Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online

Structure & Reactivity in Chemistry

Metabolic Pathways

Czech translation  from Valeria Aleksandrova

Russian translation of this page by Oleg Segal

MP2. An Overview of Metabolic Pathways - Anabolism

Henry Jakubowski

Anabolism:   Anabolic reactions are those that lead to the synthesis of biomolecules.  In contrast to the catabolic reactions just discussed (glycolysis, TCA cycle and electron transport/oxidative phosphorylation) which lead to the oxidative degradation of carbohydrates and fatty acids and energy release, anabolic reactions lead to the synthesis of more complex biomolecules including biopolymers (glycogen, proteins, nucleic acids) and complex lipids.  Many biosynthetic reactions, including those for fatty acid synthesis, are reductive and hence require reducing agents.  Reductive biosynthesis and complex polymer formation require energy input, usually in the form of ATP whose exergonic cleavage is coupled to endergonic biosynthesis.

 

Cells have evolved interesting mechanism so as not to have oxidative degradation reactions (which release energy) proceed at the same time and in the same cell as reductive biosynthesis (which requires energy input).  Consider this scenario.  You dive into a liver cell and find palmitic acid, a 16C fatty acid.  From where did it come?  Was it just synthesized by the liver cell or did it just enter the cell from a distant location such as adipocytes (fat cells).  Should it be oxidized, which should happen if there is a demand for energy production by the cell, or should the liver cell export it, perhaps to adipocytes, which might happen if there is an excess of energy storage molecules?  Cells have devised many ways to distinguish these opposing needs.  One is by using a slightly different pool of redox reagents for anabolic and catabolic reactions.  Oxidative degradation reactions typically use the redox pair NAD+/NADH (or FAD/FADH2) while reductive biosynthesis often uses phosphorylated variants of NAD+, NADP+/NADPH. In addition, cells often carry out competing reactions in different cellular compartments.  Fatty acid oxidation of our example molecule (palmitic acid) occurs in the mitochondrial matrix, while reductive fatty acid synthesis occurs in the cytoplasm of the cell.  Fatty acids entering the cell destined for oxidative degradation are transported into the mitochondria by the carnitine transport system.  This transport system is inhibited under conditions when fatty acid synthesis is favored.  We will discuss the regulation of metabolic pathways in a subsequent section.  One of the main methods, as we will see, is to activate or inhibit key enzymes in the pathways under a given set of cellular conditions. The key enzyme in fatty acid synthesis, acetyl-CoA carboxylase, is inhibited when cellular conditions require fatty acid oxidation.

 

The following examples give short descriptions of anabolic pathways.  Compare them to the catabolic pathways from the previous section.

Figure:  Gluconeogenesis

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Now its time to see how the various pathways fit together to form an integrated set of pathways. 

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