Metabolic loops

It is often not possible to state at what point in a metabolic loop biosynthesis has been completed and biodegradation begins. An end product X that serves one need of a cell may be a precursor to another cell component Y which is then degraded to complete the loop. The reactions that convert X to Y can be regarded as either biosynthetic (for Y) or catabolic (for X). 

Outline the pathway for biosynthesis of L-leucine from glucose and NH4+ in autotrophic organisms. In addition, outline the pathways for degradation of leucine to C02, water, and NH4+ in the human body. For this overall pathway or "metabolic loop," mark the locations (one or more) at which each of the following processes occurs. 

An initially surprising conclusion drawn from the studies of Schoenheimer and Rittenberg was that proteins within cells are in a continuous steady state of synthesis and degradation. The initial biosynthesis, the processing, oxidative and hydrolytic degradative reactions of peptides, and further catabolism of amino acids all combine to form a series of metabolic loops as discussed in Chapter 17 and dealt with further in Chapters 12 and 29. Within cells some proteins are degraded much more rapidly than others, an important aspect of metabolic control. This is accomplished with the aid of the ubiquitin system (Box 10-C) and proteasomes (Box 7-A).107 Proteins secreted into extracellular fluids often undergo more rapid turnover than do those that remain within cells. 

HDL is synthesized in the liver and is secreted as a phospholipid/apoprotein disk. During transit in the blood, HDL acts as a sink for cholesterol. Hepatocytes have receptors that bind cholesterol-rich HDL particles, thus completing a cycle of transport of cholesterol from the liver to the periphery and back again to the liver. The latter half of this metabolic loop is called reverse cholesterol transport. 

In primates, iron, metabolism is highly efficient 13,14, 15,16,17) Little of the metal is absorbed no specific mechanism exists for its elimination. Because it cannot be effectively cleared, the introduction of excess iron 18, 19, 20) into this closed metabolic loop leads to chronic overload and ultimately to peroxidative tissue damage. For example, patients with severe refractory anemia, such as Cooley s anemia ( -thalassemia major), require chronic transfusions, which increase their body iron by 200-250 mg with each unit of blood administered. Unless these individuals receive chelation therapy, they frequently die in their second or third decade from complications associated with iron overload. 

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