METABOLIC PATHWAYS ALLOWS CELLS TO USE METABOLITES TO THEIR FULL POTENTIAL.

113
METABOLIC PATHWAYS ALLOWS CELLS TO USE METABOLITES TO THEIR FULL POTENTIAL

Transcript of METABOLIC PATHWAYS ALLOWS CELLS TO USE METABOLITES TO THEIR FULL POTENTIAL.

Page 1: METABOLIC PATHWAYS ALLOWS CELLS TO USE METABOLITES TO THEIR FULL POTENTIAL.

METABOLIC PATHWAYS

ALLOWS CELLS TO USE METABOLITES TO THEIR FULL

POTENTIAL

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METABOLISM

THE SUM OF ALL CELLULAR REACTIONS

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TYPES OF METABOLIC REACTIONS

ANABOLIC VS CATABOLIC

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CATABOLISM

AEROBIC VS ANAEROBIC

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COUPLING AGENTS

ATP

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ATP STRUCTURE

• ADENINE

• RIBOSE

• THREE PHOSPHATE GROUPS

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THE IMPORTANCE OF HIGH ENERGY BONDS

• THIRD PHOSPHATE BOND

• UNSTABLE

• HYDROLYSIS IS EXERGONINC

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ENERGY METABOLISM

OXIDATION VS REDUCTION

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BIOLOGICAL OXIDATION

• REMOVAL OF ELECTIONS IN INORGANIC MOLECULES

• REMOVAL OF HYDROGENS IN ORGANIC MOLECULES

• DEHYDROGENASES

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BIOLOGICAL REDUCTIONS

• ADDITIONS OF ELECTRONS IN INORGANIC

• ADDITIONS OF HYDROGENS IN ORGANIC

• OXIDATION AND REDUCTION MUST OCCUR SIMULTANEOUSLY

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COUPLING AGENTS

COENZYMES

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SUBSTRATES FOR OXIDATION

• INORGANIC COMPOUNDS (REDUCED IRON, SULFUR OR NITROGEN)

• HEXOSES (FRUCTOSE, GLUCOSE, LACTOSE)

• POLYSACCHARIDES

• PROTEINS

• FATS

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GLUCOSE

• HEXOSE• MAIN SUGAR IN

VERTEBRATES• SUGAR RELEASED FROM

STARCH IN PLANTS• CONSTITUENT OF

SUCROSE • BEGINNING POINT FOR

EMBDEN MYERHOFF, ENTNER DUODOROFF, PENTOSE PHOSPHATE PATHWAYS

                                                   

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THE IMPORTANCE OF ELECTRON ACCEPTORS

• OXYGEN

• OTHER INORGANIC MOLECULES

• ORGANIC MOLECULES

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AEROBIC RESPIRATION VS FERMENTATION

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AEROBIC RESPIRATION

• NEED ELECTRON ACCEPTOR FOR OXIDATIONS TO OCCUR

• MOST USE OXYGEN

• ACCESS TO FULL ENERGY OF GLUCOSE REQUIRES OXIDATION

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FERMENTATION

• MOST ORGANISMS CAN EXTRACT ENERGY BY EMBDEN MYERHOFF PATHWAY/GLYCOLYSIS

• DOES NOT REQUIRE OXYGEN• ELECTRONS ARE GIVEN BACK TO AN

ORGANIC MOLECULE THAT IS PYRUVATE OR A DERIVATIVE OF PYRUVATE

• LACTATE, ALCOHOL, ACIDS, ETC

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ANAEROBIC RESPIRATION

• USES FINAL INORGANIC ELECTRON ACCEPTOR OTHER THAN ATMOSPHERIC OXYGEN

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CLASSIFICATION OF ORGANISMS BY THEIR USE OF OXYGEN

• STRICT OR OBLIGATE AEROBES

• STRICT OR OBLIGATE ANAEROBES

• FACULATIVE ANAEROBES

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EMBDEN - MEYERHOFF PATHWAY

GLYCOLYSIS

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EMBDEN-MEYERHOFF

• TEN STEP PATHWAY

• FOUND IN BOTH AEROBIC AND ANAEROBIC ORGANSIMS

• PYRUVATE IS THE END PRODUCT

• CAN BE REDUCED THROUGH FERMENTATION

• OR OXIDIZED FURTHER

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PRODUCTS OF EMBDEN MEYERHOFF

