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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
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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
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
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 ______ ____________
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 __________________________________
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 ______________________
Role of Pyridoxal Phosphate in Amino Acid Rxns • Transamination reactions switch ____________ ___________ from one amino acid to an -keto acid
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
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 23.11 (see next slide)
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)
Methionine • Methionine cannot be produced in animals, making it an _________ amino acid • Methionine reacts with ATP to form S-adenosylmethionine (SAM)
Cysteine in Animals • SAM is a _________________________________ • The methyl group can be transferred to a number of acceptors producing S-adenosylhomocysteine
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
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
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
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
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 23.18 (next slide)
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 _____________ _______________
Purine Biosynthesis • Where do the atoms of purines come from?
How is IMP converted to AMP and GMP • IMP is the precursor to AMP and GMP, and the conversion takes place in 2 stages
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
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
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
Pyrimidine Biosynthesis and Catabolism • Feedback inhibition in pyrimidine nucleotide biosynthesis takes place in several ways
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
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.
Conversion of Ribonucleotides to Deoxyribonucleotides • Ribonucleoside diphosphates are reduced to 2’-deoxyribonucleoside diphosphates in all organisms • _______________ is the reducing agent
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