Chapter 23: Nitrogen Metabolism

Nitrification

Conversion of ammonia to nitrates

Denitrification

Process by which nitrates and nitrites are broken down to molecular nitrogen

Nitrogen fixation

Reduction of N₂ to NH₃

Bacteria

Responsible for the reduction of N₂ to NH₃ and form symbiotic relationships that result in nodules on the roots of leguminous plants

Nitrogenase enzyme complex

Catalyzes the reduction of N₂ to NH₃

6

N₂ is converted to ammonium ion in a __-electron reduction

Feedback inhibition

Process by which the final product of a series of reactions inhibits the first reaction in the series

Glutamate

Formed by reductive amination of α-ketoglutarate and NH₄⁺

Glutamine

Amidation of glutamate gives _____

Transamination

Transfer of amino groups from one molecule to another

Transamination, one-carbon transfers

Amino acid biosynthesis involves _____ reactions and _____

Pyridoxal phosphate (PyrP)

Biologically active form of vitamin B6

Pyridoxal phosphate (PyrP)

Participates in the catalysis of a wide variety of reactions of amino acids, including transaminations and decarboxylations

• forms an imine (a Schiff base) with the α-amino group of an amino acid

Isomeric imine

Rearrangement of an imine gives an _____

α-ketoacid and pyridoxamine

Hydrolysis of isomeric imine gives an _____ and _____

Glutamate

Nitrogen donor in the biosynthesis of serine

3-phosphoserine and α-ketoglutarate

In the biosynthesis of serine, transamination reaction in which glutamate is the nitrogen donor produces _____ and _____

Hydrolysis of phosphate group of phosphoserine

Gives rise to serine (in serine biosynthesis)

Serine hydroxymethylase

Catalyzes the transfer of a one-carbon unit from serine to an acceptor

Tetrahydrofolate

Carrier of one-carbon groups derived from folic acid

Tetrahydrofolic acid (THF)

Reduction of folic acid gives _____, the reactive form of the coenzyme

Serine acetyltransferase

Catalyzes acetylation of serine to form O-acetylserine

3’-phospho-5’-adenylyl sulfate

Sulfur donor used in the conversion of O-acetylserine to cysteine

Methionine

• cannot be produced in animals; must be obtained from dietary sources

• essential amino acid

S-adenosylmethionine (SAM)

Methionine reacts with ATP to form _____ when ingested

S-adenosylmethionine (SAM)

Methyl group carrier

S-adenosylhomocysteine

S-adenosylmethionine is a methyl group carrier, and the methyl group can be transferred to a number of acceptors, producing _____

Homocysteine

Hydrolysis of S-adenosylhomocysteine produces _____

Serine and homocysteine

Cysteine can be synthesized from _____ and _____

Essential amino acids

Amino acids that cannot be synthesized by the body and must be obtained in the diet

Removal of nitrogen by transamination

1st step in amino acid catabolism

Glutamate, α-ketoacid

In amino acid catabolism, α-amino group is transferred to α-ketoglutarate to give _____ and _____

Glucogenic amino acid

Carbon skeleton is degraded to pyruvate or oxaloacetate, both of which may then be converted to glucose

Ketogenic amino acid

Carbon skeleton is degraded to acetyl-CoA or acetoacetyl-CoA, both of which may then be converted to ketone bodies

Leucine and Lysine

Ketogenic amino acids

• Isoleucine

• Phenylalanine

• Tryptophan

• Tyrosine

Both glucogenic and ketogenic amino acids

Urea cycle

• Pathway that leads to excretion of waste products of nitrogen metabolism, especially those of amino acids

• Central pathway in nitrogen metabolism

• Has links to the TCA cycle

• Involved in both anabolism and catabolism of amino acids

Ornithine transcarbamoylase

(Urea Cycle) Catalyzes carbamoyl phosphate + ornithine → citrulline

Argininosuccinate synthetase

(Urea Cycle) Catalyzes aspartate + citrulline → argininosuccinate

Argininosuccinase

(Urea Cycle) Catalyzes argininosuccinate → arginine + fumarate

Arginase

(Urea Cycle) Catalyzes arginine → ornithine + urea

Purine catabolism

Proceeds by hydrolysis to the nucleoside, and subsequently to the free base, which is further degraded

Xanthine

Degradation of guanine produces _____

Hypoxanthine

Degradation of adenine produces _____

Xanthine; uric acid

Hypoxanthine can be oxidized to _____, which in turn is oxidized to _____

Uric acid

Product of catabolism of nitrogen-containing compounds, especially purines

Gout

Accumulation of uric acid in joints causes _____ in humans

Salvage reactions

• like recycling processes in the body

• reuse parts of old or broken-down molecules (like purines and pyrimidines from DNA and RNA) to make new ones

• important in the metabolism of purine nucleotides because of the amount of energy required for the synthesis of the purine bases

Adenine phosphoribosyltransferase

(Salvage reaction) Adenine reaction is catalyzed by _____

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

(Salvage reaction) Guanine and hypoxanthine reactions are catalyzed by _____

Ribose phosphate

In the synthesis of purine nucleotides, the growing ring system of purines is attached to _____

Inosine monophosphate (IMP)

Precursor to AMP and GMP, and the conversion takes place in 2 stages

Adenylosuccinate synthetase

(AMP synthesis) Catalyzes P-ribose → adenylosuccinate

Adenylosuccinate lyase

(AMP synthesis) Catalyzes adenylosuccinate → adenylate (AMP)

IMP dehydrogenase

(GMP synthesis) Catalyzes P-ribose → Xanthylate

GMP synthetase

(GMP synthesis) Catalyzes Xanthylate → Guanylate (GMP)

7 ATP

Production of IMP starting with ribose-5-phosphate requires the equivalent of _____ ATP

Hydrolysis of GTP

Conversion of IMP to AMP requires _____

8 ATP

Formation of AMP from ribose-5-phosphate requires the equivalent of _____ ATP

two high-energy bonds

Conversion of IMP to GMP requires _____, given that a reaction occurs in which ATP is hydrolyzed to AMP and PPi

9 ATP

Production of GMP from ribose-5-phosphate requires the equivalent of _____ ATP

Carbamoyl phosphate; aspartate

Carbon and nitrogen atoms of the pyrimidine ring come from _____ and _____

cytosol; glutamine

Production of carbamoyl phosphate for pyrimidine biosynthesis takes place in _____, and the nitrogen donor is _____

Carbamoyl phosphate + aspartate → N-carbamoylaspartate

The committed step in pyrimidine biosynthesis

Ring-opening reactions

_____ of the base complete the degradation (Pyrimidine catabolism)

2’-deoxyribonucleosides diphosphates

Ribonucleoside diphosphates are reduced to _____ in all organisms

• NADPH is the reducing agent

thymine; tetrahydrofolate

Addition of a methyl group to uracil to produce _____ requires _____ as the one-carbon carrier

Thymidylate synthetase, dihydrofolate reductase

Inhibitors of _____ and _____ have been used in cancer chemotherapy