• NADH

• ATP

• PYRUVATE

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PHASES OF THE EMBDEN MEYERHOFF PATHWAY

• PREPRATORY AND CLEAVAGE– STEPS 1-5

• OXIDATIVE – STEPS 6 & 7

• ATP GENERATING PHASE– STEPS 8-10

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PREPARATION AND CLEAVAGE

• FRUCTOSE 1,6 BISPHOSPHATE

• TWO TERMINAL PHOSPHATE GROUPS

• DHAP AND GLYCERALDEHYDE 3 PHOSPHATE

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DHAP AND GLYCERALDEHYDE 3 PHOSPHATE

• DHAP = KETOSE

• GLYCERALDEHYDE 3 PHOSPHATE = ALDOSE

• ONLY GLYCERALDEHYDE 3 PHOSPHATE OXIDIZED

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OXIDATION AND ATP GENERATION

• NEGATIVE ENERGY YIELD SO FAR

• ATP PRODUCTION LINKED TO OXIDATION

• GLYCERALDEHYDE 3 DEHYDROGENASE

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PYRUVATE & ATP FORMATION

• ISOMERIZATION REACTION TO INCREASE AMOUNT OF FREE ENERGY

• 3 PHOSPHOGLCERAATE TO 2PHOSPHOGLYCERATE TO PHOSPHENOLPYRUVATE

• PHOSPHOENOLPYRUVATE TO PYRUVATE

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IMPORTANCE OF PYRUVATE

• BRANCHING POINT

• FATE DEPENDS ON ORGANISM AND OXYGEN

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CATABOLISM OF GLUCOSE BY CELLULAR RESPIRATION

ENERGY RELEASE IS EXACTLY THE SAME AS WHEN SUGAR IS

THROWN ONTO A FIRE

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BURNING GLUCOSE IN OXYGEN RELEASES 686,00

CALORIES PER MOLE

CELLS WILL NOT CAPTURE ALL THIS ENERGY

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THE CATABOLISM OF GLUCOSE

• GLYCOLYSIS—EMBDEN MERYEHOFF PATHWAY

• KREBS CYCLE—TCA CYCLE

• ELECTRON TRANSPORT

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STEP ONE OF GLYCOLYSIS

• SUBSTRATE PHOSPHORYLATION OF GLUCOSE

• CONVERSION TO GLUCOSE 6 PHOSPHATE

• GLUCOSE TRAPPING

• HEXOKINASE IS THE ENZYME USED IN EUKARYOTES

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HORMONAL REGULATION

• MAMMALS REGULATE THIS PHOSPHORYLATION WITH THE HORMONE INSULIN

• THERE ARE MANY HORMONES THAT HELP REGULATE SUGAR METABOLISM

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STEP TWO OF GLYCOLYSIS

• GLUCOSE 6 PHOSPHATE IS REARRANGED INTO FRUCTOSE 6 PHOSPHATE

• PHOSPHOFRUCTOKINASE IS THE ENZYME USED

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STEP THREE OF GLYCOLYSIS

• SUBSTRATE PHOSPHORYLATION OF FRUCTOSE 6 PHOSPHATE TO FORM FRUCTOSE 1, 6 DIPHOSPHATE

• CAN ALSO BE CALLED FRUCTOSE 1,6 BISPHOSPHATE

• PHOSPHOFRUCTOKINASE IS THE ENZYME USED

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IMPORTANCE OF PHOSPHOFRUCTOKINASE

• EXTENSIVELY STUDIED ENZYME

• KEY REGULATOR OF GLYCOLYTIC PATHWAY

• ACTIVITES STIMULATED BY FRUCTOSE 6 PHOSPHATE, AMP AND ADP

• ACTIVITIES INHIBITED BY ATP AND CITRATE

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PHOSPHOFRUCTOKINASE ALLOWS THE CELL TO

