M1,Nitrogen Fixation and Assimilation
M2,Amino acid metabolism
M3,The urea cycle
M4,Hemes and chlorophylls
Section M Nitrogen Metabolism
1,The nitrogen cycle
2,Nitrogen fixation
3,Nitrogen assimilation 同化作用
Nitrogen fixation and assimilation
The nitrogen cycle
The nitrogen cycle is the movement
of nitrogen through the food chain
from simple inorganic compounds,
mainly ammonia,to complex organic
compounds,
脱氨作用
分解代谢
Nitrogen fixation
Nitrogen fixation is the conversion of N2
gas into ammonia,a process carried out
by some soil bacteria,cyanobacteria蓝细
菌,and the symbiotic 共生的 bacteria
Rhizobium 根瘤菌 that invade the root
nodules of leguminous豆类 plants,
Nitrogen fixation
This process is carried out by the nitrogenase
固氮酶 complex,which consists of a
reductase and an iron-molybdenum 钼 -
containing nitrogenase,At least 16ATP
molecules are hydrolyzed to form two
molecules of ammonia,Leghemoglobin 豆血
红蛋 白 is used to protect the nitrogenase in
the Rhizobium from inactivation by O2,
nitrogenase
铁氧还蛋
白
Nitrogen assimilation
Ammonia is assimilated by all organisms
into organic nitrogen-containing
compounds(amino acids,nucleotides,etc.)
by the action of glutamate dehydrogenase
(to form glutamate) and glutamine
synthetase (to form glutamine),
Amino acid family
Amino acid degradation
? Amino acids are degraded by the
removal of the α-amino group and
the conversion of the resulting
carbon skeleton into one or more
metabolic intermediates,
Amino acid degradation
? Amino acids are termed glucogenic if their
carbon skeletons can give rise to the net
synthesis of glucose,and ketogenic of they can
give rise to ketone bodies,Some amino acids
give rise to more than one intermediate and
these lead to the synthesis of glucose as will as
ketone bodies,Thus these amino acids are both
glucogenic and ketogenic,
pathway
Transamination
? The α-amino group of most amino acids
is transferred to α-ketoglutarate to form
glutamate and the corresponding α-keto
acid
? α-amino acid + α-ketoglutarate α-keto
acid + glutamate
? Enzyme,transaminases
Aminotansferase
Vitamine B6
PLP
Oxidative deamination of glutamate
glutaminase
Amino acid oxidases
NH3
Metabolism of phenylalanine
四
氢
生
物
蝶
呤
Inborn errors of metabolism
? Inherited metabolic disorders
遗传代谢紊乱
? Alkaptonuria 尿黑酸症
? Homogentisate oxidase 尿黑酸氧化酶
? Phenylketonuria 苯丙酮尿
? Phenylalanine hydroxylase
苯丙氨酸羟化酶
The urea cycle
1,Ammonia excretion
2.The urea cycle
3,Link to the citric acid cycle
4,Hyperammonemia
5,Formation of creatine phosphate
6,The activated methyl cycle
7,Uric acid
Ammonia excretion
? Ammonotelic animal 排氨 ammonia
? Uricotelic animal 排尿酸 uric acid
? Ureotelic animal 排尿素 urea
? terrestrial reptile 陆生爬行动物
? Aquatic animal 水生动物
Ammonia excretion
? Amminia------ammonotelic organisma—
aquatic animals
? Uric acid ------uricotelic organisms birds
and terrestrial reptiles
? Urea-----ureotelic organisms—terrestrial
vertebrates
The urea cycle
? In the urea cycle ammonia is first combined
with CO2 to form carbamoyl phosphate,This
then combines with ornithine to form citrulline,
Citrulline then condenses with aspartate,the
source of the second nitrogen atom in urea,to
form argininosuccinate,This compound is in
turn split to arginine and fumarate,and the
arginine then splits to form urea and
regenerate ornithine,
NH4+ + HCO3- + H2O + 3ATP +aspartate
