FFAs are the most efficient type of fuel when it comes to producing ATP molecules per carbon of fuel. However, during the digestive phase, FFAs compete with glucose utilization in the mitochondria. Elevated levels of FFAs during this phase can result in a higher and longer-lasting surge in glucose, leading to hyperglycemia. To prevent most of the FFAs from entering the bloodstream, they are reesterified into TG and packaged into chylomicrons within the intestinal enterocyte. These chylomicrons are secreted, enter lymphatic vessels, and eventually enter the blood. Once in the circulation, chylomicrons transport FFAs (as TG) to the adipose tissue. In the adipocytes, the FFAs are released from chylomicron-associated TG through lipolysis, taken in by the adipocytes, and reesterified as intracellular TG for storage.

During the fasting phase, hepatocytes, skeletal myocytes, and adipocytes function independently of each other. However, in this phase, the actions of these three cell types become highly integrated to maintain adequate blood glucose levels and provide alternative energy substrates for each type of cell. Cells without mitochondria, such as erythrocytes, and cells of the central nervous system require glucose for ATP production throughout all metabolic phases. Therefore, the body must maintain blood glucose levels above 60 mg/dL even days or weeks after the last food intake. One exception to this is the brain, which can utilize KBs (discussed later) during a prolonged fasting phase.

Two main processes contribute to the maintenance of blood glucose during the fasting phase: hepatic glucose production and glucose sparing. Hepatic glucose production is based on two metabolic pathways. The first is the rapid breakdown of glycogen known as glycogenolysis. Hepatocytes possess the enzyme glucose-6-phosphatase (G6Pase), which allows them to convert G6P back into glucose. This glucose can then exit the cell through a bidirectional GLUT transporter. However, the release of glucose from glycogenolysis is relatively short-lived as the liver glycogen supply becomes depleted after approximately 8 hours. The second metabolic contribution to hepatic glucose production during the fasting phase is gluconeogenesis. Gluconeogenesis is a gradual process that starts slower than glycogenolysis but continues uninterrupted throughout the fasting phase. Precursors like lactate, "gluconeogenic" amino acids, and glycerol are required for gluconeogenesis. Lactate is continuously produced by erythrocytes, and it is also generated by glycolytic skeletal muscle fibers during exercise. However, a significant portion of this lactate is used by aerobic skeletal and cardiac muscles during exercise. Additionally, the overall anabolic processes of the digestive phase switch to a catabolic state during the fasting phase.
FFAs represent the most efficient fuel type in terms of ATP molecules made per carbon of fuel. However, utilization of FFAs competes effectively with glucose utilization in the mitochondria. High FFA levels during the digestive phase would promote a greater magnitude and duration of the glucose surge, thereby contributing to hyperglycemia. Thus most of the FFAs in an average meal are prevented from entering the circulation by their reesterification into TG and packaging into chylomicrons within the intestinal enterocyte. Chylomicrons are secreted, enter lymphatic vessels, and ultimately enter the blood. Once in the general circulation, chylomicrons convey the FFAs (as TG) to the adipose tissue where they are released from chylomicronassociated TG through lipolysis, imported by adipocytes, and reesterified as intracellular TG for storage (discussed in detail later).
During the digestive phase, hepatocytes, skeletal myocytes, and adipocytes function largely independently of each other. In contrast the actions of these three cell types become highly integrated during the fasting phase to maintain adequate blood glucose levels while providing alternative energy substrates for each cell type (see
Fig.
39.3B
Table 39.1
As stated earlier, cells without mitochondria (e.g., erythrocytes) and cells of the CNS require glucose for ATP production during all metabolic phases, and thus the body must maintain blood glucose above 60 mg/dL even days or weeks after the last ingestion of food (an exception to this rule is that the brain can use KBs [discussed later] during a prolonged fasting phase). Two general processes contribute to maintenance of blood glucose during the fasting phase: hepatic glucose production and glucose sparing. Hepatic glucose production is in turn based on two metabolic pathways. The first is the rapid catabolic process of glycogenolysis (pathway 9 in
Fig. 39.3B ). Hepatocytes express the enzyme glucose-6-phosphatase (G6Pase) (pathway 11 in
Fig. 39.3B ), allowing them to convert G6P back to glucose, which can then exit the cell through a bidirectional GLUT transporter. Release of glucose derived from glycogenolysis is relatively short
Source of blood
DietaryGluconeogenesis0 Breakfast 12.00 24.00Glycogenolysis •Fig. 39.4 Relativecontributionsofthethreesourcesofbloodglucoserelativetomealsandtimeofday.Theinsetboxstressesreplacementofglycogenolysiswithgluconeogenesisduringthefastingphase(i.e.,sleep).(AdaptedfromBaynesJW,DominiczakJH[eds].Medical Biochemistry. 3rded.Philadelphia:Mosby/Elsevier;2009.) lived because the liver glycogen supply becomes exhausted by about 8 hours. The second metabolic contribution to hepatic glucose production during the fasting phase is the gradual pathway of gluconeogenesis (pathway 10 in
Fig.
39.3B ). The onset of gluconeogenesis during fasting is slower than glycogenolysis, but gluconeogenesis continues essentially nonstop throughout a fasting phase (
Fig. 39.4 ). Gluconeogenesis requires precursors, especially lactate, “gluconeogenic” AAs, and glycerol. How are these precursors supplied during the fasting phase? Lactate is continually produced by erythrocytes. Lactate is also produced by glycolytic skeletal muscle fibers during exercise (exercise tends to occur more frequently during the interdigestive and fasting phases as opposed to “on a full stomach”), although much of this lactate is utilized by aerobic skeletal muscle and cardiac muscle during exercise. But additionally the overall anabolism of the digestive phase switches over to a general catabolism during the fasting phase (see
Fig.