1. pluripotent stem cell to unipotential stem cell
2. forms proerythroblasts
3. it divides four or five times (requires all the machinery for DNA synthesis, without it, there will not be division)
   1. as they divide, the cell gets smaller
4. results in a cell with no subcellular organelles, but still has ribosomes: reticulocytes
5. reticulocytes go into circulation, and after 24 hours, mature into RBC

• hypoxanthine (one carbon)
• xanthine (two carbons)
• uric acid (all three carbons)

Hypoxanthine is related to what purine? xanthine is related to what purine?

How

• hypoxanthine relats to adenine (difference of NH2 and double bond O at same C)
• xanthine related to guanosine (difference btw NH2 and double bond O at same C)

1. via non-oxidative part of HMP shunt produces ribose 5 P (remember, this is fully reversible)
2. ribose 5 P and ATP produces PRPP and AMP via PRPP synthetase
3. PRPP and Gln produce Glu, PR-1 amine, pyrophosphate via amidotransferase
   1. committed step, so major conrol point for pathway
   2. gives one of the N of the ring
4. after nine steps, we get end product: inosine monophosphate

2 Gln

Asp

Gly

2 Gly

CO2

2 folate

1. IMP, Asp, and GTP form adenylosuccinate and GTP via adenylosuccinate synthetase
2. adenylosuccinate forms fumarate and AMP via adenylosuccinase

GTP is the energy souce and Asp is the energy source.

1. IMP and NAD converted to XMP and NADH via IMP dehydrogenase
2. XMP, ATP, and Gln form Glu, ADP, and GMP via amidotransfrase

ATP is energy source and Gln is N source

• NMP and ATP to NDP and ADP via mononucleotide kinases

Can be AMP kinase, GMP kinase, UMP kinase, CMP kinase, TMP kinase

• NDP and ATP form NTP and ADP via dinucleotide kinase

Can be GDP, CDP, UDP, TDP

• increases in AMP negatively feedback on adenylosuccinase
• increases in GMP negatively feedback on amindotransferases (in major control step, PRPP to PP-1 amine, and syn. step of GMP)

1. two options
   1. AMP to IMP via daminase
   2. AMP to adenosine via phosphodiesterase
2. two options
   1. IMP to inosine via phosphodiesterase
   2. adenosine to inosine via deaminase
3. inosine to hypoxanthine via purine nucleotide phosphorylase
4. hypoxanthine to xanthine via xanthine oxidase (flavoprotein)
5. xanthine to uric acid via xanthine oxidase

1. GMP to guanosine via phosphodiesterase
2. guanosine to guanine via purine nucleotide phosphorylase
3. guanine to xanthine via deaminase
4. xanthine to uric acid via xanthine oxidase (flavoprotein)

• accumulation of uric acid in the body due to overproduction (genetic) or reduced excretion in the kidney
  • for some reason, keep making PRPP and keep making AMP and GMP
  • the more made, the more that is broken down
• it forms sodium urate, which is not very soluble
• it will form crystals in the joints
• can be triggered by infection, diet, cancer

• hypoxanthine and PRPP form IMP via hypoxanthine guanine phosphoribosyl tranferase (HGPRT)
• adenosine and PRPP form AMP via adenine phosphoribosyl transferase
• guanine and PRPP form GMP via HGPRT

1. use Gln, CO2, ATP to form ADP and carbamoyl phosphate via CPS II
2. CP and Asp form open ring intermediate via Aspartate transcarbamolylase
   1. major control point (RATE LIMITING)
3. via dihydroorotase, form dihydrooratic acid
4. dihydrooratic acid and NAD form NADH and oratic acid via dihydroorotate DH
5. oratic acid and PRPP form OMP via orotate phosphoribosyltransferase
6. OMP forms CO2 and UMP via orotidylate decarboxylase
7. UTP, Gln, and ATP form Glu, ADP, and CTP via CTP synthetase

1. NDP (N can be A, C, U, G) and thioredoxin (reduced form) form deoxy-NDP and thioredoxin (oxidized form)
   1. thioredoxin (oxidized form) and NADPH forms NADP and thioredoxin (reduced form)

This is the only way I can get deoxynucleotides. If its defective, it is detremental to life.

• dUMP and methylene tetrafolate form dTMP and difolate via thymidylate synthase
  • Major target for cancer therapy (if its defective, we cant make thymine for DNA, so stops DNA replication)
• dTMP and ATP form dTDP and ADP via mononucleotide kinase