1. Department of Biochemistry
Zhihong Li（李志红）
Department of Biochemistry

2. Main Topics Metabolism of Nucleotides (4h)
DNA replication(4h); RNA transcription(4h); Protein synthesis (4h)
Gene expression and regulation (4h); Recombinant DNA technology (4h)
Signal transduction(4h); Oncogene(2h); Gene and disease (2h)
Diabetes mellitus (2h); Lipoproteins Metabolism (4h)
Cholesterol Metabolism (2h); Bile acids Metabolism (2h)
Plasma Proteins and Immuno Proteins (2h)
Inter-assesment
Free Radicals and Antioxidants (2h) ; Mineral Metabolism(2h)
Water and Electrolyte Balance(2h); Acid Base Balance (2h)
Heme Synthesis (2h); Bile Pigments Metabolism (2h)
Liver function tests (2h); Metabolism of xenobiotics (2h)
Hormones (6h); Biochemical changes during Pregnancy (2h)
Biochemistry of Cerebrospinal fluid(CSF)(2h)

3. Lecture 1 Metabolism of Nucleotides

5. Contents Review: Structure of nucleic acid Degradation of nucleic acid
Synthesis of Purine Nucleotides
Degradation of Purine Nucleotides
Synthesis of Pyrimidine Nucleotides
Degradation of Pyrimidine Nucleotides

6. Nucleoside and Nucleotide
Nitrogenous base ribose
Nitrogenous base ribose phosphate

7. Purines vs Pyrimidines

8. Structure of nucleotides
pyrimidine OR
purine
Ribose or
2-deoxyribose
N-b-glycosyl
bond

9. Section 1 Degradation of nucleic acid

10. Degradation of nucleic acid
Nucleoprotein
In stomach
Gastric acid and pepsin
Nucleic acid
Protein
In small intestine
Endonucleases: RNase and DNase
Nucleotide
Nucleotidase
Phosphate
Nucleoside
Nucleosidase
Base
Ribose

11. Lesch-Nyhan syndrome

12. Section 3 Degradation of Purine Nucleotides

13. The end product of purine metabolism (2,6,8-trioxypurine)
Adenosine Deaminase
The end product of purine metabolism
(2,6,8-trioxypurine)

14. Uric acid
Uric acid is the excreted end product of purine catabolism in primates, birds, and some other animals.
The rate of uric acid excretion by the normal adult human is about 0.6 g/24 h, arising in part from ingested purines and in part from the turnover of the purine nucleotides of nucleic acids.
The normal concentration of uric acid in the serum of adults is in the range of 3-7 mg/dl.

15. GOUT
The disease gout, is a disease of the joints, usually in males, caused by an elevated concentration of uric acid in the blood and tissues.
The joints become inflamed, painful, and arthritic, owing to the abnormal deposition of crystals of sodium urate.
The kidneys are also affected, because excess uric acid is deposited in the kidney tubules.

16. The uric acid and the gout
Hypoxanthine
Xanthine
Out of body
In urine
Uric acid 
Over 8mg/dl, in the plasma
Diabetese nephrosis ……
Gout, Urate crystallization
in joints, soft tissue, cartilage and kidney

17. Advanced Gout Clinically Apparent Tophi1 2 1 3
The advanced gout stage is often referred to as chronic tophaceous gout to indicate the presence of this clinical manifestation, which will remain unresolved in the absence of urate-lowering therapy.
Tophi are characterized by solid urate deposits in connective tissues that produce irregular nodularities and joint destruction. In addition, the skin overlying the tophi may become ulcerated and exude a white, chalky material.
Shown here are some common sites of tophi, including dermal tophi on the finger, periarticular tophi on the hands, and tophi on the helix of the ear.
The patient who was experiencing the intradermal tophi on the knees was diagnosed and treated by multiple generalists and specialists for osteoarthritis. This photo was taken during his self-referred first visit to a rheumatologist and reinforces the point that gout is a disease that is under-recognized.1 The patient with polyarticular involvement of his hands had been misdiagnosed and treated for rheumatoid arthritis for 8 years.2
The tophi exhibited on this slide are clinically apparent, but this may not always be the case, as was seen in the previous case study examples of the tophi that formed in the bone of the knee and the palm of the hand.
1. Patient case study courtesy of Brian Mandell, MD, PhD, Cleveland Clinic.
2. Patient case study courtesy of N. Lawrence Edwards, MD, University of Florida.
1. Photos courtesy of Brian Mandell, MD, PhD, Cleveland Clinic.
2. Photo courtesy of N. Lawrence Edwards, MD, University of Florida.
3. ACR Clinical Slide Collection on the Rheumatic Diseases, 1998. 17

18. Points Synthesis of Purine Nucleotides
De novo synthesis: Site, Characteristics, Element sources of purine bases
Salvage pathway: definition, significance, enzyme, Lesch-Nyhan syndrome
Formation of deoxyribonucleotide: NDP level
Antimetabolites of purine nucleotides:
Purine, Amino acid, and Folic acid analogs
Degradation of Purine Nucleotides
Uric acid, gout
Synthesis of Pyrimidine Nucleotides
De novo synthesis: Characteristics, Element sources of pyrimidine bases
Salvage pathway
Antimetabolites of pyrimidine nucleotides
Catabolism of Pyrimidine Nucleotides