseases caused by an impairment in one or more peroxisomal functions (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Peroxisomal fatty acid beta-oxidation in relation to the accumulation of very long chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders.

Wanders¹,

Roermund²,

Wijland³

et al. 1987

J. Clin. Invest.

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The peroxisomal oxidation of the long chain fatty acid palmitate (C16:0) and the very long chain fatty acids lignocerate (C24:0) and cerotate (C26:0) was studied in freshly prepared homogenates of cultured skin fibroblasts from control individuals and patients with peroxisomal disorders. The peroxisomal oxidation of the fatty acids is almost completely dependent on the addition of ATP, coenzyme A (CoA), Mg2+ and NAD'.However, the dependency of the oxidation of palmitate on the concentration of the cofactors differs markedly from that of the oxidation of lignocerate and cerotate.The peroxisomal oxidation of all three fatty acid substrates is markedly deficient in fibroblasts from patients with the Zellweger syndrome, the neonatal form of adrenoleukodystrophy and the infantile form of Refsum disease, in accordance with the deficiency of peroxisomes in these patients. In fibroblasts from patients with X-linked adrenoleukodystrophy the peroxisomal oxidation of lignocerate and cerotate is impaired, but not that of palmitate. Competition experiments indicate that in fibroblasts, as in rat liver, distinct enzyme systems are responsible for the oxidation of palmitate on the one hand and lignocerate and cerotate on the other hand. Fractionation studies indicate that in rat liver activation of cerotate and lignocerate to cerotoyl-CoA and lignoceroyl-CoA, respectively, occurs in two subcellular fractions, the endoplasmic reticulum and the peroxisomes but not in the mitochondria. In homogenates of fibroblasts from patients lacking peroxisomes there is a small (25%) but significant deficiency of the ability to activate very long chain fatty acids. This deficient activity of very long chain fatty acyl-CoA synthetase is also observed in fibroblast homogenates from patients with X-linked adrenoleukodystrophy. We conclude that X-linked adrenoleukodystrophy is caused by a deficiency of peroxisomal very long chain fatty acyl-CoA synthetase.

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Chapter 9 Mechanism of bile acid biosynthesis in mammalian liver

Cited by 157 publications

References 228 publications

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects

Delta 4-3-oxosteroid 5 beta-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis.

Peroxisomal fatty acid beta-oxidation in relation to the accumulation of very long chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders.

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