BALANCE THE RATES OF GLYCOLYSIS AND THE

KREBS CYCLE

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STEP FOUR OF GLYCOLYSIS

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STEP FIVE OF GLYCOLYSIS

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NO ENERGY HAS BEEN PRODUCED

• IN FACT WE HAVE INVESTED TWO ATPs

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STEP SIX OF GLYCOLYSIS

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STEP SEVEN OF GLYCOLYSIS

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STEP EIGHT OF GLYCOLYSIS

• THIS PRIMES THE GLUCOSE FOR ATP PRODUCTION

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STEP NINE OF GLYCOLYSIS

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STEP TEN OF GLYCOLYSIS

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FOUR ATP MOLECULES WILL BE HARVESTED IN THIS PORTION OF

THE PATHWAY

• TWO ATPs INVESTED EARLIER MUST BE PAID BACK

• THE NET YIELD OF GLYCOLYSIS IS 2 ATPs

• TWO NADHs

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AEROBIC PATHWAYS

• TCA CYCLE/KREBS CYCLE

• ELECTRON TRANSPORT SYSTEM– PRODUCE CARBON DIOXIDE

• WATER

• ENERGY– STORED AS ATP

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KREBS CYCLE

TCA CYCLE

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PREPRATORY RX

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CITRIC ACID AS A REGULATOR OF PHOSPHOFRUCTOKINASE

ACTIVITY

• CITRIC ACID IS AN INHIBITOR OF PHOSPHOFRUCTOKINASE

• PREVENTS GLYCOLYSIS FROM OCCURRING WHEN IT IS NOT NECESSARY

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CITRATE IS A TERTIARY ALCOHOL

• MUST BE CONVERTED TO A SECONDARY ALCOHOL

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ELECTRON TRANSPORT SYSTEM

• GLYCOLYSIS = 2 ATPs

• TCA = 2 ATPs

• MOST OF ATPs PRODUCED BY ETS

• SERIES OF ELECTRON CARRIERS

• REDOX REACTIONS

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ELECTRON TRANSPORT SYSTEM

• FROM MORE NEGATIVE REDUCTION POTENTIALS TO MORE POSITIVE POTENTIALS

• DIFFERENCE BETWEEN NADH AND OXYGEN IS ABOUT 1.14 VOLTS

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SITES OF ATP SYNTHESIS

• BETWEEN NADH AND COENZYME Q

• BETWEEN CYTOCHROME B AND C1

• BETWEEN CYTOCHROME A AND OXYGEN

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ELECTRON TRANSPORT SYSTEM

• ALLOWS SMALL RELEASES OF ENERGY IN SMALL STEPS

• ESTABLISHES PROTON AND ELECTRICAL GRADIENT

• FOUND IN INNER MITOCHONDRIAL MEMBRANE• FOUR COMPLEXES OF CARRIERS• CYTOCHROME C AND COENZYME Q CONNECT

COMPLEXES

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OXIDATIVE PHOSPHORYLATION

• AS MANY AS THREE ATPs FOR EACH TWO ELECTRONS FROM NADH TO OXYGEN

• AS MANY AS TWO ATPs FOR EACH TWO ELECTRONS FROM FADH2 TO OXYGEN

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BACTERIAL ELECTRON TRANSPORT SYSTEMS

• SOME RESEMBLE MITOCHONDRIAL CHAINS

• MANY ARE VERY DIFFERENT

• VARIOUS TYPES OF CYTOCHROMES

• SOME HIGHLY BRANCHED

• MAY BE SHORTER

• HAVE LESS ATP PRODUCTION

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OXIDATIVE PHOSPHORYLATION

• CHEMIOSMOSIS

• CONFORMATIONAL CHANGE HYPOTHESIS

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CHEMIOSMOSIS

• PROTONS MOVE INTO INTERMEMBRANAL SPACE

• CAUSES PROTON MOTIVE FORCE• GRADIENT OF PROTONS• MEMBRANE POTENTIAL DUE TO

UNEVEN DISTRIBUTION OF CHARGES• ATPs MADE AS H+ DIFFUSE BACK

INTO MATRIX

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OTHER USES OF PROTON MOTIVE FORCE

