Computational functions in biochemical reaction networks
In prior work we demonstrated the implementation of logic gates, sequential computers (universal Turing machines), and parallel computers by means of the kinetics of chemical reaction mechanisms. In the present article we develop this subject further by first investigating the computational properti...
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| Vydáno v: | Biophysical journal Ročník 67; číslo 2; s. 560 |
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| Hlavní autoři: | , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.08.1994
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| ISSN: | 0006-3495 |
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| Abstract | In prior work we demonstrated the implementation of logic gates, sequential computers (universal Turing machines), and parallel computers by means of the kinetics of chemical reaction mechanisms. In the present article we develop this subject further by first investigating the computational properties of several enzymatic (single and multiple) reaction mechanisms: we show their steady states are analogous to either Boolean or fuzzy logic gates. Nearly perfect digital function is obtained only in the regime in which the enzymes are saturated with their substrates. With these enzymatic gates, we construct combinational chemical networks that execute a given truth-table. The dynamic range of a network's output is strongly affected by "input/output matching" conditions among the internal gate elements. We find a simple mechanism, similar to the interconversion of fructose-6-phosphate between its two bisphosphate forms (fructose-1,6-bisphosphate and fructose-2,6-bisphosphate), that functions analogously to an AND gate. When the simple model is supplanted with one in which the enzyme rate laws are derived from experimental data, the steady state of the mechanism functions as an asymmetric fuzzy aggregation operator with properties akin to a fuzzy AND gate. The qualitative behavior of the mechanism does not change when situated within a large model of glycolysis/gluconeogenesis and the TCA cycle. The mechanism, in this case, switches the pathway's mode from glycolysis to gluconeogenesis in response to chemical signals of low blood glucose (cAMP) and abundant fuel for the TCA cycle (acetyl coenzyme A). |
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| AbstractList | In prior work we demonstrated the implementation of logic gates, sequential computers (universal Turing machines), and parallel computers by means of the kinetics of chemical reaction mechanisms. In the present article we develop this subject further by first investigating the computational properties of several enzymatic (single and multiple) reaction mechanisms: we show their steady states are analogous to either Boolean or fuzzy logic gates. Nearly perfect digital function is obtained only in the regime in which the enzymes are saturated with their substrates. With these enzymatic gates, we construct combinational chemical networks that execute a given truth-table. The dynamic range of a network's output is strongly affected by "input/output matching" conditions among the internal gate elements. We find a simple mechanism, similar to the interconversion of fructose-6-phosphate between its two bisphosphate forms (fructose-1,6-bisphosphate and fructose-2,6-bisphosphate), that functions analogously to an AND gate. When the simple model is supplanted with one in which the enzyme rate laws are derived from experimental data, the steady state of the mechanism functions as an asymmetric fuzzy aggregation operator with properties akin to a fuzzy AND gate. The qualitative behavior of the mechanism does not change when situated within a large model of glycolysis/gluconeogenesis and the TCA cycle. The mechanism, in this case, switches the pathway's mode from glycolysis to gluconeogenesis in response to chemical signals of low blood glucose (cAMP) and abundant fuel for the TCA cycle (acetyl coenzyme A).In prior work we demonstrated the implementation of logic gates, sequential computers (universal Turing machines), and parallel computers by means of the kinetics of chemical reaction mechanisms. In the present article we develop this subject further by first investigating the computational properties of several enzymatic (single and multiple) reaction mechanisms: we show their steady states are analogous to either Boolean or fuzzy logic gates. Nearly perfect digital function is obtained only in the regime in which the enzymes are saturated with their substrates. With these enzymatic gates, we construct combinational chemical networks that execute a given truth-table. The dynamic range of a network's output is strongly affected by "input/output matching" conditions among the internal gate elements. We find a simple mechanism, similar to the interconversion of fructose-6-phosphate between its two bisphosphate forms (fructose-1,6-bisphosphate and fructose-2,6-bisphosphate), that functions analogously to an AND gate. When the simple model is supplanted with one in which the enzyme rate laws are derived from experimental data, the steady state of the mechanism functions as an asymmetric fuzzy aggregation operator with properties akin to a fuzzy AND gate. The qualitative behavior of the mechanism does not change when situated within a large model of glycolysis/gluconeogenesis and the TCA cycle. The mechanism, in this case, switches the pathway's mode from glycolysis to gluconeogenesis in response to chemical signals of low blood glucose (cAMP) and abundant fuel for the TCA cycle (acetyl coenzyme A). In prior work we demonstrated the implementation of logic gates, sequential computers (universal Turing machines), and parallel computers by means of the kinetics of chemical reaction mechanisms. In the present article we develop this subject further by first investigating the computational properties of several enzymatic (single and multiple) reaction mechanisms: we show their steady states are analogous to either Boolean or fuzzy logic gates. Nearly perfect digital function is obtained only in the regime in which the enzymes are saturated with their substrates. With these enzymatic gates, we construct combinational chemical networks that execute a given truth-table. The dynamic range of a network's output is strongly affected by "input/output matching" conditions among the internal gate elements. We find a simple mechanism, similar to the interconversion of fructose-6-phosphate between its two bisphosphate forms (fructose-1,6-bisphosphate and fructose-2,6-bisphosphate), that functions analogously to an AND gate. When the simple model is supplanted with one in which the enzyme rate laws are derived from experimental data, the steady state of the mechanism functions as an asymmetric fuzzy aggregation operator with properties akin to a fuzzy AND gate. The qualitative behavior of the mechanism does not change when situated within a large model of glycolysis/gluconeogenesis and the TCA cycle. The mechanism, in this case, switches the pathway's mode from glycolysis to gluconeogenesis in response to chemical signals of low blood glucose (cAMP) and abundant fuel for the TCA cycle (acetyl coenzyme A). |
| Author | Arkin, A Ross, J |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/7948674$$D View this record in MEDLINE/PubMed |
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| References | 11607249 - Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):383-7 2626059 - J Theor Biol. 1989 Apr 20;137(4):423-44 16502 - Am J Physiol. 1977 May;232(5):R164-74 17838251 - Science. 1993 Apr 16;260(5106):335-7 4325748 - Comput Biomed Res. 1971 Apr;4(1):65-106 |
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| SubjectTerms | Biochemistry - methods Citric Acid Cycle Enzymes - metabolism Gluconeogenesis Glycolysis Kinetics Logic Models, Theoretical Substrate Specificity |
| Title | Computational functions in biochemical reaction networks |
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