The RELATION BETWEEN CARBOHYDRATE AND SS-Hydroxybutyric ACID UTILIZATION BY THE HEART-LUNG PREPARATION

Waters, E. T.; Fletcher, Jean Paterson; Mirsky, I. Arthur

doi:10.1152/ajplegacy.1938.122.2.542

Cited by 29 publications

(5 citation statements)

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“…As the blood level of BHB continued to rise, however, its utilization slowed and then reached a point at which further BHB administration did not increase peripheral uptake. 9,10 Such observations underlie the currently held view that hyperketonemia results when hepatic production of ketone bodies exceeds the ability of the extrahepatic tissues to remove them.…”

Section: Physiology and Metabolismmentioning

confidence: 94%

“…By accelerating the rate of carbohydrate utilization, human physical exercise, 23,28 administration of dinitrophenol or thyroid hormone to rabbits, 10 and increased bovine lactation 29 can give rise to appreciable ketosis. Pregnant women maintain higher than normal ketone levels and show an exaggerated ketogenic response to fasting.…”

Section: Effect Of Total Starvation and Carbohydrate Restriction On Bmentioning

confidence: 99%

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Ketones: Metabolism's Ugly Duckling

2003

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Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, diet-induced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders.

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Section: Physiology and Metabolismmentioning

confidence: 94%

Section: Effect Of Total Starvation and Carbohydrate Restriction On Bmentioning

confidence: 99%

Ketones: Metabolism's Ugly Duckling

2003

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“…Ketone body as a fuel for the heart has long been recognized ( 37 , 66 ). Barnes and Waters along with their associates ( 67 , 68 ) first demonstrated that the heart can use ßOHB in 1938. In 1965, Rudolph et al ( 69 ) showed that ßOHB and acetoacetate accounted for 2.6% ± 0.3% and 6.0% ± 1.0%, respectively, of the heart's total oxidative metabolism.…”

Section: Ketone Body Oxidationmentioning

confidence: 99%

Loss of Metabolic Flexibility in the Failing Heart

Karwi

Uddin

2018

Front. Cardiovasc. Med.

312

270

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To maintain its high energy demand the heart is equipped with a highly complex and efficient enzymatic machinery that orchestrates ATP production using multiple energy substrates, namely fatty acids, carbohydrates (glucose and lactate), ketones and amino acids. The contribution of these individual substrates to ATP production can dramatically change, depending on such variables as substrate availability, hormonal status and energy demand. This “metabolic flexibility” is a remarkable virtue of the heart, which allows utilization of different energy substrates at different rates to maintain contractile function. In heart failure, cardiac function is reduced, which is accompanied by discernible energy metabolism perturbations and impaired metabolic flexibility. While it is generally agreed that overall mitochondrial ATP production is impaired in the failing heart, there is less consensus as to what actual switches in energy substrate preference occur. The failing heart shift toward a greater reliance on glycolysis and ketone body oxidation as a source of energy, with a decrease in the contribution of glucose oxidation to mitochondrial oxidative metabolism. The heart also becomes insulin resistant. However, there is less consensus as to what happens to fatty acid oxidation in heart failure. While it is generally believed that fatty acid oxidation decreases, a number of clinical and experimental studies suggest that fatty acid oxidation is either not changed or is increased in heart failure. Of importance, is that any metabolic shift that does occur has the potential to aggravate cardiac dysfunction and the progression of the heart failure. An increasing body of evidence shows that increasing cardiac ATP production and/or modulating cardiac energy substrate preference positively correlates with heart function and can lead to better outcomes. This includes increasing glucose and ketone oxidation and decreasing fatty acid oxidation. In this review we present the physiology of the energy metabolism pathways in the heart and the changes that occur in these pathways in heart failure. We also look at the interventions which are aimed at manipulating the myocardial metabolic pathways toward more efficient substrate utilization which will eventually improve cardiac performance.

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“…Although the ability of the isolated heart-lung preparation to utilize ketone bodies was decribed four decades ago (Barnes, MacKay, Moe and Visscher 1938;Waters, Fletcher and Mirsky 1938), it was Bing who called attention to the fact that under in vivo conditions ketone bodies might contribute about 5% of the energy of myocardium (Bing, Siegel, Unger and Gilbert 1954). Later it was demonstrated that ketone bodies are utilized by the myocardium in preference to glucose or pyruvate (Hall l96l;Williamson and Krebs 1961;Garland, Newsholme and Randle 1964), and in preference to free fatty acids (FFA) (Garland, Newsholme and Randle l964;Little, Goto and Spitzer 1970).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Substrate Oxidation in Isolated Myocardial Cells by β-Hydroxybutyrate

Chen¹,

Wagner²,

Spitzer³

1984

Horm Metab Res

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The role of ketone bodies in myocardial substrate oxidation was examined using freshly isolated Ca2+-tolerant heart myocytes, beta-hydroxybutyrate (beta OHB) inhibited lactate oxidation by the myocytes by 30-60%, and the inhibition was concentration dependent. Palmitate oxidation was also markedly decreased, whereas octanoate oxidation was only minimally affected by the presence of beta OHB. Lactate, octanoate, or palmitate had little, if any, effect on beta OHB oxidation. beta OHB oxidation was reduced by 22-28% in myocytes isolated from chronically diabetic rats, whereas the oxidation of palmitate remained similar to the controls. However, beta OHB still inhibited palmitate oxidation to the same extent as in the control cells. Our data support the role of beta OHB as a physiologic regulator of myocardial substrate metabolism.

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The RELATION BETWEEN CARBOHYDRATE AND SS-Hydroxybutyric ACID UTILIZATION BY THE HEART-LUNG PREPARATION

Cited by 29 publications

References 0 publications

Ketones: Metabolism's Ugly Duckling

Ketones: Metabolism's Ugly Duckling

Loss of Metabolic Flexibility in the Failing Heart

Regulation of Substrate Oxidation in Isolated Myocardial Cells by β-Hydroxybutyrate

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