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    Metabolism

    Dr.Dawelbiet Abdelaal

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    Metabolism is the set of chemical reactions

    that happen in living organisms to maintain

    life. These processes allow organisms togrow and reproduce, maintain their

    structures, and respond to their

    environments. Metabolism is the sum of:

    Catabolism (destruction)

    - Anabolism (construction)

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    Catabolism :is the degradation of nutrients

    (carbohydrates, lipids and proteins) to

    generate energy and starting materials. Anabolism : is the biosynthesis of

    biomolecules from the starting materials.

    Metabolites : substrates , intermediates and

    products of metabolism.

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    The enzymatic reactions of metabolism form a

    network of interconnected chemical reactions, or

    pathways.

    The molecules of the pathway are called

    intermediates because the products of one reaction

    become the substrates of the next.

    Enzymes control the flow of energy through apathway.

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    Coenzym-A

    Performs a vital role by transporting acetyl

    groups from one substrate to anther.

    The key to this action is the reactivethioester bond in the acetyl form of coA.

    The thioester bond is stable enough that it

    can survive inside the cell, but unstable

    enough that acetyl-coA can readily transfer

    the acetyl to anther molcule.

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    Structure of Acetyl CoA

    The structure of Acetyl CoA consists of twoparts.

    1. Acetyl group2. Coenzyme A

    - Beta-mercaptoethylamine

    - Pantothenic acid (not synthesized in man an essential

    nutrient)

    - Phosphate

    - 3', 5'-adenosine diphosphate

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    Structure of acetyl-coA

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    Glycolysis

    Glycolysis takes place in the cytosol of cells.

    Glucose enters the glycolysis pathway byconversion to glucose-6-phosphate.

    Glucose

    10 steps

    Pyruvate

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    Step 1

    The enzyme hexokinase phosphorylates

    (adds a phosphate group to) glucose in the

    cell's cytoplasm. In the process, a phosphate

    group from ATP is transferred to glucose

    producing glucose 6-phosphate.

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    Step 2The enzyme phosphoglucoisomerase converts

    glucose 6-phosphate into its isomer fructose 6-

    phosphate. Isomers have the same molecularformula, but the atoms of each molecule are

    arranged differently.

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    Step 3

    The enzyme phosphofructokinase uses

    another ATP molecule to transfer a

    phosphate group to fructose 6-phosphate to

    form fructose 1, 6-bisphosphate.

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    Step 4The enzyme aldolase splits fructose 1, 6-

    bisphosphate into two sugars that are isomers of

    each other. These two sugars are dihydroxyacetonephosphate and glyceraldehyde phosphate.

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    Step 5The enzyme triose phosphate isomerase rapidlyinter-converts the molecules dihydroxyacetone

    phosphate and glyceraldehyde phosphate.Glyceraldehyde phosphate is removed as soon as itis formed to be used in the next step of glycolysis.- Dihydroxyacetone phosphate (C3H5O3P1) Glyceraldehyde phosphate (C3H5O3P1)

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    Step 6

    The enzyme triose phosphate dehydrogenase serves two functions in this step.

    First the enzyme transfers a hydrogen (H-) from glyceraldehyde phosphate to

    the oxidizing agent nicotinamide adenine dinucleotide (NAD+) to form NADH.

    Next triose phosphate dehydrogenase adds a phosphate (P) from the cytosol tothe oxidized glyceraldehyde phosphate to form 1, 3-diphoshoglyceric acid. This

    occurs for both molecules of glyceraldehyde phosphate produced in step 5.

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    Energy producing phase

    Step 7The enzyme phosphoglycerokinase transfers a P

    from 1,3-diphoshoglyceric acid to a molecule ofADP to form ATP. This happens for each moleculeof 1,3-diphoshoglyceric acid. The process yieldstwo 3-phosphoglyceric acid molecules and twoATP molecules.

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    Step 8The enzyme phosphoglyceromutase relocates the P

    from 3-phosphoglyceric acid from the third

    carbon to the second carbon to form 2-phosphoglyceric acid.

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    Step 9The enzyme enolase removes a molecule of water

    from 2-phosphoglyceric acid to form

    phosphoenolpyruvic acid (PEP). This happens foreach molecule of 2-phosphoglyceric acid.

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    Step 10The enzyme pyruvate kinase transfers a P from

    PEP to ADP to form pyruvic acid and ATP. This

    happens for each molecule of PEP. This reactionyields 2 molecules of pyruvic acid and 2 ATP

    molecules.

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    Regulation 0f glycolysis

    Glycolysis is regulated at three main irreversiblereactions

    (1)Glucose-6-phosphate formation. The entry point of

    glucose is the formation of glucose-6-phosphate.Hexokinase is feedback-inhibited by its product, so thephosphorylation of glucose is inhibited if there is abuildup of glucose-6- phosphate. This regulation reducesthe rate of formation of glucose-6-phosphate.

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    (2)Fructose-6-phosphate fructose-1,6-bisphosphate.Glucose-6-phosphate has other metabolic fates thansimply leading to pyruvate. For example, it can beused to synthesize ribose for DNA and RNA

    nucleotides. The most important regulatory step ofglycolysis is the phosphofructokinase reaction.Phosphofructokinase is regulated by the energycharge of the cellthat is, the fraction of theadenosine nucleotides of the cell that contain high-

    energy bonds

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    (3)Phosphoenol pyruvate pyruvate. The third bigstep in the free-energy diagram is the pyruvate-kinase reaction, where ATP is formed fromphosphoenol pyruvate. ATP inhibits pyruvate

    kinase, similar to the inhibition of PFK. Pyruvatekinase is also inhibited by acetyl-Coenzyme A, theproduct of pyruvate metabolism that enters the TCAcycle. Fatty acids also allosterically inhibit pyruvatekinase, serving as an indicator that alternative

    energy sources are available for the cell.

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    Summary

    In summary, a single glucose molecule in glycolysis

    produces a total of 2 molecules of pyruvic acid, 2 molecules

    of ATP, 2 molecules of NADH and 2 molecules of water.

    Although 2 ATP molecules are used in steps 1-3, 2 ATP

    molecules are generated in step 7 and 2 more in step 10.

    This gives a total of 4 ATP molecules produced. If you

    subtract the 2 ATP molecules used in steps 1-3 from the 4

    generated at the end of step 10, you end up with a net total

    of 2 ATP molecules produced.

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    Anaerobic glycolysis

    The conversion of glucose to lactate in the absenceof oxygen has been termed anaerobic glycolysis.

    Glycolysis provides 2 moles of ATP per mole of

    glucose. The enzyme responsible for conversion of

    pyruvate to lactate is lactate dehydrogenase

    The hydrogen that is produced by the glycolytic

    glyceraldehyde 3-P dehydrogenase reaction isexcreted as lactate.exercising muscle, red bloodcells.