urea + 2ADP + AMP + 2Pi +PPi +
fumarate
Urea cycle
Urea cycle
? The reaction place,mitochondria,cytosol
? The enzymes are involved in reaction,
1.Carbarroyl phosphate synthetase 氨甲酰磷酸合酶
2.ornithine transcarbamoylae 鸟氨酸转氨甲酰酶
3.argininosuccinate synthetase 精氨琥珀酸合成酶
4.argininosuccinase 精氨琥珀酸酶
5.arginase 精氨酸酶
Urea cycle 2
Urea cycle 3
Urea cycle 4
Urea cycle 5
Link to the citric acid cycle
Oxaloacetate has several
possible fates
? Transamination to aspartate which can
then feed back into the urea cycle;
? Condensation with acetyl CoA to form
citrate which then continues on round
the citric acid cycle ;
? Conversion into glucose via
gluconeogenesis ;
? Conversion into pyruvate
Hyperammonemia
? A block in any of the urea cycle
enzymes leads to an increase in
the amount of ammonia in the
blood,so-called hyperammonemia
ammonia
The reason of brain damage
in hyperammonemia,
1,Excess ammonia leads to the formation
of glutamate and glutamine,
2,It may compromise energy production,
3,It also leads to increase [H+ ]
Formation of creatine phosphate
? The urea cycle is also the starting point
for the synthesis of another important
metabolite creatine phosphate,This
phosphate provides a reservoir of high-
energy phosphate in muscle cells,
ATP
? As the energy released upon is
hydrolysis is greater than that
released upon the hydrolysis of ATP
(ΔG for creatine phosphate
hydrolysis=-10.3kal mol-1 compared
with –7.3 kcal mol-1 for ATP
hydrolysis ),
Creatine phosphate
? The first step in the formation of creatine
phosphate is the condensation of arginine
and glycine to form guanidinoacetate胍基乙酸,
Ornithine is released in this reaction and can
then be re-utilized by the urea cycle,The
guanidinoacetate is then methylated by the
methyl group donor S-adenosyl methionine to
form creatine,which is in turn phosphory-
lated,by creatine kinase to form creatine
phosphate,
Creatine phosphate
The activated methyl cycle
? S-Adenosyl methionine serves as
donor of methyl groups in numerous
biological reactions [e.g.in the for-
mation of creatine phosphate and in
the synthesis of nucleic acids].It is
formed through the action of the
activated methyl cycle,
The activated methyl cycle
? During donation of its Methylgroup to
another compound,S-adenosyl methionine
is converted into S-adenosyl homocysteine,
To regenerate S-adenosyl methionine,the
adenosyl group is removed from the S-
adenosyl homocysteine to form homo-
cysteine高半胱氨酸,
The activated methyl cycle
? This is then methylated by the enzyme
homocysteine methyltransferase,one of only
two vitamin B12 containing enzymes found
in eukaryotes,to form methionine,The
resulting methionine is then activated to S-
adenosyl methionine,With the release of all
three of the phosphate from ATP,
Methyl cycle
Uric acid
? Uric acid is the main nitrogenous waste
product of uricotelic organisms (reptiles,
birds and insects),but is also formed in
ureotelic organisms from the breakdown
of the purine bases from DNA and RNA,
? Gout 痛风
HEMES AND CHLOROPHYLLS
1,Tetrapyrrol
2,Biosynthesis of hemes and
chorophylls
3,Heme degradation
Tetrapyrroles
? The tetrapyrroles are a family of pigments
based on a common chemical structure that
includes the hemes and chlorophylls,Hemes
are cyclic tetrapyrroles that contain iron and
