Synthetic Pathways with Amino Acids Flashcards
What amino acid is needed for glutathione synthesis?
Cysteine, glutamate, glycine
What is the function of glutathione reductase?
Reduction of Glutathione disulfide to glutathione
Uses NADPH
What two amino acids are needed for creatine synthesis?
Arginine and Glycine
What enzyme is responsible for synthesizing creatine and what does it require?
Methyltransferase
SAM
What amino acid is needed for nitric oxide synthesis?
Arginine
What is the function of Nitric oxide synthase?
Formation of NO and citrulline from arginine
Requires two reductions with NADPH
What are two important transformations for the synthesis of neurotransmitters from amino acids?
Hydroxylation
Decarboxylation
What is the rate-limiting step in catecholamine synthesis?
Tyrosine hydroxylase
Requires THB
What amino acid is required for serotonin synthesis?
Tryptophan
What two enzymes are required for serotonin synthesis?
Tryptophan hydroxylase - requires O2 and tetrahydrobiopterin
5-hydroxytryptophan decarboxylase
What amino acid is required for histamine synthesis?
Histidine
Decarboxylase reaction
What are three important functions of heme-containing proteins?
Carrying oxygen
Metabolizing drugs
Making ATP
What is the function of delta-aminolevulinate synthase?
Condensation of succinyl CoA and glycine in heme biosynthesis
Rate-limiting step
Requires PLP
How is delta-ALA-synthase regulated?
Inhibited by HEMIN - oxidized form of heme released when synthesis exceeds amount of apoprotein available
Stimulated by increased need for heme – more apoprotein made
What are Porphyrias?
Disorders of heme biosynthesis
Most are inherited and dominant
Intermediate accumulation determines clinical presentation
What are symptoms of porphyrias leading to accumulation of ALA and porphobilinogen?
Abdominal pain and psychological distrubances
Treatment with P-450 metabolized drugs
What are symptoms of porphyrias leading to accumulation of tetrapyrrole intermediates?
Skin photosensitivity
What two porphyrias cause neurovisceral symptoms?
Acute intermittent porphyria
ALA dehydratase deficiency porphyria
How does lead poisoning affect heme biosynthesis?
Inhibits Ferrochelatase and ALA dehydratase
What are symptoms of lead poisoning in adults?
Peripheral neuropathy (reversible), GI symptoms, anemia, increased reticulocytes
What are symptoms of lead poisoning in children?
Encephalopathy, behavioral changes, motor and cognitive deficits (irreversible), deposition of lead in bones
Where does heme breakdown occur and what is the source for most of it?
Macrophages and hepatocytes
Most comes from hemoglobin
Remainder comes from cytochromes and immature RBCs
What is the product of heme breakdown?
Bilirubin
How is bilirubin excreted from the liver?
Bilirubin is conjugated to two glucuronic acid molecules
Then actively transported into bile
What happens to bilirubin when bile is excreted to the gut?
Metabolized to either urobilinogen or stercobilin
Urobilinogen can be reabsorbed
What is the cause of jaundice?
Bilirubin production exceeds excretion, excess is deposited in the skin and sclera
Can be caused by hemolytic condition, obstruction of bile duct, or liver damage
