METABOLIC PATHWAYS ALLOWS CELLS TO USE METABOLITES TO THEIR FULL POTENTIAL

METABOLIC PATHWAYS

ALLOWS CELLS TO USE METABOLITES TO THEIR FULL

POTENTIAL

METABOLISM

THE SUM OF ALL CELLULAR REACTIONS

TYPES OF METABOLIC REACTIONS

ANABOLIC VS CATABOLIC

CATABOLISM

AEROBIC VS ANAEROBIC

COUPLING AGENTS

ATP

ATP STRUCTURE

• ADENINE

• RIBOSE

• THREE PHOSPHATE GROUPS

THE IMPORTANCE OF HIGH ENERGY BONDS

• THIRD PHOSPHATE BOND

• UNSTABLE

• HYDROLYSIS IS EXERGONINC

ENERGY METABOLISM

OXIDATION VS REDUCTION

BIOLOGICAL OXIDATION

• REMOVAL OF ELECTIONS IN INORGANIC MOLECULES

• REMOVAL OF HYDROGENS IN ORGANIC MOLECULES

• DEHYDROGENASES

BIOLOGICAL REDUCTIONS

• ADDITIONS OF ELECTRONS IN INORGANIC

• ADDITIONS OF HYDROGENS IN ORGANIC

• OXIDATION AND REDUCTION MUST OCCUR SIMULTANEOUSLY

COUPLING AGENTS

COENZYMES

SUBSTRATES FOR OXIDATION

• INORGANIC COMPOUNDS (REDUCED IRON, SULFUR OR NITROGEN)

• HEXOSES (FRUCTOSE, GLUCOSE, LACTOSE)