are commonly found as the prosthetic group of
hemoglobin,myoglobin and he cytochromes,
Heme is as the prosthetic roup
Globin 珠蛋白
Protein
Heme Cytochomes 细胞色素
Catalases 过氧化氢酶
Enzyme
Peroxidase 过氧化物酶
chlorophylls
? The chlorophylls are modified
tetrapyrroles containing magnesium
that occur as light-harvesting and
reaction center pigments of
photosynthesis in plants,algae and
photosynthetic bacteria,
structure
Biosynthesis of hemes and
chlorophylls
The staring point for heme and
chlorophyll synthesis is aminolaevulinic
acid 氨基乙酰丙酸 (ALA) which is made in
animals from glycine and succinyl CoA by
the enzyme ALA synthase,
Biosynthesis of hemes
and chlorophylls
? This pyridoxal 吡 哆 醛 pyosphate-
requiring enzyme is feedback regulated
by heme,Two molecules of ALA then
condense to form porphobilinogen 胆色
素原 in a reaction catalyzed by ALA
dehydratase 脱水酶,
Biosynthesis of hemes
and chlorophylls
? Porphobilinogen deaminase catalyzed the
condensation of four porphobilinogen to
form a linear tetrapyrrole,This compound
then cyclizes to form uroporphyhrinogen
尿卟啉原 III,the precursou of hemes,
chlorophylls and vitamin B12,
Biosynthesis of hemes
and chlorophylls
? Further modifications take place to form
protoporphyrin原卟啉 IX,The biosynthetic
pathway then branches,and either iron is
inserted to form heme,or magnesium is
inserted to begin a series of conversions to
form chlorophyII,
pathway
protoporphyrin
Heme degradation
? Heme is broken down by heme oxygenase
to the linear tetrapyrrole biliverdin胆绿素,
This green pigment is them converted to the
red-orange bilirubin 胆红素 by biliverdin
reductase,The lipophilic bilirubin is carried
in the blood bound to serum albumin,and is
then converted into a more water-soluble
compound in the liver by conjugation to
glucuronic acid 葡萄糖醛酸,
heme
Heme
? The resulting bilirubin
? Diglucuronide 胆红素二葡糖苷酸 is
secreted into the bile,and finally excreted
in the feces,Jaundice is due to a build up
of insoluble bilirubin in the skin and
whites of the eyes,
Heme
? In higher plants heme is broken down to the
phycobiliprotein藻胆蛋白 phytochrome which
is involved in coordinating light responses,
while in algae it is metabolized to the light-
harvesting pigments phycocyanin and
phycoerythrin,
M2,Amino acid metabolism
M3,The urea cycle
M4,Hemes and chlorophylls
Section M Nitrogen Metabolism
1,The nitrogen cycle
2,Nitrogen fixation
3,Nitrogen assimilation 同化作用
Nitrogen fixation and assimilation
The nitrogen cycle
The nitrogen cycle is the movement
of nitrogen through the food chain
from simple inorganic compounds,
mainly ammonia,to complex organic
compounds,
脱氨作用
分解代谢
Nitrogen fixation
Nitrogen fixation is the conversion of N2
gas into ammonia,a process carried out
by some soil bacteria,cyanobacteria蓝细
菌,and the symbiotic 共生的 bacteria
Rhizobium 根瘤菌 that invade the root
nodules of leguminous豆类 plants,
Nitrogen fixation
This process is carried out by the nitrogenase
固氮酶 complex,which consists of a
reductase and an iron-molybdenum 钼 -
containing nitrogenase,At least 16ATP
molecules are hydrolyzed to form two
molecules of ammonia,Leghemoglobin 豆血
红蛋 白 is used to protect the nitrogenase in
the Rhizobium from inactivation by O2,
nitrogenase
铁氧还蛋
白
Nitrogen assimilation
Ammonia is assimilated by all organisms
into organic nitrogen-containing
compounds(amino acids,nucleotides,etc.)
