The period after a meal, known as the absorptive state, lasts for 2 to 4 hours. During this time, there are temporary increases in plasma glucose, amino acids, and triacylglycerols (TAG). Chylomicrons, which are synthesized and secreted by the intestinal mucosal cells, contribute primarily to the rise in TAG levels. The pancreas responds to the increased glucose levels by secreting more insulin and less glucagon. This elevated insulin/glucagon ratio, along with the availability of circulating substrates, makes the absorptive state an anabolic period. During this time, there is increased synthesis of TAG, glycogen, and protein to replenish the body's fuel stores. Glucose is the primary fuel used by all tissues during this period, and the metabolic response of the body is mainly influenced by changes in the liver, adipose tissue, skeletal muscle, and brain. This chapter introduces an "organ map" that illustrates the movement of metabolites between tissues, aiming to provide a comprehensive and clinically useful understanding of whole-body metabolism.

Regulatory mechanisms play a crucial role in controlling the flow of intermediates through metabolic pathways. There are four main mechanisms involved: 1) substrate availability, 2) allosteric regulation of enzymes, 3) covalent modification of enzymes, and 4) induction-repression of enzyme synthesis, primarily through regulation of transcription. While these mechanisms may appear redundant at first, they operate on different timescales, allowing the body to adapt to various physiological conditions. In the absorptive state, these regulatory mechanisms ensure that the available nutrients are utilized to form glycogen, TAG, and protein.

Allosteric effectors are responsible for most allosteric changes, which typically affect rate-determining reactions. For instance, fructose 2,6-bisphosphate, an allosteric activator of phosphofructokinase-1 (PFK-1), stimulates glycolysis in the liver after a meal. On the other hand, fructose 2,6-bisphosphate acts as an allosteric inhibitor of fructose 1,6-bisphosphatase, reducing gluconeogenesis.

Covalent modification is another important regulatory mechanism. Many enzymes' activity is controlled by the addition or removal of phosphate groups from specific serine, threonine, or tyrosine residues on the protein. Kinases, such as cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and adenosine monophosphate-activated protein kinase (AMPK), add phosphate groups, while phosphatases remove them. In the absorptive state, most of the covalently regulated enzymes are in their active, dephosphorylated form. However, glycogen phosphorylase kinase, glycogen phosphorylase, and hormone-sensitive lipase (HSL) are inactive when dephosphorylated, with the exception of the phosphatase domain of bifunctional phosphofructokinase-2 (PFK-2) in the liver.

Induction and repression of enzyme synthesis also contribute to the regulation of metabolic pathways.
The Feed–Fast Cycle 24
The absorptive (well-fed) state is the 2-to 4-hour period after ingestion of a normal meal. During this interval, transient increases in plasma glucose, amino acids, and triacylglycerols (TAG) occur, the latter primarily as components of chylomicrons synthesized and secreted by the intestinal mucosal cells (see p. 228). Islet tissue of the pancreas responds to the elevated level of glucose with increased secretion of insulin and decreased secretion of glucagon. The elevated insulin/glucagon ratio and the ready availability of circulating substrates make the absorptive state an anabolic period characterized by increased synthesis of TAG and glycogen to replenish fuel stores as well as increased synthesis of protein. During this absorptive period, virtually all tissues use glucose as a fuel, and the metabolic response of the body is dominated by alterations in the metabolism of liver, adipose tissue, skeletal muscle, and brain. In this chapter, an “organ map” is introduced that traces the movement of metabolites between tissues. The goal is to create an expanded and clinically useful vision of whole-body metabolism.
II. REGULATORY MECHANISMS
The flow of intermediates through metabolic pathways is controlled by four mechanisms: 1) the availability of substrates, 2) allosteric regulation of enzymes, 3) covalent modification of enzymes, and 4) induction-repression of enzyme synthesis, primarily through regulation of transcription. Although this scheme may at first seem redundant, each mechanism operates on a different timescale (Fig. 24.1) and allows the body to adapt to a wide variety of physiologic situations. In the absorptive state, these regulatory mechanisms insure that available nutrients are captured as glycogen, TAG, and protein.
A. Allosteric effectors
Allosteric changes usually involve rate-determining reactions. For example, glycolysis in the liver is stimulated following a meal by an increase in fructose 2,6-bisphosphate, an allosteric activator of phosphofructokinase-1 ([PFK-1] see p. 99). In contrast, gluconeogenesis is decreased by fructose 2,6-bisphosphate, an allosteric inhibitor of fructose 1,6-bisphosphatase (see p. 122).
B. Covalent modification
The activity of many enzymes is regulated by the addition (via kinases, such as cyclic adenosine monophosphate [cAMP ]–dependent protein kinase A [PKA] and adenosine monophosphate–activated protein kinase [AMPK]) or removal (via phosphatases) of phosphate groups from specific serine, threonine, or tyrosine residues of the protein. In the absorptive state, most of the covalently regulated enzymes are in the dephosphorylated form and are active (Fig. 24.2). Three exceptions are glycogen phosphorylase kinase (see p. 132), glycogen phosphorylase (see p. 132), and hormone-sensitive lipase (HSL) (see p. 189), which are inactive in their dephosphorylated form. [Note: In the liver, the phosphatase domain of bifunctional phosphofructokinase-2 (PFK-2) is inactive when the protein is dephosphorylated (see p. 100).]
C. Induction and repression of enzyme synthesis