PubMed Health⌕ Search

Biomedical subjects

D W Pethick

Publications and source records attributed to D W Pethick.

24 records · Page 2Linked to original sources

The metabolism of circulating non-esterified fatty acids by the whole animal, hind-limb muscle and uterus of pregnant ewes.

1. The over-all and regional metabolism of non-esterified fatty acids (NEFA) was studied using a combination of isotopic and arteriovenous-difference techniques. 2. There was a common linear relationship, whether stearic, palmitic or oleic acids were used as tracer, between the arterial NEFA concentration and the rates of entry and oxidation. 3. Assuming that the tracer used reflected the metabolism of all the NEFA, the total entry rate in fed and fasted pregnant ewes was (mean +/- SE) 0.44 +/- 0.02 and 0.55 +/- 0.07 mmol/h per kg body-weight respectively. Oxidation of NEFA contributed (mean +/- SE) 34 +/- 5 and 58 +/- 7% to the respiratory carbon dioxide in fed and fasted animals, this accounting for (mean +/- SE) 46 +/- 6 and 59 +/- 3% of the respective entry rates. 4. Hind-limb muscle both utilized and produced NEFA. The mean gross fractional extraction (calculated from isotopic uptake) was (mean +/- SE) 9 +/- 1%. Gross utilization of any NEFA and appearance of 14CO2 across the muscle were linearly related to the arterial concentration of tracer fatty acid, irrespective of whether this was oleate or stearate. The amount of 14CO2 appearing was consistent with (mean +/- SE) 54 +/- 8% of the CO2 produced by the hind-limb being derived from NEFA oxidation. 5. Infused NEFA were partly converted to ketone bodies. Uptake and oxidation in the hind-limb of ketones formed in the liver could account for approximately 20% of the 14CO2 apparently produced in muscle from NEFA. Correction for this reduces the proportion of CO2 derived from NEFA to 43%. There was some indication that ketones were also produced from NEFA in the hind-limb. 6. NEFA were not a significant energy source for the gravid uterus. 7. An over-all view of energy sources for the whole animal and for hind-limb muscle in normal and fasted pregnant sheep was presented.

Animals↗

Acetate metabolism in lactating sheep.

1. The metabolism of acetate, glucose and D(-)-3-hydroxybutyrate was studied in lactating and non-lactating sheep in vivo. Special consideration was given to the utilization by hind-limb muscle in both groups of sheep and the uptake of nutrients by the lactating mammary gland was also measured. 2. The entry of acetate into the circulation (mmol/h per kg body-weight) was similar in all experimental animals at a given arterial concentration of acetate. However, normal lactation was associated with a reduced extraction of acetate by muscle and the 'spared' acetate was comparable with that removed by the udder. Feeding lactating ewes a 700 g concentrate/kg ration tended to prevent this redistribution of acetate utilization. 3. The muscles of non-lactating ewes utilized sufficient glucose, when corrected for lactate release, to account for 57% of the oxygen utilization by muscle. In lactation this fell to 32% largely because of an increased lactate production. D(-)-3-Hydroxybutyrate utilization by muscle accounted for 16-17% of the O2 consumed by the muscle in non-lactating and lactating sheep. 4. Lactating mammary gland metabolism in sheep was similar to published values for dairy cows and goats. Thus the extraction (%) of glucose, O2, acetate and D(-)-3-hydroxybutyrate was 25, 28, 62 and 53 respectively. Blood flow was 529 ml/min per kg udder and the ratio, blood flow: milk flow was 475. glucose used by the udder relative to the whole animal utilization rate may be less in sheep than in cows and goats, but the comparable proportion for acetate is as large or larger than in these species.

3-Hydroxybutyric Acid↗

Metabolism of ketone bodies in pregnant sheep.

A combination of isotope-dilution and arteriovenous-difference techniques was used to determine the significance of ketones to energy homoeostasis in fasted pregnant ewes. 2. There was incomplete interconversion of D(-) 3-hydroxybutyrate (3HB) and acetoacetate (AcAc) and therefore neither entry rate nor oxidation of total ketone bodies could be estimated by assuming circulating ketone bodies represent a single metabolic compartment. Total ketone body metabolism was satisfactorily summarized using a three-compartment model. In fasted pregnant ewes the mean entry rate of total ketones was 1 mmol/h per kg body-weight and of the ketones entering the circulating 87% were promptly oxidized to carbon dioxide accounting for 30% of the total CO2 production. 3. Ketone bodies are readily utilized by hind-limb skeletal muscle such that if completely oxidized, 18 +/- 4 and 48 +/- 3% of the oxygen utilized could be accounted for in fed and fasted pregnant ewes respectively. For both 3HB and AcAc there was a hyperbolic relationship between utilization and arterial concentration. The apparent Michaelis constant (Km) values were 0.55 and 1.42 mM respectively and the maximum velocity (Vmax) 2.9 and 5.6 mmol/h per kg muscle. The arterial concentration of AcAc is always below the Km value and this limits the utilization rate. THe D(-) 3HB concentration however, may surpass that required for maximum utilization and ketoacidosis may be a consequence of this. 4. A two-compartment model was used to analyse ketone body metabolism by hind-limb skeletal muscle. The results suggested substantial interconversion and production of AcAc and 3HB. 5. The pregnant uterus utilized 3HB which if completely oxidized accounted for 12 +/- 2 (fed) and 25 +/- 4 (fasted) % of its O2 consumption. At least 64% of the net 3HB utilized was oxidized. AcAc was not utilized in significant quantitites.

Animals↗

Acetate supply and utilization by the tissues of sheep in vivo.

1. The supply and utilisation of acetate has been estimated simultaneously in the whole animal and tissues of sheep using a combination is isotope-dilution and arteriovenous-difference techniques. Animals were made alloxani-diabetic and acetate metabolism was compared when stabilized to normal metabolite levels with insulin (ITA sheep) and when food and insulin had been withdrawn for 36 h (fasted, diabetic sheep). 2. Acetate was simultaneously produced and utilized by all tissues. The exogenous (or gut) supply of acetate was the most important determinant of circulating acetate level. Endogenous acetate was produced mainly in the liver; 77 and 94% in fasted, diabetic and ITA sheep respectively. The production of endogenous acetate remained fairly constant and was not related to ketogenesis, which supports the idea that circulating acetate is largely a produce of fermentation. The liver, gut and muscle utilized 17, 25 and 54% respectively (96% total) of the acetate entry rate in ITA sheep; a similar percentage utilization was found in fasted, diabetic sheep. 3. Acetate is largely oxidized to carbon dioxide in the gut and muscles of sheep and may account for 30-40% of their oxidative metabolism. This figure is similar to that for the whole animal. The total acetate taken up by the liver could account for 30% of the oxygen consumption; however, the liver may not directly oxidize all the utilized acetate. 4. The over-all conclusion from this study is that acetate is largely of dietary origin and the major factor determining its rate of utilization is the arterial concentration.

Acetates↗