17 Making other Biomolecules Flashcards
Tyrosine is the precursor of
- Dopamine
- Norepinephrine
- Epinephrine
Precursor of GABA
Glutamate
Precursor of histamine
Histidine
Precursor of serotonin
Tryptophan
Describe the formation of heme
Glycine reacts with succinyl CoA to form delta-aminolevulinate
2 molecules of delta-aminolevulinate condense to form porphobilinogen
4 molecules of porphobilinogen combine to form protoporphyrin
Fe ion is inserted into protoporphyrin to form heme
Causes and symptoms of porphyria/vampire disease
Mutations or misregulations of enzymes in the heme biosynthesis pathway -> accumulation of precursor uroporphyrinogen I in red blood cells, body fluids and liver
Urine becomes discolored
Teeth may show red fluorescence under UV
Skin is sensitive to UV
craving for heme
Degredation of heme & excretion
Heme oxygenase converts heme to biliverdin
Biliverdin reductase converts biliverdin to bilirubin
Bilirubin is excredted through urine and bile
- degradation to urobilin -> major pigment of urine
- degradation to stercobilin by intestinal microbiota -> color of faeces
Jaundice cause
- Impaired liver function (liver cancer, hepatitis)
- Blocked bile secretion (gallstones, pancreatic cancer)
- Insufficient glucouronyl bilirubin transferase to process bilirubin (in infants) -> treated with UV to cause photochemical breakdown of bilirubin
Precursor of
- amino groups
- purines
- pyrimidines
- Glutamine
- Glycine
- Aspartate
Where does biosynthesis of nucleotides occur?
mostly in the liver
Origin of ring atoms in purines
N - aspartate, amide N of glutamine
C - formate, CO2
N-C=C - glycine
How are purines and pyrimidines synthesized de novo?
Purines - built on ribose base
Pyrimidines - pyrimidine rings are first synthesized before being attached onto the ribose base
Reaction steps of de novo synthesis of purinesPurine salvage pathways
- 5-phosphoribosyl 1-pyrophosphate (PRPP) react with glutamine
- Addition of 3 carbons from glycine
- Inosinate (IMP) with full purine ring formed
- AMP and GMP are synthesized from IMP
- AMP and GMP are phosphorylated to diphosphate then triphosphate (ATP and GTP)
Purine can be salvaged from
free bases and nucleosides
How does the pathway for AMP and GMP degradation merge?
Xanthine production -> oxidized into uric acid -> excreted by kidneys
Cause, symptoms and treatments of gout
Cause - excess uric acid
Paintful joints due to deposits of sodium urate crystals
Treated with avoidance of purine-rich foods (seafood, liver) / allopurinol (xanthine oxidase inhibitor)
Steps in de novo synthesis of pyrimidine nucleotides
- Aspartate and carbamoyl phosphate provide atoms for pyrimidine ring structure
- PRPP is attached to the pyrimidine ring (orotate)
- converted to uridylate (UMP)
- UMP phosphorylated to UTP -> converted to CTP
How ribonucleotides are converted to deoxyribonucleotides?
- Ribose is reduced to deoxyribose (diphosphate level, NDP) (catalyzed by ribonucleotide reductase)
- Phosphorylated to triphosphate level (dNTP)
- dNTPs are used for DNA synthesis
- dUTP -> dTTP
Degradation of pyrimidine bases
dephosphorylated -> nucleosides are cleaved to produce ribose-1-phosphate and free pyrimidine bases
- cytosine -> uracil -> CO2 + NH4 + beta-alanine
- thymine -> CO2 + NH4 + beta-aminosobutyrate