• POLYSACCHARIDES

• PROTEINS

• FATS

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

THE IMPORTANCE OF ELECTRON ACCEPTORS

• OXYGEN

• OTHER INORGANIC MOLECULES

• ORGANIC MOLECULES

AEROBIC RESPIRATION VS FERMENTATION

AEROBIC RESPIRATION

• NEED ELECTRON ACCEPTOR FOR OXIDATIONS TO OCCUR

• MOST USE OXYGEN

• ACCESS TO FULL ENERGY OF GLUCOSE REQUIRES OXIDATION

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

ANAEROBIC RESPIRATION

• USES FINAL INORGANIC ELECTRON ACCEPTOR OTHER THAN ATMOSPHERIC OXYGEN

CLASSIFICATION OF ORGANISMS BY THEIR USE OF OXYGEN

• STRICT OR OBLIGATE AEROBES

• STRICT OR OBLIGATE ANAEROBES

• FACULATIVE ANAEROBES

EMBDEN - MEYERHOFF PATHWAY

GLYCOLYSIS

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

PRODUCTS OF EMBDEN MEYERHOFF

• NADH

• ATP

• PYRUVATE

PHASES OF THE EMBDEN MEYERHOFF PATHWAY

• PREPRATORY AND CLEAVAGE– STEPS 1-5

• OXIDATIVE – STEPS 6 & 7

• ATP GENERATING PHASE– STEPS 8-10

PREPARATION AND CLEAVAGE

• FRUCTOSE 1,6 BISPHOSPHATE

• TWO TERMINAL PHOSPHATE GROUPS

• DHAP AND GLYCERALDEHYDE 3 PHOSPHATE

DHAP AND GLYCERALDEHYDE 3 PHOSPHATE

• DHAP = KETOSE

• GLYCERALDEHYDE 3 PHOSPHATE = ALDOSE

• ONLY GLYCERALDEHYDE 3 PHOSPHATE OXIDIZED

OXIDATION AND ATP GENERATION

• NEGATIVE ENERGY YIELD SO FAR

• ATP PRODUCTION LINKED TO OXIDATION

• GLYCERALDEHYDE 3 DEHYDROGENASE

PYRUVATE & ATP FORMATION

• ISOMERIZATION REACTION TO INCREASE AMOUNT OF FREE ENERGY

• 3 PHOSPHOGLCERAATE TO 2PHOSPHOGLYCERATE TO PHOSPHENOLPYRUVATE

• PHOSPHOENOLPYRUVATE TO PYRUVATE

IMPORTANCE OF PYRUVATE

• BRANCHING POINT

• FATE DEPENDS ON ORGANISM AND OXYGEN

CATABOLISM OF GLUCOSE BY CELLULAR RESPIRATION

ENERGY RELEASE IS EXACTLY THE SAME AS WHEN SUGAR IS

THROWN ONTO A FIRE

BURNING GLUCOSE IN OXYGEN RELEASES 686,00

CALORIES PER MOLE

CELLS WILL NOT CAPTURE ALL THIS ENERGY

THE CATABOLISM OF GLUCOSE

• GLYCOLYSIS—EMBDEN MERYEHOFF PATHWAY

• KREBS CYCLE—TCA CYCLE

• ELECTRON TRANSPORT

STEP ONE OF GLYCOLYSIS

• SUBSTRATE PHOSPHORYLATION OF GLUCOSE

• CONVERSION TO GLUCOSE 6 PHOSPHATE

• GLUCOSE TRAPPING

• HEXOKINASE IS THE ENZYME USED IN EUKARYOTES

HORMONAL REGULATION

• MAMMALS REGULATE THIS PHOSPHORYLATION WITH THE HORMONE INSULIN

• THERE ARE MANY HORMONES THAT HELP REGULATE SUGAR METABOLISM

STEP TWO OF GLYCOLYSIS

• GLUCOSE 6 PHOSPHATE IS REARRANGED INTO FRUCTOSE 6 PHOSPHATE

• PHOSPHOFRUCTOKINASE IS THE ENZYME USED

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

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

PHOSPHOFRUCTOKINASE ALLOWS THE CELL TO

BALANCE THE RATES OF GLYCOLYSIS AND THE

KREBS CYCLE

STEP FOUR OF GLYCOLYSIS

STEP FIVE OF GLYCOLYSIS

NO ENERGY HAS BEEN PRODUCED

• IN FACT WE HAVE INVESTED TWO ATPs

STEP SIX OF GLYCOLYSIS

STEP SEVEN OF GLYCOLYSIS

STEP EIGHT OF GLYCOLYSIS

• THIS PRIMES THE GLUCOSE FOR ATP PRODUCTION

STEP NINE OF GLYCOLYSIS

STEP TEN OF GLYCOLYSIS

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

AEROBIC PATHWAYS

• TCA CYCLE/KREBS CYCLE

• ELECTRON TRANSPORT SYSTEM– PRODUCE CARBON DIOXIDE

• WATER

• ENERGY– STORED AS ATP

KREBS CYCLE

TCA CYCLE

PREPRATORY RX

CITRIC ACID AS A REGULATOR OF PHOSPHOFRUCTOKINASE

ACTIVITY

• CITRIC ACID IS AN INHIBITOR OF PHOSPHOFRUCTOKINASE

• PREVENTS GLYCOLYSIS FROM OCCURRING WHEN IT IS NOT NECESSARY

CITRATE IS A TERTIARY ALCOHOL

• MUST BE CONVERTED TO A SECONDARY ALCOHOL

ELECTRON TRANSPORT SYSTEM

• GLYCOLYSIS = 2 ATPs

• TCA = 2 ATPs

• MOST OF ATPs PRODUCED BY ETS

• SERIES OF ELECTRON CARRIERS

• REDOX REACTIONS

ELECTRON TRANSPORT SYSTEM

• FROM MORE NEGATIVE REDUCTION POTENTIALS TO MORE POSITIVE POTENTIALS

• DIFFERENCE BETWEEN NADH AND OXYGEN IS ABOUT 1.14 VOLTS

SITES OF ATP SYNTHESIS

• BETWEEN NADH AND COENZYME Q

• BETWEEN CYTOCHROME B AND C1

• BETWEEN CYTOCHROME A AND OXYGEN

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

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

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

OXIDATIVE PHOSPHORYLATION

• CHEMIOSMOSIS

• CONFORMATIONAL CHANGE HYPOTHESIS

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

OTHER USES OF PROTON MOTIVE FORCE

• TRANSPORT ACROSS MEMBRANES

• ROTATION OF BACTERIAL FLAGELLA

CONFORMATIONAL CHANGE HYPOTHESIS

• ENERGY RELEASED CAUSES CHANGES IN THE SHAPE OF ATPase ENZYME

• CHANGES DO ACTUALLY OCCUR DURING ELECTRON TRANSPORT

INHIBITORS OF ELECTRON TRANSPORT

• BLOCK ELECTRON TRANSPORT

• UNCOUPLE ATPase AND ELECTRON TRANSPORT

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

UNCOUPLERS

• DO NOT AFFECT ELECTRON TRANSPORT

• DISCONNECT OXIDATIVE PHOSPHORYLATION FROM ELECTRON TRANSPORT

• ENERGY IS RELEASED AS HEAT

• DINTITOPHENOL & VALINOMYCIN

ATP YIELDS

GLYCOLYSIS & AEROBIC RESPIRATION

GLYCOLYSIS

• NET YIELD OF 2 ATPs

• TWO NADHs PRODUCE SIX ATPs

• TOTAL OF EIGHT ATPs

PREPARATORY REACTION

• 2 NADHs FOR A YIELD OF 6 ATPs

TCA CYCLE

• 2 ATPs

• 6 NADHs FOR 18 ATPs

• 2 FADH2s FOR 4 ATPs

ANAEROBIC PATHWAYS

LACTATE FERMENTATION

• DIRECT TRANSFER FROM NADH TO PYRUVATE

• LACTATE DEHYDROGENASE

• MAJOR PATHWAY IN MANY ANAEROBIC BACTERIA

• MUSCLES

ETHANOL FERMENTATION

• NADH AND ACETALDEHYDE (A DERIVATIVE OF PYRUVATE)

