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Exam III Preparation
Exam III will focus on nitrogen metabolism, basically the material covered in Chapters
20 and 22. The topics begin with amino acid oxidation and end with the synthesis of
nucleotides. Nitrogen is the theme for all of the reactions. It should be understood that the
below list, while comprehensive over this section of the course, must not be considered
complete. It is intended only as a study guide.
Amino Acid Catabolism
Start your studies by knowing how amino acids are prepared for metabolism. Know what is
meant by a 26S proteosome, the 20S proteosome, the N-rule, reactions involved in protein
ubiquination. Know the mechanism of an aminotransferase, the role of glutamate/-Kg pair in
the reaction, the different forms and functions of vitamin B6 pyridoxal-PO4, pyridoxamine-PO4
Be able to demonstrate a reaction involving an aminotransferase enzyme. Know the function of
glutamate dehydrogenase, how the enzyme catalyzes the oxidative deamination of glutamate.
Know how glutamine and glutamate contribute NH3 to the urea cycle. Know urea cycle
reactions (urea cycle tutorial will help), the amino acids, where ATP is needed in the cycle.
Know amino acid families to follow the carbon skeletons of non-essential amino acids. Know,
for example, the glutamate family, the pyruvate family. Know the degradation of the
phenylalanine, the intermediates down to fumarate and acetoacetate. Know how cysteine forms
from methionine. Know the causes of phenylketonuria alcaptonuria, maple-syrup urine disease.
Nitrogen Fixation and Assimilation
Know the mechanism of nitrogen fixation, the nitrogenase (dinitrogenase) complex. Know how
ammonia is incorporated into the structure of amino acids. Know the major nitrogen donors and
be able to demonstrate each in a reaction. Know the mechanism of glutamine synthetase, the
covalent control of the enzyme, the role of AT, UT, PII, PII-UMP, etc.
Amino Acid Biosynthesis and Derivation
Know the synthesis of all non-essential amino acids by families. Know the structure and
synthesis of tetrahydrofolate (THF), one-carbon metabolism THF intermediates, methylation
reactions via SAM, B12 and methyl-THF, the methyl cycle. Know how amino acids become the
carbon and nitrogen atoms in the structures of hormones, neurotransmitters, heme, creatine.
Nucleotide Biosynthesis
Know the details of purine and pyrimidine ring synthesis. The synthesis of PRPP from ribose-5PO4. Know the function carbamoly-PO4 synthetase II, the final products of the pathway. Know
how 5’-IMP becomes 5’-GMP, 5’-AMP. Know how 5’-UMP becomes CTP. Know how a cell
makes dTMP, dTDP, and dTTP and is protected from making TMP, TDP, or TTP. Know the
monophospho- and diphosphonucleotide kinases. Know the reactions of purine and pyrimidine
degradation. Know the salvage pathways. Know how a deoxynucleotide is formed. The role of
ribonucleotide reductase, the free-radicals as reaction intermediates. Know how the pathway of
nucleotide biosynthesis has led to develop anticancer and anti-arthritis drugs such as
Aminopterin, Methotrexate and purine and pyrimidine analogs such as arabinosides and AZT.
GENERAL COMMENTS
Some students will insist that “memorization” is absolutely essential to learning biochemistry. I
will concur. But, I will not agree that ONLY memory can be used. The pathways of amino
acids build on reactions you already leaned in the Krebs cycle, glycolysis, and to a lesser extent,
beta oxidation. Use these. Once you spot an intermediate that you recognize, e.g., DHAP,
pyruvate, -ketoglutarate, acetoacetate, you know the rest of the way home. Consider these
suggestions for putting memory and logic into your studies:
1. Know a pathway first by studying the stating and ending compounds in the pathway. The
ending compound could be a recognized intermediate of the Krebs cycle, glycolysis, etc.
2. Work backwards, applying logic to each step.
3. Classify the reactions. Are you adding phosphate, are you oxidizing an –OH group, are you
replacing an amino group, etc.
4. Identify the cofactor or other substrates that may be needed for that step. Oxidations require
NAD+, reductions often require NADPH, amino additions require an –NH2 donor, phosphate
addition requires ATP, phosphate removal uses H2O.
5. If you insist on memorizing the pathway, memorize only the middle compound of the
pathway. For example, in the glutamate pathway, memorize the structure of glutamate-semialdehyde. Then, see how this compound is formed from the starting compound (ornithine)
and how it becomes the product of the pathway (glutamate). P.S. Knowing that ornithine comes
from arginine allows you to go one step further and bring in a second amino acid into your
understanding.
Remember, by knowing you have reason and logic on you side will help you figure out
complicated pathway problems who answers may not be apparent on first sight. It will ease your
tension on exams and allow you to work at you best to solve pathway questions.