BIOC 2300 Lecture Notes - Lecture 23: Serine Hydroxymethyltransferase, Neural Tube Defect, Methionine Synthase
3 May 2018
School
Department
Course
Professor
Amino Acid Metabolism
March 16-23, 2016
Amino acids synthesized from serine
• ……
Some functions of the serine family:
• serine: precursor of sphingolipids and phosphatidylserine; the enantiomer D-serine is a
neuromodulator an dinfluences neurotransmission in the brain
• Glycine: neurotransmitter
• Cysteine: precursor for glutathione, redox active thiol group in proteins from disulphide
bonds…
• ..
Glutathione: important antioxidant
• due to thiol group, tripeptide can for
• ..
Free Radicals:
• oxygen can be highly reactive when it has unpaired electrons – can damage lipids,
protiens, DNA
• superoxide anion
• peroxide
• hydroxyl darial
• antioxtidants and gluthathione reacts with perioxides to non-reactive thiols
o antioxidants: react with free radicals to pair up with electrons Ascorbic acid
(vitamin C), tocopherols (vitamin E), peptides with thiol groups (glutathione),
enzymes
o Glutathione converts reactive hydroperoxides to harmless hydroxides and is
oxidized to GSSSG, regeneration of reduced gluthione requires NADPH
Serine: precursor of sphingolipids and phosphatidylserine (enantiomer D-serine is a
neuromodulator)
Glycine: neurotransmitter
Cysteine: precursor for glutathione, redox active thiol group, in proteins due to disulphide bonds
*All of them play a role in 1-C metabolism
• Described metabolic pathways that are connected to reaction involving transfer of single
carbons = methyl groups in different oxidation states equivalent to methanol,
formaldehyde and formate
• Includes folate metabolism, methylation cycle and transsulfuration
• Most important 1C groups: folic acid, S-adenosylmethionine
• Folic acid = B9 vitamin; converted to tetrahydrofolate (THF)
• S-andosylmethionine is a derivative of methionine
find more resources at oneclass.com
find more resources at oneclass.com
Tetrahydrofolate
• Functions as carrier of 1C units in several reactions of amino acid and nucleotide
metabolism
• THF is derived from folate (B9)
• Folate THF: addition of methyl
• Folate is important during development = correlated with birth defects
o Decreased prevalence of neural tube defects following folate fortification of flour
Serine glycine and THF methylene-THF *via serine hydroxymethyltransferase
Folate metabolism and methylation cycle are closely connected
• Serine can indirectly supply methyl for methionine synthesis
• Folate is required as well as vitamin B6 and B12
• The methylation cycle costs energy
• Folate metabolism requires B12 (homocysteine methionine)
Methionine Cycle and Methylation:
• Do not need to memorize structures
• Homocysteine Methionine (via methionine synthase and vitamin B12)
Important of methylation reactions:
• DNA methylations (epigenetics)
o Methylation of cytosine 5- methylcytosine
o Catalyzed by DNA methyltransferase
o Regulates transcription without changing the DNA sequence
o Highly influenced by environment during development
• Phosphatidylcholine synthesis (from phosphatidylethanolamine)
• Thymidine synthesis (dTMP from dUMP) – purine synthesis
• Synthesis of carnitine, creatin, epinephrine and other products
Amino Acids are precursors of some signalling molecules:
• Glutamate and glycine are neurotransmitters in the brain
• Other neurotransmitters and neuromodulators are derived from amino acids:
o GABA – from glutamate
o Dopamine – from tyrosine
o Serotonin and melatonin – from tryptophan
o D-serine, D-aspartate
• Arginine is the precursor of nitric oxide (signalling molecule) *see reaction
Nucleotide biosynthesis requires ribose-5-phosphate, amino acids and methyl groups
Purine and Pyrimidines must be synthesized in equal amounts.
• ATP (purine) is a feedforward activator for pyrimidine synthesis. CTP (pyrimidine_
inhibits prymidine synthesis = negative feedback
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Glutathione: important antioxidant: due to thiol group, tripeptide can for. Serine: precursor of sphingolipids and phosphatidylserine (enantiomer d-serine is a neuromodulator) Cysteine: precursor for glutathione, redox active thiol group, in proteins due to disulphide bonds. *all of them play a role in 1-c metabolism: described metabolic pathways that are connected to reaction involving transfer of single carbons = methyl groups in different oxidation states equivalent to methanol, formaldehyde and formate. Includes folate metabolism, methylation cycle and transsulfuration: most important 1c groups: folic acid, s-adenosylmethionine, folic acid = b9 vitamin; converted to tetrahydrofolate (thf, s-andosylmethionine is a derivative of methionine. Serine glycine and thf methylene-thf *via serine hydroxymethyltransferase. Folate metabolism and methylation cycle are closely connected: serine can indirectly supply methyl for methionine synthesis, folate is required as well as vitamin b6 and b12, the methylation cycle costs energy, folate metabolism requires b12 (homocysteine methionine)