• TRANSPORT ACROSS MEMBRANES

• ROTATION OF BACTERIAL FLAGELLA

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CONFORMATIONAL CHANGE HYPOTHESIS

• ENERGY RELEASED CAUSES CHANGES IN THE SHAPE OF ATPase ENZYME

• CHANGES DO ACTUALLY OCCUR DURING ELECTRON TRANSPORT

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INHIBITORS OF ELECTRON TRANSPORT

• BLOCK ELECTRON TRANSPORT

• UNCOUPLE ATPase AND ELECTRON TRANSPORT

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BLOCKERS

• PERICIDIN -- COMPETES WITH COENZYME Q FOR ELECTRONS

• ANTIMYCIN A -- BLOCKS ELECTRON TRANSPORT BETWEEN B AND C

• CYANIDE & AZIDE -- STOP TRANSFER BETWEEN CYTOCHROME A AND OXYGEN

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UNCOUPLERS

• DO NOT AFFECT ELECTRON TRANSPORT

• DISCONNECT OXIDATIVE PHOSPHORYLATION FROM ELECTRON TRANSPORT

• ENERGY IS RELEASED AS HEAT

• DINTITOPHENOL & VALINOMYCIN

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ATP YIELDS

GLYCOLYSIS & AEROBIC RESPIRATION

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GLYCOLYSIS

• NET YIELD OF 2 ATPs

• TWO NADHs PRODUCE SIX ATPs

• TOTAL OF EIGHT ATPs

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PREPARATORY REACTION

• 2 NADHs FOR A YIELD OF 6 ATPs

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TCA CYCLE

• 2 ATPs

• 6 NADHs FOR 18 ATPs

• 2 FADH2s FOR 4 ATPs

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ANAEROBIC PATHWAYS

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LACTATE FERMENTATION

• DIRECT TRANSFER FROM NADH TO PYRUVATE

• LACTATE DEHYDROGENASE

• MAJOR PATHWAY IN MANY ANAEROBIC BACTERIA

• MUSCLES

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ETHANOL FERMENTATION

• NADH AND ACETALDEHYDE (A DERIVATIVE OF PYRUVATE)

• TWO STEP SEQUENCE• DECARBOXYLATION--

PYRUVATE DECARBOXYLASE

• ACETALDEHYDE REDUCTION -- ALCOHOL DEHYDROGENASE

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TYPES OF FERMENTATIONS

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ALCOHOLIC FERMENTATION

• FUNGI

• ALGAE

• BACTERIA

• PROTOZOA

• SUGARS --------> ALCOHOL

• ALCOHOL DEHYDROGENASE

• NADH DONOR

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LACTIC ACID FERMENTATION

• REDUCTION OF PYRUVATE TO LACTATE• MORE COMMON THAN ALCOHOL

FERMENTATION• BACTERIA• ALGAE• WATER MOLDS• PROTOZOA• ANIMAL MUSCLE CELLS

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HOMOLACTIC ACID FERMENTERS

• LACTATE DEHYDROGENASE

• USE GLYCOLYTIC PATHWAY

• TWO KINDS OF LACTIC ACID FERMENTERS

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HETEROLACTIC FERMENTERS

• MANY PRODUCE LACTATE

• ETHANOL

• VARIETY OF OTHER PRODUCTS

• USES PHOSPHOKETALOSE PATHWAY

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FORMIC ACID FERMENTERS

MIXED ACID FERMENTATION

BUTANEDIOL FERMENTATION

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MIXED ACID FERMENTATION

• ENTEROBACTERIACEAE

• PYRUVATE ---->

• HYDROGEN GAS

• CARBON DIOXIDE

• FORMIC HYDROGENLYASE

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MIXED ACID FERMENTATION

• ETHANOL

• COMPLEX MIXTURE OF ACIDS

• ACETIC

• LACTIC

• SUCCINIC

• FORMIC

• ESCHERICHIA, SALMONELLA & ETC

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ATP GENERATION IN FORMIC ACID

