Chapter 2 The Fed or Absorptive State Human Biochemistry During a meal, we ingest carbohydrates, lipids, and proteins, which are subsequently digested and absorbed. Major fates of fuels in the fed state Fate of Carbohydrates : After a Fate of Proteins : Fate of Fats : meal, glucose is oxidized by In cells, the amino acids are Triacylglycerols are digested to fatty various tissues for energy, converted to proteins or used to acids and 2-monoacylglycerols, enters biosynthetic pathways, make various nitrogen-containing which are resynthesized into and is stored as glycogen and compounds such as triacylglycerols in intestinal triacylglycerols, mainly in the neurotransmitters and heme. The epithelial cells, packaged in liver and muscles. carbon skeleton may also be oxidized chylomicrons and secreted by way of for energy directly, or be converted to the lymph into the blood. The fatty glucose. acids of the chylomicron triacylglycerols are stored mainly as triacylglycerols in adipose cells. They are subsequently oxidized for energy or used in biosynthetic pathways, such as synthesis of membrane lipids. NAFLD (non-alcoholic fatty liver disease) is defined as the accumulation of fat in liver cells, known as fatty liver or hepatic steatosis, in the absence of excessive alcohol consumption (the global prevalence of NAFLD: 25.2%) Dis Model Mech. 2013;6(4):905-14 Hepatology. 2016;64(1):73-84 The fed state The circled numbers indicate the approximate order in which the process occur. TG,triacylglycerols; FA,fatty acid; AA,amino acid; RBC,red blood cell; VLDL,very low- density lipoprotein; I,insulin; CHO,carbohydrate; acetyl CoA,acetyl coenzyme A; ATP,adenosine triphosphate; TCA,tricarbpxylic acid; +,stimulated by. • Monosaccharides produced by digestion and dietary monosaccharides are absorbed by the intestinal epithelial cells and released into the hepatic portal vein, which carries them to the liver. • The triacylglycerols are packaged with proteins, phospholipids, cholesterol, and other compounds into the lipoprotein complexes known as chylomicrons, which are secreted into the lymph and ultimately enter the bloodstream (see circle 2). • Dietary proteins are cleaved to amino acids by enzymes known as proteases (circle 3), which cleave the peptide bond between amino acids. The amino acids derived from dietary proteins travel from the intestine to the liver in the hepatic portal vein (see circle 3). • After a typical high-carbohydrate meal, the pancreas is stimulated to release the hormone insulin, and release of the hormone glucagon is inhibited (see circle 4). • The liver extracts a portion of this glucose from the blood. In the liver, insulin promotes the uptake of glucose by increasing its use as a fuel and its storage as glycogen and triacylglycerols (see circles 5, 6, and 7). Oxidation of fuels in exercising skeletal muscle • Exercising skeletal muscles can use glucose from the blood or from their own glycogen stores, converting glucose to lactate through glycolysis or oxidizing it completely to CO2 and H2O. • Muscle also uses other fuels from the blood such as fatty acids. • After a meal, glucose is used by muscle to replenish the glycogen stores that were depleted during exercise. Glucose is transported into muscle cells and converted to glycogen by processes that are stimulated by insulin. Exercising muscle uses more energy than resting muscle, and therefore fuel use is increased to supply more adenosine triphosphate (ATP). Acetyl CoA,acetyl coenzyme A; TCA,tricarboxylic acid..