Metabolism of amino acids - exercise - Vladimíra Kvasnicová.
Regulation of metabolism on the cellular level Vladimíra Kvasnicová.
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Transcript of Regulation of metabolism on the cellular level Vladimíra Kvasnicová.
![Page 1: Regulation of metabolism on the cellular level Vladimíra Kvasnicová.](https://reader036.fdocuments.net/reader036/viewer/2022082510/5a4d1b0e7f8b9ab05998d18c/html5/thumbnails/1.jpg)
Regulation of metabolism on the
cellular levelVladimíra Kvasnicová
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General Principles of Regulation
• catabolic / anabolic processes• last step of each regulation mechanism:
change of a concentration of an active enzyme (= regulatory or key enzyme)
• regulatory enzymes often allosteric enzymes catalyze higly exergonic reactions
(irreverzible) low concentration within a cell
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I. Regulation on the organism level
1. signal transmission among cells(signal substances)
2. signal transsduction through the cell membrane
3. influence of enzyme activity: induction of a gene expression interconversion of existing enzymes
(phosphorylation / dephosphorylation)
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II. Regulation on the cell level
1. compartmentalization of mtb pathways2. change of enzyme concentration
(on the level of synthesis of new enzyme )
3. change of enzyme activity(an existing enzyme is activated or inactivated)
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1. Compartmentalization of mtb patways
• transport processes between compartments
• various enzyme distribution• various distribution of substrates and
products ( transport)• transport of coenzymes• subsequent processes are close to each
other
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Compartmentalization of mtb pathways
The figure is found at http://fig.cox.miami.edu/~cmallery/150/proceuc/c7x7metazoan.jpg (May 2007)
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Cytoplasm• glycolysis• gluconeogenesis (from oxaloacetate or glycerol)• metabolism of glycogen• pentose cycle• synthesis of fatty acids• synthesis of nonessential amino acids• transamination reactions • synthesis of urea (a part; only in the liver!)• synthesis of heme (a part)• metabolism of purine and pyrimidine
nucleotides
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Mitochondrion
• pyruvate dehydrogenase complex (PDH)• initiation of gluconeogenesis -oxidation of fatty acids• synthesis of ketone bodies (only in the liver!) • oxidation deamination of glutamate • transamination reactions• citrate cycle• respiratory chain (inner mitochondrial membrane)• aerobic phosphorylation (inner mitoch.
membrane) • synthesis of heme (a part)• synthesis of urea (a part)
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Endoplasmic Reticulum
Smooth ER• synthesis of triacylglycerols and phospholipids• elongation and desaturation of fatty acids• synthesis of steroids• biotransformation of xenobiotics• glucose-6-phosphatase
Rough ER• proteosynthesis
(translation and posttranslational modifications)
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Golgi Apparatus
• posttranslational modification of proteins• protein sorting • export of proteins (formation of vesicules)
Ribosomes • proteosynthesis
Nucleus• replication and transcription of DNA• synthesis of RNA
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Lysosomes
• hydrolysis of proteins, saccharides, lipids and nucleic acids
Peroxisomes
• oxidative reactions involving O2
• use of hydrogen peroxide• degradation of long chain FA (from C20)
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2. Synthesis of new enzyme molecules:
• induction by substrate or repression by product(on the level of transcription)
examples:xenobiotics induction of cyt P450heme repression of delta-aminolevulate
synthase
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3. Change of activity of an existing enzyme
a) in relation to an enzyme kinetics concentration of substrates ( Km) availability of coenzymes consumption of products pH changes substrate specificity - different Km
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b) activation or inactivation of the enzyme• covalent modification of the enzymes
interconversion: phosphorylation/dephosphorylation) cleavage of an precursore (proenzyme, zymogen)
• modulation of activity by modulators (ligands): feed back inhibition cross regulation feed forward activation
3. Change of activity of an existing enzyme
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Phosphorylation / dephosphorylation
• some enzymes are active in a phosphorylated form, some are inactive
• phosphorylation:protein kinasesmacroergic phosphate as a donor of the
phosphate (ATP!)
• dephosphorylationprotein phosphatase inorganic phosphate is the product!
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The figure is found at: http://stallion.abac.peachnet.edu/sm/kmccrae/BIOL2050/Ch1-13/JpegArt1-13/05jpeg/05_jpeg_HTML/index.htm (December 2006)
Reversible covalent modification:
A)• phosphorylation by a protein kinase• dephosphorylation by a protein phosphatase
B)• phosphorylated enzyme is either active or inactive (different enzymes are influenced differently)
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Modulators of enzyme activity(activators, inhibitors)
• isosteric modulation: competitive inhibition
• allosteric modulation:change of Km or Vmax
T-form (less active) or R-form (more active)
• important modulators: ATP / ADP