Liver Metabolism

One of the most important roles of the liver is to serve as a "glucostat," monitoring and stabilizing blood glucose levels. To meet its internal energy needs, the liver can use a variety of fuel sources, including glucose, fatty acids, and amino acids. A primary role of liver is the synthesis of fuel components for use by other organs. Most of the low-molecular-weight metabolites that appear in the blood through digestion are taken up by the liver for this metabolic processing. Compounds synthesized in the liver include the following:

> 1. Fatty acids - The liver is a major site for fatty acid synthesis.

> 2. Glucose - The liver produces glucose, both from its own glycogen stores and from gluconeogenesis, the latter using lactate and alanine from muscle, glycerol from adipose tissue, and the amino acids not needed for protein synthesis. An important role of liver is to buffer the level of blood glucose. It does this largely through the action of glucokinase, an enzyme peculiar to liver, with a high K M (about 10 mm) for glucose, and partly through a high-K M transport protein, the glucose transporter. Thus, liver is unique in being able to respond to high blood glucose levels by increasing the uptake and phosphorylation of glucose, which results eventually in its deposition as glycogen. Glucose-6-phosphate accumulation activates the D form of glycogen synthase. In addition, glucose itself binds to glycogen phosphorylase a, increasing the susceptibility of phosphorylase a to dephosphorylation (see Figure 13.18), with consequent inactivation. Thus, in addition to hormonal effects (see here), the liver senses the fed state and acts to store fuel derived from glucose. The liver also senses the fasted state and increases the synthesis and export of glucose when blood glucose levels are low. (Other organs also sense the fed state, notably the pancreas, which adjusts its glucagon and insulin outputs accordingly.)

> 3. Ketone bodies - Ketone bodies are also manufactured largely in the liver. The level of malonyl-CoA in liver, which is related to the energy status of the cell, determines the fate of fatty acyl-CoAs. When fuel is abundant, malonyl-CoA accumulates and inhibits carnitine acyltransferase I, preventing the transport of fatty acyl-CoAs into mitochondria for -oxidation and ketogenesis. On the other hand, shrinking malonyl-CoA pools signal the cells to transport fatty acids into the mitochondria, for generation of energy and fuels.

See also: Biological Fuel, Hormonal Regulation of Fuel Metabolism, Figure 23.4