{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

Lecture 8 in Powerpoint format

# It then sets out to quantify the distribution of

This preview shows page 1. Sign up to view the full content.

This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: s out to quantify the distribution of control within a pathway. The degree of control by an enzyme (or group of enzymes) is described quantitatively in the form of flux control coefficients (see next slide). 1 It also can be used to assess the control over the concentrations of the metabolites in a pathway. The distribution of control over metabolite concentrations is described quantitatively in the form of concentration control coefficients. 2 What is a flux control coefficient? A flux control coefficient describes quantitatively how much control a step (or block of steps) has over the flux through a pathway. Flux control coefficients range from -1 to +1 If some perturbation of an enzyme increases its rate by 5%, and the whole pathway by 2%, the enzyme is said to have a flux control coefficient of 2/5, or 0.4. If another perturbation of another enzyme causes its rate to increase by 5%, but the activity of the whole pathway decreases by 2%, the enzyme is said to have a flux control coefficient of -2/5 = -0.4. The sum of all coefficients for a pathway equals 1 (This is called the summation theorem) 0.40 A 0.25 B 0.15 C 0.20 D E Flux Control Coefficients in a Branched Metabolic Pathway Branched For flux A to D For Note that the Summation Theorem holds for branched pathways too Note Applications of Metabolic Control Analysis Control Medical research Medical What What enzymes in a given pathway become disordered in a given disease? • E.g., Altered activity of glycolytic enzymes – implications for pathologies associated with diabetes (retinopathy, neuropathy) pathologies • E.g., hyperthyroidism and impaired oxidative phosphorylation Can Can pharmaceuticals be better designed to normalize metabolic fluxes in disease? metabolic Metabolomics Metabolomics Number of publications per year The field of metabolomics is growing ! Metabolomics: The comprehensive and quantitative analysis of all metabolites in a biological system Avoids exclusion of any metabolites Allows high sample throughput capabilities Attempts to incorporate findings into a broader picture, to improve the understanding of biochemical networks It is a systems biology approach Metabolite: Any organic molecule with a MW < 1000 Da Includes peptides, oligonucleotides, sugars, nucelosides, organic acids, ketones, aldehydes, amines, amino acids, lipids, steroids, and drugs (xenobiotics) Metabolome: a comprehensive term used to describe all the possible metabolites for a biological system (just as genome and proteome refer to all possible genes and proteins) ‘omics’ Genomics 30,000 Genes Genes 106 Proteins +++ Metabolites Proteomics Metabolomics Sample Metabolite List Sample (+)-(-)-Methylsuccinic Acid 2,5-Dihydroxyphenylacetic Acid 2-hydroxy-3-methylbutyric acid 2-Oxoglutaric acid 3-Hydroxy-3-methylglutaric acid 3-Indoxyl Sulfate 5-Hydroxyindole-3-acetic Acid Acetamide Acetic Acid Acetoacetic Acid Acetone Acetyl-L-carnitine Alpha-Glucose Alpha-ketoisocaproic acid Benzoic Acid Betaine Beta-Lactose Citric Acid Creatine Creatinine D(-)Fructose D-(+)-Glyceric Acid D(+)-Xylose Dimethylamine DL-B-Aminoisobutyric Acid DL-Carnitine DL-Citrulline DL-Malic Acid Ethanol Formic Acid Fumaric Acid Gamma-Amino-N-Butyric Acid Gamma-Hydroxybutyric Acid Gentisic Acid Glutaric acid Glycerol Glycine Glycolic Acid Hippuric acid Homovanillic acid Hypoxanthine Imidazole Inositol isovaleric acid L(-) Fucose L-alanine L-asparagine L-aspartic acid L-Histidine L-homocitrulline L-Isol...
View Full Document

{[ snackBarMessage ]}

### What students are saying

• As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

Kiran Temple University Fox School of Business ‘17, Course Hero Intern

• I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

Dana University of Pennsylvania ‘17, Course Hero Intern

• The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

Jill Tulane University ‘16, Course Hero Intern