Lecture - Biochemical Synthesis 1 Flashcards
Key biochemical species
- amino acids
- fatty acids
NEcesary precursors
- Purines
- Pyrimidines
- Ribose
- Cholesterol
- Porphyrins
Energy rich compounds for storage or export
- Fatty acids
- Ketone bodies
Providion of reducing power
- NADH
- NADPH
- Glutathione
DEtoxification and excretion
- Urea
- Mono-oxygenases
- glucuronidation
Biochemical species that cannot be synthesized
- Vitamins (except vit D)
- Essential amino acids
- essential fatty acids
Essential and non-essential amino acid
- Essential aa: required in diet, cannot be synthesized
- non essential aa: not required in fiet, synthezised from ingested precursors
Essential amino acids
- lysine
- histidine
- threonine
- methionine
- Phenylalanine
- Tryptophan
- Isoleucine, Leucine, Valine
Non essential amino acid
- Arginine
- Aspartate
- Glutamate
- Asparagine
- Glutamine
- Alanine
- GLycine
- Serine
- Cysteine
- Proline
- Tyrosine
Conversion of L-phenylalanine to L-tyrosine
- requires phenylalanine hydroxylase
- requires vitamine B
Synthesis of neurotransmitters from L-tyrosine
- tyrosine hydroxylase
- dopa decarboxylase
- dopamine b-hydroxyklase
- PNMT
- forms dopa then dopamine then norepinephrine and then epinephrine
Example of aa synthesis : Glutamate
- Glutamate can form a-ketoglutarate via the glutamate dehydrogenase enzyme
- glutamate is a precursor for several other AA: Glutamine, Proline, Arginine
Synthesis of FA: two important carriers
- coenzyme A
- Acyl carrier protein (ACP)
Synthesis of FA: the committed step
- when acetyl coA becomes malonyl co A (2C -> 3C)
- acetyl coA receives a carbon dioxide froup from bicabonate
Synthesis of FA: fatty acid dynthase complex
After malonyl coA, becomes condensed into 1C
- then a bunch of reductions forms butyryl ACP
- after butyryl ACP is formed, chain length increases by two carbons each cycle
- maximum chain length via Fatty acid synthase complex is 16C
3 ways to nomenclature fatty acid
- numbering from COOH: 1
- numbering from carbon after COOH: a,b,y,w
- Numbering from last carbon: w1, w-2…
Synthesis of longer chain FA and desaturation
- some very long chain FA required for membrane function
- desaturation: insertion of double bonds
- enzymes on cytoplasmic face of ER facilitate elongation and desaturation reaction
Cis vs trans fatty acid
CIS
- kinked
- natural form and major configuration in natuyre
- can synthesize ourselves, melting temp drops - more liquid
TRANS
- not kinked
- possible to make synthetically
- tend to pack and crystallize early
Essential fatty acids
- unsaturated FA with double bond beyoung C9
- desaturating enzymes cannot process this far from C1
- some essential fatty acids are required for synthesis of important biochemicals
N6- can be obtained in a wide variety of food
N3- more limited
Synthesis of cholesterol
- Acetyl coA -> Aetoacetyl coA -> HMG CoA -> Mevalonate
- statins inhibit HMG CoA to mevalonate : lower cholesterol but secondary effect include enhanced clearance of cholesterol rich lipoproteins
- Mevalonate -> C5 -> C10 -> C15 -> C30 (sqalene) -> C27 (cholesterol)
Synthesis of C10 and C15 is suppressed by biphosphonates
- but C15 is needed for protein prenylation (Ras) and Heme A (coenzyme Q10)
What is synthesized from cholesterol?
- steroids
- bile salts