• TWO STEP SEQUENCE• DECARBOXYLATION--

PYRUVATE DECARBOXYLASE

• ACETALDEHYDE REDUCTION -- ALCOHOL DEHYDROGENASE

TYPES OF FERMENTATIONS

ALCOHOLIC FERMENTATION

• FUNGI

• ALGAE

• BACTERIA

• PROTOZOA

• SUGARS --------> ALCOHOL

• ALCOHOL DEHYDROGENASE

• NADH DONOR

LACTIC ACID FERMENTATION

• REDUCTION OF PYRUVATE TO LACTATE• MORE COMMON THAN ALCOHOL

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

HOMOLACTIC ACID FERMENTERS

• LACTATE DEHYDROGENASE

• USE GLYCOLYTIC PATHWAY

• TWO KINDS OF LACTIC ACID FERMENTERS

HETEROLACTIC FERMENTERS

• MANY PRODUCE LACTATE

• ETHANOL

• VARIETY OF OTHER PRODUCTS

• USES PHOSPHOKETALOSE PATHWAY

FORMIC ACID FERMENTERS

MIXED ACID FERMENTATION

BUTANEDIOL FERMENTATION

MIXED ACID FERMENTATION

• ENTEROBACTERIACEAE

• PYRUVATE ---->

• HYDROGEN GAS

• CARBON DIOXIDE

• FORMIC HYDROGENLYASE

MIXED ACID FERMENTATION

• ETHANOL

• COMPLEX MIXTURE OF ACIDS

• ACETIC

• LACTIC

• SUCCINIC

• FORMIC

• ESCHERICHIA, SALMONELLA & ETC

ATP GENERATION IN FORMIC ACID

FERMENTATION• SOMETIME GENERATE ATP WILL

REOXIDIZING NADH

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

• DONATES TO ADP

FERMENTERS OF AMINO ACIDS

• STICKLAND REACTION

• CLOSTRIDIUM SPECIES

• GENERATE AMMONIA, HYDROGEN SULFIDE, FATTY ACIDS AND AMINES

• PUTREFACTION ODORS

ANAEROBIC RESPIRATION

ANAEROBIC RESPIRATION

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

• NITRATE

• SULFATE

• CARBON DIOXIDE

NITRATE

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

• NITRATE IS THE ELECTRON ACCEPTOR

• NITRATE REDUCTASE REPLACES CYTOCHROME OXIDASE

• NOT EFFECTIVE

• PRODUCT TOXIC

DENITRIFICATION

• REDUCED ALL THE WAY TO N2

• ACCEPTS FIVE ELECTRONS

• IS NONTOXIC

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

THE PENTOSE-PHOSPHATE PATHWAY

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

END PRODUCTS

• FRUCTOSE 6 PHOSPHATE

• GLYCERALDEHYDE 3 PHOSPHATE

• THREE CARBON DIOXIDE MOLECULES

• 6 NADPHs

• INTERMEDIATES FOR ANABOLIC REACTIONS

P GLUCOSE 6 - PHOSPHATE

`

NADPH

6-PHOSPHOGLUCONATE

NADPH

RIBULOSE 5 - PHOSPHATE

END PRODUCTS

ERYTHROSE 4 PHOSPHATE XYLOSE 5 PHOSPHATE

GLYCERALDEHYDE 3 PHOSPHATE FRUCTOSE 6 PHOSPHATE

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

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

BETA OXIDATION

BETA OXIDATION

• REMOVAL OF TWO CARBON GROUPS

• TO FORM ACETYL CoA– MAY ENTER KREBS CYCLE

• NADH AND FADH2 IS FORMED

PROTEIN METABOLISM

AMINO ACID BIOSYNTHESIS

• ADD AMINE GROUP TO KETO ACID

• SIMPLE ONE STEP TRANSMINATION REACTION– GLUTAMATE AND ASPARTATE ARE

EXAMPLES

CATABOLISM OF AMINO ACIDS

• REMOVAL OF AMINE GROUP FROM AMINO ACID

•

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