by the action of glutamate dehydrogenase
(to form glutamate) and glutamine
synthetase (to form glutamine),
Amino acid family
Amino acid degradation
? Amino acids are degraded by the
removal of the α-amino group and
the conversion of the resulting
carbon skeleton into one or more
metabolic intermediates,
Amino acid degradation
? Amino acids are termed glucogenic if their
carbon skeletons can give rise to the net
synthesis of glucose,and ketogenic of they can
give rise to ketone bodies,Some amino acids
give rise to more than one intermediate and
these lead to the synthesis of glucose as will as
ketone bodies,Thus these amino acids are both
glucogenic and ketogenic,
pathway
Transamination
? The α-amino group of most amino acids
is transferred to α-ketoglutarate to form
glutamate and the corresponding α-keto
acid
? α-amino acid + α-ketoglutarate α-keto
acid + glutamate
? Enzyme,transaminases
Aminotansferase
Vitamine B6
PLP
Oxidative deamination of glutamate
glutaminase
Amino acid oxidases
NH3
Metabolism of phenylalanine
四
氢
生
物
蝶
呤
Inborn errors of metabolism
? Inherited metabolic disorders
遗传代谢紊乱
? Alkaptonuria 尿黑酸症
? Homogentisate oxidase 尿黑酸氧化酶
? Phenylketonuria 苯丙酮尿
? Phenylalanine hydroxylase
苯丙氨酸羟化酶
The urea cycle
1,Ammonia excretion
2.The urea cycle
3,Link to the citric acid cycle
4,Hyperammonemia
5,Formation of creatine phosphate
6,The activated methyl cycle
7,Uric acid
Ammonia excretion
? Ammonotelic animal 排氨 ammonia
? Uricotelic animal 排尿酸 uric acid
? Ureotelic animal 排尿素 urea
? terrestrial reptile 陆生爬行动物
? Aquatic animal 水生动物
Ammonia excretion
? Amminia------ammonotelic organisma—
aquatic animals
? Uric acid ------uricotelic organisms birds
and terrestrial reptiles
? Urea-----ureotelic organisms—terrestrial
vertebrates
The urea cycle
? In the urea cycle ammonia is first combined
with CO2 to form carbamoyl phosphate,This
then combines with ornithine to form citrulline,
Citrulline then condenses with aspartate,the
source of the second nitrogen atom in urea,to
form argininosuccinate,This compound is in
turn split to arginine and fumarate,and the
arginine then splits to form urea and
regenerate ornithine,
NH4+ + HCO3- + H2O + 3ATP +aspartate
urea + 2ADP + AMP + 2Pi +PPi +
fumarate
Urea cycle
Urea cycle
? The reaction place,mitochondria,cytosol
? The enzymes are involved in reaction,
1.Carbarroyl phosphate synthetase 氨甲酰磷酸合酶
2.ornithine transcarbamoylae 鸟氨酸转氨甲酰酶
3.argininosuccinate synthetase 精氨琥珀酸合成酶
4.argininosuccinase 精氨琥珀酸酶
5.arginase 精氨酸酶
Urea cycle 2
Urea cycle 3
Urea cycle 4
Urea cycle 5
Link to the citric acid cycle
Oxaloacetate has several
possible fates
? Transamination to aspartate which can
then feed back into the urea cycle;
? Condensation with acetyl CoA to form
citrate which then continues on round
the citric acid cycle ;
? Conversion into glucose via
gluconeogenesis ;
? Conversion into pyruvate
Hyperammonemia
? A block in any of the urea cycle
enzymes leads to an increase in
the amount of ammonia in the
blood,so-called hyperammonemia
ammonia
The reason of brain damage
in hyperammonemia,
1,Excess ammonia leads to the formation
of glutamate and glutamine,
2,It may compromise energy production,
3,It also leads to increase [H+ ]
Formation of creatine phosphate
? The urea cycle is also the starting point
for the synthesis of another important
metabolite creatine phosphate,This
phosphate provides a reservoir of high-
energy phosphate in muscle cells,
ATP
? As the energy released upon is
hydrolysis is greater than that
released upon the hydrolysis of ATP
(ΔG for creatine phosphate
hydrolysis=-10.3kal mol-1 compared
with –7.3 kcal mol-1 for ATP
hydrolysis ),
Creatine phosphate
? The first step in the formation of creatine
phosphate is the condensation of arginine
and glycine to form guanidinoacetate胍基乙酸,
Ornithine is released in this reaction and can
