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Biomedical subjects

P S West

Publications and source records attributed to P S West.

5 recordsLinked to original sources

Proline and hepatic lipogenesis.

The effects of proline on lipogenesis in isolated rat hepatocytes were determined and compared with those of lactate, an established lipogenic precursor. Proline or lactate plus pyruvate increased lipogenesis (measured with 3H2O) in hepatocytes from fed rats depleted of glycogen in vitro and in hepatocytes from starved rats. Lactate plus pyruvate but not proline increased lipogenesis in hepatocytes from starved rats. ( - )-Hydroxycitrate, an inhibitor of ATP-citrate lyase, partially inhibited incorporation into saponifiable fatty acid of 3H from 3H2O and 14C from [U-14C]lactate with hepatocytes from fed rats. Incorporation of 14C from [U-14C]proline was completely inhibited. Similar complete inhibition of incorporation of 14C from [U-14C]proline by ( - )-hydroxycitrate was observed with glycogen-depleted hepatocytes or hepatocytes from starved rats. Inhibition of phosphoenolpyruvate carboxykinase by 3-mercaptopicolinate did not inhibit the incorporation into saponifiable fatty acid of 3H from 3H2O or 14C from [U-14C]proline or [U-14C]lactate. Both 3-mercaptopicolinate and ( - )-hydroxycitrate increased lipogenesis (measured with 3H2O) in the absence or presence of lactate or proline with hepatocytes from starved rats. The results are discussed with reference to the roles of phosphoenolpyruvate carboxykinase, mitochondrial citrate efflux, ATP-citrate lyase and acetyl-CoA carboxylase in proline- or lactate-stimulated lipogenesis.

Animals↗

Odd-carbon fatty acid metabolism in hepatocytes from starved rats.

The metabolism of odd-chain fatty acids was investigated in hepatocytes from 24 h-starved rats. Rates of glucose and 14CO2 production from [1-14C]propionate, [1-14C]valerate and [1-14C]nonanoate were maximal at 0.1 mM. Glucose production was greater with propionate as substrate than with valerate or nonanoate. Ketone body, lactate and pyruvate release were not affected by addition of the odd carbon fatty acids. It is concluded that hepatic odd-chain fatty acid metabolism in starvation is partly oxidative and partly gluconeogenic. Vasopressin and angiotensin II stimulated 14CO2 production from [1-14C] valerate and [1-14C]nonanoate but not from [1-14C]propionate and [1-14C]oleate in hepatocytes from starved rats. Nonanoate and valerate generate acetyl-CoA and propionyl-CoA, whereas oleate or propionate produce acetyl CoA and propionyl-CoA respectively. Given this stoichiometry, it is inferred that in hepatocytes from starved rats there must be an input of a tricarboxylic acid cycle intermediate to permit expression of the hormonal sensitivity.

Angiotensin II↗

Influence of acetylator phenotype on antidepressant effects of phenelzine.

Acetylator phenotype, determined by blood levels after sulphadimidine, was related to outcome in a controlled trial of phenelzine in patients with depression and mixed anxiety depression. Slow acetylators showed more improvement and greater phenelzine-placebo differences than did fast acetylators, at two, four and six weeks. A tendency towards faster acetylation was observed in subjects with previous increased alcohol intake. Acetylator phenotype was not related to other symptom, diagnostic or history data.

Acetylation↗

Comparison of simple screening tests for fat malabsorption.

Three tests were evaluated as screening procedures for fat malabsorption--namely, measurement of serum optical density, serum triglyceride concentration, and 14CO2 breath excretion after the administration of a 60 g fat meal containing 10 muCi glycerol tri[1-14C]oleate. The results of these tests were compared with fat excreted in a three-day faecal collection after adjustment for completeness of collection as assessed by using non-absorbable radio-opaque markers. Fifty-two patients with various symptoms and eight normal subjects were studied. The maximum increase in serum optical density or triglyceride concentration above the fasting value discriminated poorly between subjects with normal and increased adjusted faecal fat excretion. In contrast, seven- or eight-hour cumulative 14CO2 breath excretion provided good discrimination with only four (7%) false-positive and no false-negative results. The simplicity and convenience of breath analysis make it an attractive alternative to analysis of faecal fat excretion in screening for fat malabsorption.

Adolescent↗