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ISU BBMB 405 - Heme and Nucleotide Biosynthesis
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BBMB 405 1st Edition Lecture 18Outline of Last Lecture XVI. Chapter 24: The biosynthesis of Amino AcidsA. Nitrogen fixation: Microorganisms use ATP and a powerful reductant to reduce atmosphere nitrogen to ammoniaB. Amino acids are made from intermediates of citric acid cycle and other major pathwaysC. Feedback inhibition regulates amino acid biosynthesisD. Amino acids are precursors of many biomoleculesOutline of Current Lecture XVI. Chapter 24: The biosynthesis of Amino AcidsD. Amino acids are precursors of many biomoleculesXVII. Chapter 25: Nucleotide BiosynthesisA. Nucleotides can be synthesized by de novo or salvage pathwaysB. The pyrimidine ring is assembled de novo or recovered by salvage pathwaysCurrent LectureXVI. Chapter 24: The biosynthesis of Amino AcidsC. Amino acids are precursors of many biomolecules1. Formation of Nitric OxideThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.2. Handout 2/23a. Physiological actions of NO: blood vessel dilation (hypertension), neurotransmitter, immune response (helps kill bacteria)b. Biochemical action: NO activates Guanylatecyclase which converts GTP to cGMP; cGMP dilates blood vesselsc. Heme synthesis: i. succinyl-CoA + Glycine  (lowercase delta)-Amino levulinate (ALA)ii. Uses ALA synthase, lose carbon dioxide and CoA, vitamin B6 requirement (coenzyme)iii. Takes place in mitochondria and then moved to cytosol where rest of reaction takes placeiv. Structure: (do not need to know)3. Porphyrins are synthesized from glycine and succinyl coenzyme Aa. Rate limiting stepb. Where is heme made? Every cell but mostly in bonesc. Heme Biosynthetic pathway (memorize)d. Uroporphyrinogen IIIi. Add Co+ for B12 in bacteriaii. Add Mg++ for chlorophyll in bacteria and plantsiii. Add Ni++ for F430 in methane producing bacteriaiv. Add Fe++ for Heme in myoglobin, hemoglobin, catalase, etc in plants, animals, and bacteriae. Heme degradationi.ii. The green color in a bruse is biliverdiniii. Happens in spleen and bone marrowiv. Only reaction that produces COv. Bilirubin: less water soluble, binds to albumin then goes to liverf. Handout 2/25i. Bilirubin (redish yellow color that contributes to plasma color) takes the glucuronate from 2UDP-glucuronate to make Bilirubin diglucuronide (water soluble intermediate) and 2UDPii. Bilirubin diglucuronide is converted to Bile then in the small intenstine to feces (composed of stercobilinogen, stercobinin, urobilin (contributes to yellow of urine), and bilirubin which all contribute to brown of feces)iii. Glucose is oxidized twice at 6C and make UDPG then converted to UDP-glucuronate which is an important for removing drugs from our system, it makes them water soluble and goes out in urine or fecesiv. When don’t get rid of bilirubin causes jaundice (icterus): excessive RBC breakage (hemolytic), impaired liver function (hepatic), liver cancer, bileduct obstruction (obstructive), immature liver function (neonatal); excess bilirubin makes skin and eyes yellowv. Bilirubin has positive (antioxidant: bilirubin converts ROOH to ROH) and negative effects (bilirubin can uncouple oxidative phosphorylation)4. Porphyrins accumulate in some inherited disorders of porphyrin metabolisma. Disorders of heme synthesis (porphyrias)b. Congenital erythropoieticporphyriasi. lack of cosynthase – can’t make cyclic moleculeii. Redish urineiii. Uropophyrinogen III not synthesizedc. Acute intermittent porphyria (most prevalent)i. Accumulation of porphobilinogen and ALAii. Abdominal pain and neurological dysfunctionXVII. Chapter 25: Nucleotide BiosynthesisA. Nucleotides can be synthesized by de novo or salvage pathways1. Nomenclature of Bases, nucleosides, and nucleotides (memorize)2. Summary of nucleotide synthesisa. Pyrimidine nucleotide: Asp + CP Orotate + PRPP  UMP  UTTP or UTP  CTPb. Purine nucleotide: R-5-P (reduction of ATP to AMP)  PRPP  ATP or GTP3. Difference between a neucleotide and a nucleoside is a phosphate groupB. The pyrimidine ring is assembled de novo or recovered by salvage pathways1. De novo pathway for pyrimidine nucleotide synthesisa.b. Pyrimidine synthesis in cytosol2. Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation3. The side chain of glutamine can be hydrolyzed to generate ammonia: glutamine is source of ammonia and is channeled through enzyme to react with other sites4. Intermediates can move between active sites by


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ISU BBMB 405 - Heme and Nucleotide Biosynthesis

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