then be re-utilized by the urea cycle,The
guanidinoacetate is then methylated by the
methyl group donor S-adenosyl methionine to
form creatine,which is in turn phosphory-
lated,by creatine kinase to form creatine
phosphate,
Creatine phosphate
The activated methyl cycle
? S-Adenosyl methionine serves as
donor of methyl groups in numerous
biological reactions [e.g.in the for-
mation of creatine phosphate and in
the synthesis of nucleic acids].It is
formed through the action of the
activated methyl cycle,
The activated methyl cycle
? During donation of its Methylgroup to
another compound,S-adenosyl methionine
is converted into S-adenosyl homocysteine,
To regenerate S-adenosyl methionine,the
adenosyl group is removed from the S-
adenosyl homocysteine to form homo-
cysteine高半胱氨酸,
The activated methyl cycle
? This is then methylated by the enzyme
homocysteine methyltransferase,one of only
two vitamin B12 containing enzymes found
in eukaryotes,to form methionine,The
resulting methionine is then activated to S-
adenosyl methionine,With the release of all
three of the phosphate from ATP,
Methyl cycle
Uric acid
? Uric acid is the main nitrogenous waste
product of uricotelic organisms (reptiles,
birds and insects),but is also formed in
ureotelic organisms from the breakdown
of the purine bases from DNA and RNA,
? Gout 痛风
HEMES AND CHLOROPHYLLS
1,Tetrapyrrol
2,Biosynthesis of hemes and
chorophylls
3,Heme degradation
Tetrapyrroles
? The tetrapyrroles are a family of pigments
based on a common chemical structure that
includes the hemes and chlorophylls,Hemes
are cyclic tetrapyrroles that contain iron and
are commonly found as the prosthetic group of
hemoglobin,myoglobin and he cytochromes,
Heme is as the prosthetic roup
Globin 珠蛋白
Protein
Heme Cytochomes 细胞色素
Catalases 过氧化氢酶
Enzyme
Peroxidase 过氧化物酶
chlorophylls
? The chlorophylls are modified
tetrapyrroles containing magnesium
that occur as light-harvesting and
reaction center pigments of
photosynthesis in plants,algae and
photosynthetic bacteria,
structure
Biosynthesis of hemes and
chlorophylls
The staring point for heme and
chlorophyll synthesis is aminolaevulinic
acid 氨基乙酰丙酸 (ALA) which is made in
animals from glycine and succinyl CoA by
the enzyme ALA synthase,
Biosynthesis of hemes
and chlorophylls
? This pyridoxal 吡 哆 醛 pyosphate-
requiring enzyme is feedback regulated
by heme,Two molecules of ALA then
condense to form porphobilinogen 胆色
素原 in a reaction catalyzed by ALA
dehydratase 脱水酶,
Biosynthesis of hemes
and chlorophylls
? Porphobilinogen deaminase catalyzed the
condensation of four porphobilinogen to
form a linear tetrapyrrole,This compound
then cyclizes to form uroporphyhrinogen
尿卟啉原 III,the precursou of hemes,
chlorophylls and vitamin B12,
Biosynthesis of hemes
and chlorophylls
? Further modifications take place to form
protoporphyrin原卟啉 IX,The biosynthetic
pathway then branches,and either iron is
inserted to form heme,or magnesium is
inserted to begin a series of conversions to
form chlorophyII,
pathway
protoporphyrin
Heme degradation
? Heme is broken down by heme oxygenase
to the linear tetrapyrrole biliverdin胆绿素,
This green pigment is them converted to the
red-orange bilirubin 胆红素 by biliverdin
reductase,The lipophilic bilirubin is carried
in the blood bound to serum albumin,and is
then converted into a more water-soluble
compound in the liver by conjugation to
glucuronic acid 葡萄糖醛酸,
heme
Heme
? The resulting bilirubin
? Diglucuronide 胆红素二葡糖苷酸 is
secreted into the bile,and finally excreted
in the feces,Jaundice is due to a build up
of insoluble bilirubin in the skin and
whites of the eyes,
Heme
? In higher plants heme is broken down to the
phycobiliprotein藻胆蛋白 phytochrome which
is involved in coordinating light responses,
while in algae it is metabolized to the light-
harvesting pigments phycocyanin and
phycoerythrin,
