Chapter 5 Fatty acid oxidation and its regulation

Bremer, Jon; Osmundsen, Harald

doi:10.1016/s0167-7306(08)60123-4

Cited by 117 publications

(81 citation statements)

References 317 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under conditions where the major end-product of fatty acid oxidation is citrate, the oxidation of palmitoyl-L-carnitine is enhanced by respectively 2.5 nmol min-' mg-' and 3.5 nmol min-' mg-' (Table 2) in adults and 16-h-old mitochondria, suggesting that formation of ketone bodies from acetyl-CoA might be limiting when compared to fatty acid oxidation, as previously suggested [28]. In term-fetal liver mitochondria the oxidation of palmitoyl-L-carnitine remains lower than that in 16-h-old or adult mitochondria whatever the end-product of fatty acid oxidation: citrate or acetoacetate (Table 2).…”

Section: Oxidution Of Pulmitoyl-l-curnitinesupporting

confidence: 71%

Evidence that the development of hepatic fatty acid oxidation at birth in the rat is concomitant with an increased intramitochondrial CoA concentration

et al. 1986

View full text Add to dashboard Cite

The development of hepatic fatty acid oxidation during the perinatal period in the rat was studied using isolated mitochondria. Ketone body synthesis from substrates entering at different levels of β‐oxidation was 2–3 times lower in mitochondria isolated from term‐fetal liver than in 16‐h‐old newborn or adult liver mitochondria. The low rate of palmitoyl‐l‐carnitine oxidation in term‐fetal mitochondria was linked neither to the low capacity of the respiratory chain nor to the removal of acetyl‐CoA in the hydroxymethylglutaryl‐CoA synthase pathway. The 2.5‐times lower concentration of CoA found in term‐fetal liver mitochondria when compared to 16‐h‐old or adult liver mitochondria might be the factor responsible for the low rate of fatty acid oxidation in term‐fetal liver mitochondria.

show abstract

Section: Oxidution Of Pulmitoyl-l-curnitinesupporting

confidence: 71%

Evidence that the development of hepatic fatty acid oxidation at birth in the rat is concomitant with an increased intramitochondrial CoA concentration

et al. 1986

View full text Add to dashboard Cite

show abstract

“…Fatty acid oxidation by mitochondria is thought to be limited by (a) fatty acid supply, (b) ATP utilization and (c) (malonylCoA-inhibited) carnitine palmitoyltransferase (CPT1) (reviewed in McGarry & Foster, 1980;Bremer, 1983;Bremer & Osmundsen, 1984). In liver malonyl-CoA regulates fatty acid oxidation and is synthesized by acetyl-CoA carboxylase, and this enzyme (and therefore fatty acid synthesis and oxidation) is regulated by the level of fatty acids, citrate, glucagon and insulin.…”

Section: Control By Substrates and Productsmentioning

confidence: 99%

“…Relatively little is known about this type of control, although it is of some medical interest as some vitamins are precursors for the coenzymes. Significant control is thought to be exerted in some conditions by total intramitochondrial adenine nucleotides (Aprille, 1988), cell phosphate (Erecinska et al, 1977;Bygrave et al, 1990), extramitochondrial guanine nucleotides (Cohen et al, 1981), mitochondrial ubiquinone , Krebs cycle intermediates (Lee & Davis, 1979;Sahlin et al, 1990), and possibly cell carnitine and CoA levels (Bremer, 1983;Bremer & Osmundsen, 1984).…”

Section: Control By Moiety Pool Sizementioning

confidence: 99%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

564

308

View full text Add to dashboard Cite

We have seen that there is no simple answer to the question ‘what controls respiration?’ The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

“…We thank Pierre and Danielle Robin for the polarographic measurements of mitochondrial respiration and fatty acid oxidation. be strong inhibitors of acyl-CoA dehydrogenase (Bremer and Osmundsen, 1984).…”

Section: Cpt and 11mentioning

confidence: 99%

Hepatic ketogenesis in newborn pigs is limited by low mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity

Duée

Pégorier

Quant

et al. 1994

Biochemical Journal

View full text Add to dashboard Cite

In newborn-pig hepatocytes, the rate of oleate oxidation is extremely low, despite a very low malonyl-CoA concentration. By contrast, the sensitivity of carnitine palmitoyltransferase (CPT) I to malonyl-CoA inhibition is high, as suggested by the very low concentration of malonyl-CoA required for 50% inhibition of CPT I (IC50). The rates of oleate oxidation and ketogenesis are respectively 70 and 80% lower in mitochondria isolated from newborn-pig liver than from starved-adult-rat liver mitochondria. Using polarographic measurements, we showed that the oxidation of oleoyl-CoA and palmitoyl-L-carnitine is very low when the acetyl-CoA produced is channelled into the hydroxymethylglutaryl-CoA (HMG-CoA) pathway by addition of malonate. In contrast, the oxidation of the same substrates is high when the acetyl-CoA produced is directed towards the citric acid cycle by addition of malate. We demonstrate that the limitation of ketogenesis in newborn-pig liver is due to a very low amount and activity of mitochondrial HMG-CoA synthase as compared with rat liver mitochondria, and suggest that this could promote the accumulation of acetyl-CoA and/or beta-oxidation products that in turn would decrease the overall rate of fatty acid oxidation in newborn- and adult-pig livers.

show abstract

Chapter 5 Fatty acid oxidation and its regulation

Cited by 117 publications

References 317 publications

Evidence that the development of hepatic fatty acid oxidation at birth in the rat is concomitant with an increased intramitochondrial CoA concentration

Evidence that the development of hepatic fatty acid oxidation at birth in the rat is concomitant with an increased intramitochondrial CoA concentration

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Hepatic ketogenesis in newborn pigs is limited by low mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity

Contact Info

Product

Resources

About