Extreme pathway analysis of human red blood cell metabolism.
The development of high-throughput technologies and the resulting large-scale data sets have necessitated a systems approach to the analysis of metabolic networks. One way to approach the issue of complex metabolic function is through the calculation and interpretation of extreme pathways. Extreme pathways are a mathematically defined set of generating vectors that describe the conical steady-state solution space for flux distributions through an entire metabolic network. Herein, the extreme pathways of the well-characterized human red blood cell metabolic network were calculated and interpreted in a biochemical and physiological context. These extreme pathways were divided into groups based on such criteria as their cofactor and by-product production, and carbon inputs including those that 1) convert glucose to pyruvate; 2) interchange pyruvate and lactate; 3) produce 2,3-diphosphoglycerate that binds to hemoglobin; 4) convert inosine to pyruvate; 5) induce a change in the total adenosine pool; and 6) dissipate ATP. Additionally, results from a full kinetic model of red blood cell metabolism were predicted based solely on an interpretation of the extreme pathway structure. The extreme pathways for the red blood cell thus give a concise representation of red blood cell metabolism and a way to interpret its metabolic physiology.
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
Sharon J
SJ
Wiback
Bernhard O
BO
Palsson
D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008954:Models, Biological; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D012984:Software
D006454:Hemoglobins; D007773:Lactates; D011773:Pyruvates; D019794:2,3-Diphosphoglycerate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D000241:Adenosine