Zonation of hepatic fatty acid metabolism - The diversity of its regulation and the benefit of modeling.

A pronounced heterogeneity between hepatocytes in subcellular structure and enzyme activities was discovered more than 50years ago and initiated the idea of metabolic zonation. In the last decades zonation patterns of liver metabolism were extensively investigated for carbohydrate, nitrogen and lipid metabolism. The present review focuses on zonation patterns of the latter. We review recent findings regarding the zonation of fatty acid uptake and oxidation, ketogenesis, triglyceride synthesis and secretion, de novo lipogenesis, as well as bile acid and cholesterol metabolism. In doing so, we expose knowledge gaps and discuss contradictory experimental results, for example on the zonation pattern of fatty acid oxidation and de novo lipogenesis. Thus, possible rewarding directions of further research are identified. Furthermore, recent findings about the regulation of metabolic zonation are summarized, especially regarding the role of hormones, nerve innervation, morphogens, gender differences and the influence of the circadian clock. In the last part of the review, a short collection of models considering hepatic lipid metabolism is provided. We conclude that modeling, despite its proven benefit for understanding of hepatic carbohydrate and ammonia metabolisms, has so far been largely disregarded in the study of lipid metabolism; therefore some possible fields of modeling interest are presented.

Sodium iodoacetate as an antiglycolytic agent in blood samples.

We evaluated the effect of sodium iodoacetate on glycolysis in a series of randomly selected blood samples from patients. Glucose values for serum and for serum with added sodium fluoride (2.5 g/liter) or sodium iodoacetate (2 g and 0.5 g/liter) were compared at room temperature. Respective declines in glucose values averaged 170, 40, 30, and 30 mg/liter after 24 h. Iodoacetate-preserved (0.5 g/liter) samples showed no visible hemolysis. Results of determinations of urea with urease and of other tests on SMA 12/60 (Technicon) panels were unaffected.