Citric Acid Cycle
Content
Citric acid cycle
Click to edit Master subtitle style
3/31/12
Citric acid cycle
v Respiration is process which allows aerobic
organisms to obtain energy from the energy trapped in the food they ingest order to enter the citric acid cycle which forms the pool of most of the energy needed by the organism digestion , glycolysis , citric acid cycle and lastly the electron transport system
v Different foods follow different pathways in
v Carbohydrates for example undergo
v When proteins break down into amino acids
3/31/12 some of amino acids like glutamic acid enter
Krebs cycle
q Its called the tricarboxylic acid cycle because
of the citric acid a tricarboxylic acid involved in the cycle
q It’s a series of chemical reactions used by all
aerobic organisms to generate energy through the oxidation of acetate to CO2 and H2O fats , carbohydrates and proteins
q The acetate is derived from the breakdown of
3/31/12
Krebs cycle
Carbon atoms become oxidised by the
removal of hydrogen or the combination with oxygen from carbon
Both processes involve the loss of electrons The cycle also produces precursors like NADH
a reducing agent for the eletron transport system
A precursor is a chemical compound
preceding another in a metabolic pathway
3/31/12
Krebs cycle
Free electrons cannot exist so the electrons
released on oxidation must be accepted by NAD+ to form NADH by NAD+ is catalysed by enzymes called dehydrogenases the eletron acceptor
The reaction involving acceptance of electrons
The term oxidase is used when oxygen itself is
3/31/12
Krebs cycle
v Oxidases catalse a small proportion of
oxidation reactions
v Acetate from the breakdown of fats , proteins
and carbohydrates must first be converted to to acetyl Co enzyme A before it enters the cycle
v Co enzyme A activates and transfers the acyl
groups into the cycle source of acetate
v Pyruvate from carbohydrates is the main v The process occurs in stages one to ten 3/31/12
3/31/12
Stage one(citrate formation)
Ø The cycle begins with the formation of citrate
a 6 carbon compound
Ø Acetyl –CoA a 2 carbon compund and
oxaloaceacetate a 4 carbon compound undergo a condensation reaction
Ø The reaction is catalysed by the enzyme
citrate synthatase
Ø the reaction proceeds in two parts Ø Acetyl-CoA +oxaloacetate
citryl CoA citrate
3/31/12
+CoA-SH
Stage two(formation of cisaconitic acid)
Ø Citrate is converted to cis-aconitic acid Ø The reaction is catalysed by aconitase
through a reversible hydration reaction hydratase
3/31/12
Stage three(formation of iso citric acid)
q Formation of iso citric acid involves
dehydration of cis aconitic acid the reaction
q The enzyme aconitase dehydratase catalyse
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Stage four(formation of oxalosuccinic acid)
v Isocitric acid is oxidised by the removal of
hydrogen to form oxalocuccinic acid
v NAD+
becomes the eletron acceptor to form the the first NADH in the cycle dehydrogenase
v The reaction is catalsed by iso citrate
3/31/12
Stage five(formation of alpha ketoglutaric acid)
v v v v
It’s a very important point in the citric acid cycle because its linked to metabolic pathways of certain amino acids like glutamic acid Glutamic acid can be oxidised to alpha ketoglutarate and it can join the cycle Oxalosuccinic acid is oxidised by removal of carbon dioxide using the enzyme isocitrate oxidase
3/31/12
Stage six(formation of succinyl CoA)
Coenyme A is incorporated into the cycle
through an esterification reaction decarboxylation to produce CO2
Alpha ketoglutarate is oxidised by Its also oxidised by removal of hydrogen to
form the second NADH
The enzyme alpha ketoglutarate
dehydrogenase is used
3/31/12
Stage seven(formation of succinic acid)
q The first ATP is produced q The thioester bond is broken yielding energy
for formation of ATP succinic thiokinase
q The enzyme for breaking this bond is is q Energy is first made in the form of GTP q The reversible reaction of GTP and ADP
produces GDP and ATP
q The reaction is catalsed by nucleoside
diphosphokinase
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Stage eight(formation of fumaric acid)
Ø Succinic acid is oxidised to fumarate by
succinate dehydrogenase in which FAD+ participates as a coenzyme acts as a competitive inhibitor of succinic acid system is produced
Ø The step is inhibited by malonic acid which
Ø In the reaction FADH2 for the eletron transport
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Stage nine(formation of malic acid)
Fumaric acid is dehydrated to L-malic acid by
the enzyme fumarase in a reversible reaction
3/31/12
Stage ten(regenaration of the 4 carbon compound oxaloacetate)cycle is the v The last step in the
dehydrogenation of malic acid by malate dehydrogenase , a NAD+ dependent enzyme
v The third and last NADH is produced v The reaction regenarates oxaloacetate the
startingbpoint of citric acid cycle
3/31/12
Krebs cycle
The whole cycle for each molecule of acetly
CoA produces 3 NADH ,one FADH2 ,two CO2 and one ATP molecules in the gel like matrix of the mitochondrion
In eukaryotic cells the citric acid cycle occurs Bacteria also uses the citric acid cycle to
generate energy but since they lack mitochondrion the cycle takes place in the cytosol of the bacterial cell pathway because it takes part in both 3/31/12 catabolic and anabolic reactions
