2. Nitrogen Fixation Nitrogen fixation is the reduction of ____________:
Bacteria are responsible for the reduction and typically form symbiotic relationships that result in nodules on the roots of leguminous plants
Reduction is catalyzed by the nitrogenase enzyme complex
N2 to NH4+is a six-electron reduction

3. The Path of Electrons from Ferrodoxin to N2

4. Summary
Nitrogen enters the biosphere by the process of nitrogen fixation.
Atmospheric nitrogen is converted to ammonia in its conjugate acid form, ammonium ion.
The nitrogenase enzyme found in root nodules of leguminous plants catalyzes crucial reactions in nitrogen fixation

5. Feedback Inhibition in Nitrogen Metabolism
If there is a high level of end product amino acid or nucleotide, the cell saves energy by not making the compound through a feedback mechanism
In summary, because the biosynthetic pathways for many nitrogen-containing compounds are long and complex, feedback inhibition helps ______ ____________

6. Amino Acid Biosynthesis
Common features of amino acid biosynthesis include: _________________ & _____________________ transfers
Glutamate is formed by reductive amination of -ketoglutarate and NH4+
Amidation of glutamate gives glutamine
• All amino acids are grouped into families based on their __________________________________

7. Amino Acid Biosynthesis

8. Amino Acids and The Citric Acid Cycle

9. Role of Pyridoxal Phosphate in Amino Acid Rxns
The biologically active form of vitamin ______ is pyridoxal phosphate (PyrP)
PyrP participates in the catalysis of a wide variety of reactions of amino acids, including transaminations and decarboxylations
Pyridoxal phosphate forms an imine (a Schiff base) with the -amino group of an amino acid
Rearrangement gives an isomeric imine
Hydrolysis of the isomeric imine gives an -ketoacid and pyridoxamine
All reactions are ______________________

10. Role of Pyridoxal Phosphate in Amino Acid Rxns

11. Role of Pyridoxal Phosphate in Amino Acid Rxns
Transamination reactions switch ____________ ___________ from one amino acid to an -keto acid

12. A Transamination Rxn Produces Serine

13. Serine to Glycine
Serine to glycine is an example of a one-carbon transfer
The one-carbon acceptor is tetrahydrofolate, which is derived from folic acid

14. Serine to Glycine
Reduction of folic acid gives tetrahydrofolic acid (THF), the ________________ form of the coenzyme
Tetrahydrofolate is a carrier of the one-carbon groups shown in Figure (see next slide)

15. Structure and Reactions of Folic Acid

16. Serine to Cysteine
In ____________ & ____________, serine is acetylated to form O-acetylserine
The source of sulfur in plants and bacteria differ from that in animals
Sulfur donor comes from PAPS (3’-Phospho-5’adenylylsulfate)

17. Serine to Cysteine

18. Methionine
Methionine cannot be produced in animals, making it an _________ amino acid
Methionine reacts with ATP to form S-adenosylmethionine (SAM)

19. Cysteine in Animals SAM is a _________________________________
The methyl group can be transferred to a number of acceptors producing S-adenosylhomocysteine

20. Summary
Two of the most important classes of reactions in the biosynthesis of amino acids are transamination reactions and one-carbon transfers
The amino acids glutamate and glutamine are the principal donors of amino groups in transamination reactions
Carriers of one-carbon groups include biotin, SAM, and derivatives of folic acid

21. Essential Amino Acids
The biosynthesis of proteins requires the presence of all the constituent amino acids
Some species, including humans, cannot produce all of the amino acids and they must come from ____________ and are called essential amino acids

22. Amino Acid Catabolism
First step is removal of the -amino group by transamination
-amino group is transferred to -ketoglutarate to give glutamate and an -ketoacid
The breakdown of carbon skeletons follows two pathways, depending on the type of end product
_________________ amino acid: one whose carbon skeleton is degraded to pyruvate or oxaloacetate, both of which may then be converted to glucose
_________________ amino acid: one whose carbon skeleton is degraded to acetyl-CoA or acetoacetyl-CoA, both of which may then be converted to ketone bodies

23. Amino Acid Catabolism

24. Amino Acid Catabolism
The -amino group which has been transferred to -ketoglutarate has one of two fates:
It may be used for biosynthesis
It may be excreted as a part of a nitrogen-containing product

25. The Urea Cycle
The urea cycle is the central pathway in nitrogen metabolism
The nitrogen atoms come from several sources
Steps of the cycle are outlined in Figure (next slide)

26. The Urea Cycle Fig 23.18, p.688

27. The Urea Cycle Fig 23.19, p.690

28. Summary The carbon skeleton has two fates in the breakdown process.
Some carbon skeletons give rise to pyruvate or oxaloacetate, which can be used in ______________
Others give rise to acetyl-CoA or acetoacetyl-CoA, which can form _______________
The urea cycle, which has links to the citric acid cycle, plays a central role in nitrogen metabolism.
It is involved in both the anabolism and the catabolism of _____________ _______________

29. Purine Biosynthesis
Where do the atoms of purines come from?

30. How is IMP converted to AMP and GMP
IMP is the precursor to AMP and GMP, and the conversion takes place in 2 stages

31. Regulation of ATP and GTP
Purine nucleotide biosynthesis is regulated by __________________
In Summary:
• The growing ring system of purines is attached to ribose phosphate during the synthesis process
• The biosynthesis of nucleotides requires considerable expenditures of energy by organisms in long and complex pathways.
• Feedback inhibition at all stages plays a key role in regulating the pathway

32. Purine Catabolism
The catabolism of purine nucleotides proceeds by hydrolysis to the nucleoside and subsequently to the free base, which is further degraded
Salvage reactions are important in the metabolism of purine nucleotides because of the amount of energy required for the synthesis of the purine bases
In Summary:
• Purines are degraded to uric acid in primates and are further degraded in other organisms. Overproduction of uric acid causes gout in humans
• Salvage reactions allow some purines to be reused

33. Purine Catabolism

34. Purine Salvage

35. Pyrimidine Biosynthesis and Catabolism
The overall scheme of pyrimidine biosynthesis differs from that of purines because the pyrimidine ring is assembled ___________ it is attached to ribose-5-phosphate
Carbon and nitrogen atoms of the pyrimidine ring come from carbamoyl phosphate and aspartate
The production of N-carbamoylaspartate is the _________________ step in pyrimidine biosynthesis

36. Pyrimidine Biosynthesis and Catabolism

37. Pyrimidine Biosynthesis and Catabolism

38. Pyrimidine Biosynthesis and Catabolism
Feedback inhibition in pyrimidine nucleotide biosynthesis takes place in several ways

39. Pyrimidine Biosynthesis and Catabolism
Pyrimidine catabolism involves the breakdown of the molecule first to the nucleoside, and then to the base
This is similar to what happens in purine catabolism

40. Summary
The ring system of pyrimidines is assembled before it is attached to ribose phosphate
During breakdown, the nucleoside is formed first, then the base.
Ring-opening reactions of the base complete the degradation.

41. Conversion of Ribonucleotides to Deoxyribonucleotides
Ribonucleoside diphosphates are reduced to 2’-deoxyribonucleoside diphosphates in all organisms
_______________ is the reducing agent

42. Conversion of Ribonucleotides to Deoxyribonucleotides

43. Conversion of dUDP to dTTP
The addition of a methyl group to uracil to produce thymine requires ___________________ as the one-carbon carrier.
This process is a target for cancer chemotherapy

44. Thymidylate Synthase