FERMENTATION• SOMETIME GENERATE ATP WILL

REOXIDIZING NADH

• USE ACETYL CO A -------> ACETYL-PHOSPHATE

• DONATES TO ADP

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FERMENTERS OF AMINO ACIDS

• STICKLAND REACTION

• CLOSTRIDIUM SPECIES

• GENERATE AMMONIA, HYDROGEN SULFIDE, FATTY ACIDS AND AMINES

• PUTREFACTION ODORS

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ANAEROBIC RESPIRATION

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ANAEROBIC RESPIRATION

• ELECTRON TRANSPORT SYSTEMS DONATE ELECTRONS TO INORGANIC MOLECULES OTHER THAN OXYGEN

• NITRATE

• SULFATE

• CARBON DIOXIDE

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NITRATE

• NO3 + 2 e- + 2 H+ -------> NO2 + H2O

• NITRATE IS THE ELECTRON ACCEPTOR

• NITRATE REDUCTASE REPLACES CYTOCHROME OXIDASE

• NOT EFFECTIVE

• PRODUCT TOXIC

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DENITRIFICATION

• REDUCED ALL THE WAY TO N2

• ACCEPTS FIVE ELECTRONS

• IS NONTOXIC

• 2 NO3 + 10 e- + 12 H+ ------> N2 + 6 H2O

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THE PENTOSE-PHOSPHATE PATHWAY

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THE PENTOSE PHOSPHATE PATHWAY

• HEXOSE MONOPHOSPHATE PATHWAY

• CAN OPERATE AT SAME TIME AS EMBDEN-MEYERHOF

• AEROBIC OR ANAEROBIC• PROVIDES THREE TO SEVEN

CARBON SUGARS PHOSPHATE• NADPH IS ALSO PRODUCED

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END PRODUCTS

• FRUCTOSE 6 PHOSPHATE

• GLYCERALDEHYDE 3 PHOSPHATE

• THREE CARBON DIOXIDE MOLECULES

• 6 NADPHs

• INTERMEDIATES FOR ANABOLIC REACTIONS

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P GLUCOSE 6 - PHOSPHATE

`

NADPH

6-PHOSPHOGLUCONATE

NADPH

RIBULOSE 5 - PHOSPHATE

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END PRODUCTS

ERYTHROSE 4 PHOSPHATE XYLOSE 5 PHOSPHATE

GLYCERALDEHYDE 3 PHOSPHATE FRUCTOSE 6 PHOSPHATE

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IMPORTANCE OF PENTOSE PHOSPHATE PATHWAY

• MAKES ATP• NADPH ACTS AS SOURCE OF

ELECTRONS FOR BIOSYNTHESIS• PRODUCES FOUR AND FIVE CARBON

SUGARS WHICH CAN BE USED • PRODUCES HEXOSE SUGARS FOR

MICROBES GROWN ON PENTOSE CARBON SOURCE

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ENTNER DOUDOROFF PATHWAY

• STARTS WITH GLUCOSE 6 PHOSPHATE

• DEHYDRATION FORMS KDPG

• END PRODUCTS ARE PGAL AND PYRUVATE

• PGAL CAN ENTER LOWER PART OF GLYCOLYSIS

• ONE ATP, ONE NADPH AND ONE NAD

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BETA OXIDATION

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BETA OXIDATION

• REMOVAL OF TWO CARBON GROUPS

• TO FORM ACETYL CoA– MAY ENTER KREBS CYCLE

• NADH AND FADH2 IS FORMED

                               

                                                                                                                 

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PROTEIN METABOLISM

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AMINO ACID BIOSYNTHESIS

• ADD AMINE GROUP TO KETO ACID

• SIMPLE ONE STEP TRANSMINATION REACTION– GLUTAMATE AND ASPARTATE ARE

EXAMPLES

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CATABOLISM OF AMINO ACIDS

• REMOVAL OF AMINE GROUP FROM AMINO ACID

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CATABOLISM OF PROTEINS AND AMINO ACIDS

• PATHOGENIC, FOOD SPOILERS, SOIL MICROBES

• PROTEASE ENZYMES• DEAMINATION• TRANSAMINATION• ALPHA KETO ACID ACCEPTOR• AMMONIUM ION MAY MAKE

MEDIUM ALKALINE