The cycle can be termed an ampibolic
Regulation of the cycle
3/31/12
3/31/12
Click to edit Master subtitle style
3/31/12
Citric acid cycle
v Respiration is process which allows aerobic
organisms to obtain energy from the energy trapped in the food they ingest order to enter the citric acid cycle which forms the pool of most of the energy needed by the organism digestion , glycolysis , citric acid cycle and lastly the electron transport system
v Different foods follow different pathways in
v Carbohydrates for example undergo
v When proteins break down into amino acids
3/31/12 some of amino acids like glutamic acid enter
Krebs cycle
q Its called the tricarboxylic acid cycle because
of the citric acid a tricarboxylic acid involved in the cycle
q It’s a series of chemical reactions used by all
aerobic organisms to generate energy through the oxidation of acetate to CO2 and H2O fats , carbohydrates and proteins
q The acetate is derived from the breakdown of
3/31/12
Krebs cycle
Carbon atoms become oxidised by the
removal of hydrogen or the combination with oxygen from carbon
Both processes involve the loss of electrons The cycle also produces precursors like NADH
a reducing agent for the eletron transport system
A precursor is a chemical compound
preceding another in a metabolic pathway
3/31/12
Krebs cycle
Free electrons cannot exist so the electrons
released on oxidation must be accepted by NAD+ to form NADH by NAD+ is catalysed by enzymes called dehydrogenases the eletron acceptor
The reaction involving acceptance of electrons
The term oxidase is used when oxygen itself is
3/31/12
Krebs cycle
v Oxidases catalse a small proportion of
oxidation reactions
v Acetate from the breakdown of fats , proteins
and carbohydrates must first be converted to to acetyl Co enzyme A before it enters the cycle
v Co enzyme A activates and transfers the acyl
groups into the cycle source of acetate
v Pyruvate from carbohydrates is the main v The process occurs in stages one to ten 3/31/12
3/31/12
Stage one(citrate formation)
Ø The cycle begins with the formation of citrate
a 6 carbon compound
Ø Acetyl –CoA a 2 carbon compund and
oxaloaceacetate a 4 carbon compound undergo a condensation reaction
Ø The reaction is catalysed by the enzyme
citrate synthatase
Ø the reaction proceeds in two parts Ø Acetyl-CoA +oxaloacetate
citryl CoA citrate
3/31/12
+CoA-SH
Stage two(formation of cisaconitic acid)
Ø Citrate is converted to cis-aconitic acid Ø The reaction is catalysed by aconitase
through a reversible hydration reaction hydratase
3/31/12
Stage three(formation of iso citric acid)
q Formation of iso citric acid involves
dehydration of cis aconitic acid the reaction
q The enzyme aconitase dehydratase catalyse
3/31/12
Stage four(formation of oxalosuccinic acid)
v Isocitric acid is oxidised by the removal of
hydrogen to form oxalocuccinic acid
v NAD+
becomes the eletron acceptor to form the the first NADH in the cycle dehydrogenase
v The reaction is catalsed by iso citrate
3/31/12
Stage five(formation of alpha ketoglutaric acid)
v v v v
It’s a very important point in the citric acid cycle because its linked to metabolic pathways of certain amino acids like glutamic acid Glutamic acid can be oxidised to alpha ketoglutarate and it can join the cycle Oxalosuccinic acid is oxidised by removal of carbon dioxide using the enzyme isocitrate oxidase
3/31/12
Stage six(formation of succinyl CoA)
Coenyme A is incorporated into the cycle
through an esterification reaction decarboxylation to produce CO2
Alpha ketoglutarate is oxidised by Its also oxidised by removal of hydrogen to
form the second NADH
The enzyme alpha ketoglutarate
dehydrogenase is used
3/31/12
Stage seven(formation of succinic acid)
q The first ATP is produced q The thioester bond is broken yielding energy
for formation of ATP succinic thiokinase
q The enzyme for breaking this bond is is q Energy is first made in the form of GTP q The reversible reaction of GTP and ADP
produces GDP and ATP
q The reaction is catalsed by nucleoside
diphosphokinase
3/31/12
Stage eight(formation of fumaric acid)
Ø Succinic acid is oxidised to fumarate by
succinate dehydrogenase in which FAD+ participates as a coenzyme acts as a competitive inhibitor of succinic acid system is produced
Ø The step is inhibited by malonic acid which
Ø In the reaction FADH2 for the eletron transport
3/31/12
Stage nine(formation of malic acid)
Fumaric acid is dehydrated to L-malic acid by
the enzyme fumarase in a reversible reaction
3/31/12
Stage ten(regenaration of the 4 carbon compound oxaloacetate)cycle is the v The last step in the
dehydrogenation of malic acid by malate dehydrogenase , a NAD+ dependent enzyme
v The third and last NADH is produced v The reaction regenarates oxaloacetate the
startingbpoint of citric acid cycle
3/31/12
Krebs cycle
The whole cycle for each molecule of acetly
CoA produces 3 NADH ,one FADH2 ,two CO2 and one ATP molecules in the gel like matrix of the mitochondrion
In eukaryotic cells the citric acid cycle occurs Bacteria also uses the citric acid cycle to
generate energy but since they lack mitochondrion the cycle takes place in the cytosol of the bacterial cell pathway because it takes part in both 3/31/12 catabolic and anabolic reactions
The cycle can be termed an ampibolic
Regulation of the cycle
3/31/12
3/31/12
