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Similar to CREATININE METABOLISM, uric acid biosynthesis and melanin synthesis.pptx
CREATININE METABOLISM, uric acid biosynthesis and melanin synthesis.pptx
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- 2. Creatinine • Biosynthesis – Occursin kidney and liver – Require 3 amino acids – Takes up by muscle and brain from blood – Store energy as creatinephosphate
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- 4. GUANIDOACETATE CREATINE S-ADENOSYL METHIONINE (SAM) S-ADENOSYL HOMOCYSTEINE (SAH) GUANIDOACETATE METHYLTRANSFERASE IN LIVER
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- 6. Normal level • Serum –Creatine – 0.2-0.6 mg/dl – Creatinine – 0.7-1.4 mg/dl • Urine – Creatine - <50mg/day – Creatinine – 1-2 g/day
- 7. Uric Acid Biosynthesisand Its Disorder
- 9. Factors affecting formationof uric acid • Depends on – De novo synthesis of purines – The metabolism of endogenous DNA, RNA, and other purine containing molecule such as ATP – The breakdown of dietary nucleic acid
- 10. Significance of uricacid • Potent antioxidant – Very effective scavenger of free radicals.
- 11. Excretion • Via thekidney : major • Via the gut : smaller amount
- 12. Clinical significance • Normalrange 4 to 7 mg/dl • At physiological pH, it is mostly ionized and present in plasma as sodium urate. • Elevated serum urate concentration is known as hyperuricaemia • Uric acid and urate are relatively insoluble and readily precipitate out of the aquous solutions such as urine or synovial fluid • Condition called gout
- 13. Cause of hyperuricaemia •Due to increased uric acid formation – Primary (genetic) • Due to enzyme defects in: – PRPP synthase – PRPP aminotransferase – HGPRTase – Secondary • Due to increased: – Dietary intake – Nucleic acid turnover – ATP breakdown – Deficiency of glucoase -6-phosphatase
- 14. • Due todecreased uric acid excretion – Primary idiopathic – Secondary due to: • Renal insufficiency • Metabolic acidosis • Lactic acidosis • Ketoacidosis • Starvation • Diabetes mellitus • Increased tubular reabsorption
- 15. Gout • Elevated uricacid level associated with either increased formation of uric acid or decreased renal excretion • Classification – Primary gout – Secondary gout • Symptoms – Patients with primary gout often show deposition of urate as tophi in soft tissues that affects the joints and leads to painful arthritis – Kidneys are also affected lead to renal failure
- 16. Primary Gout • Inheriteddue to an inborn error of metabolism caused by defective enzymes of purine biosynthesis – Partial deficiency of HGPRTase – Loss of feed back regulation • PRPP synathase • PRPP amidotransferase
- 17. Secondary Gout • Elevateddestruction of cells or defective elimination of uric acid – Over production of urate due to increased destruction or turnover of cells • Myeloproliferative disorders ( e.g. leukaemia, polycythaemia) • Cytotoxic drug ( antimetabolites) therapy • Psoriasis – Defective elimination of uric acid due to • Reduced glomerular filtration rate • In diuretic therapy due to reduced distal tubular secretion of uric acid – Hyper-catabolic states and starvation • Lactic acidosis and ketoacidosis – Inherited metabolic disorders • Eg. Von gierke’s disease
- 18. Treatment • Foods richin nucleotides and nucleic acids such as liver or coffee and tea, which contain the purines caffeine and theobromin are withheld from the diet • Use of drug allopurinol
- 19. LESCH-NYHAN SYNDROME • InheritedX-linked disorder • Complete deficiency of HGPRTase • Symptoms – Hyperuricaemia – Gout – Urinary tract stones – Mental retardation – Spasticity – Self-mutilation • Treatment – allopurinol
- 20. Hypouricaemia • Decreased serumuric acid less than 2mg/dl • Causes – Xanthinuria – Adenosine deaminase (ADA) deficiency – Purine nucleoside phosphorylase deficiency
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- 23. Albinism • greek: albino– white • Inborn error, due to alck of synthesis of the pigment melanin • Autosomal recessive disorder with frequency of 1 in 20000
- 24. • Causes – Deficiencyor lack of the enzyme tyrosinase – Decrease in melanosomes of melanocytes – Impairment in melanin polymerization – Lack of protein matrix in melanosomes – Limitation of substrate (tyrosine) availability – Presence of inhibitors of tyrosinase
- 25. • Clinical manifestation –Skin cancer – Photophobia – White hair