Lecture 5 (3A) - Amino Acids as Biosynthetic Precursors Flashcards
Amino acids are precursors of many biologically important molecules
- haem
- sphingosine
- histamine
- dopamine
- thyroxine
- serotonin
- glutathione (GSH)
- pyrimidines - cytosine
- purines - adenine
Molecules start small…
get big
too big = not energetically favorable
Haem
Ring formed from
GLYCINE and acetate
(acetate to citric acid cycle as acetyl CoA)
(succinyl CoA)
Haem ring
formation equation
succinyl CoA + glycine
→
α-aminolevulinate
- monomer is α-aminolevulinate (ALA)
- goes on to instruct overall structure of the haem ring
Dimerization of ALA in haem ring
- 2 monomers make a single ring component
- pyrrole ring
- porphobiliniogen → 4 (of ALA)
- linear tetrapyrrole → forms ring, D ring reversed (so recognize as specific way around)
- mito → cytosol
- acetate → methyl with SAM
- back to mito in production of haem, then inclusion of iron into ring (requires energy)
Diseases (haem)
the porphyrias
porphobilinogen deaminase deficiency
- most common
- dimer only, no tetrapyrrole formation
- abdominal pain, neuroligical disfunction
- prot wine colored skin
- King George
Diseases (haem)
the porphyrias
erythropoietic protoporphyria
limited life expectancy
Diseases (haem)
the porphyrias
congenital erythropoietic porphoria
- red colored urine
- teeth fluorescent red
- skin photosensitive (only come out at night)
- excessive hair growth
Sphingosine
- an intermediate in sphingolipids
- main group = acetate
- reactive terminal from serine
- head group, used in many amino acids
GABA-γ-aminobutyric acid
- decarboxylation process (lose carboxylic acid)
- formed from glutamate
- important neurotransmitter
- problems with urea cycle - disrupts production
→ buildup of glutamate
→ excessive side reactions, imbalanced
- PLP dependent
- Tay sach’s disease
Histamine
- formed from histidine
- by decarboxylation - lose carboxylic acid
- PLP dependent
- allergic reaction
- control of acid in stomach
- drug mimics histamine → controls acid in stomach
Dopamine
- formed from tyrosine
- addition of hydroxyl to ring
- important neurotransmitter
- precursor for melanin
- removal of carboxyl (CO2) from amino acid
tyrosine
→
hyrdoxyl added to ring
→
L-DOPA
→
decarboxylated to form DOPAMINE
→
CO2 removed
→
hydroxylation of side chain
→
SAM methylates
Dopamine
makes various small molecules of the body
- hydroxylation to form norepinephrin
- methylation to form **epinephrine **(using SAM)
Dopamine is releated to the disease…
Parkinson’s disease
- can’t pass blood brain barrrier, L-DOPA can, bosts dopamine production
Tyroxine
tetraiodothyronine
- also formed from tyrosine
- side chain on main chain, linked together to form main structure
- formed in the thyroid (hence name)
- functions in general metabolic stimulation (controls body)
- need iodine in diet
Serotonin
- for mood
- formed from tryptophan
- hydroxylation followed by decarboxylation
- important neurotransmitter
- controls smooth muscle contraction
- addition to 5-hydroxyl group to ring
- removal of carboxyl (CO2) from amino acid
NAD+
nicotinamide unit
- formed also from tryptophan
- oxido/reductive agent
Glutathione (GSH)
γ-glutamylcystrinylglucine
tripeptide
- tripeptide
- Glutamate (E)
- Cysteine (C)
- Glycine (G)
- ECG bond together, not straight
- gamma side chain linkage to form the amino acid bond
- γ-amide bond in glutamate
(GSH)
- involved in detoxifications, transport, and metabolic processes
- energy-requiring reaction 3 times = very energy intensive
glutamate + cysteine → γ-glu-cyn pairing
- adds glycine (with ATP) → glutathione (synthetase)
inside the cell
→ made cyclic 5-oxo-proline (stable)
energy to break → back to glutamate = fully cyclinc
(to make glutathione - glutamate regenerated)
- glutathione transferred out of the cell (detox)
- γ glutyl transpeptidase brings somethingback into the cell and brings external amino acids with it == into cell again
- amino acid removed, left inside (amino acid out → in cys and gly back into process)
