where does non-essential aa synthesis occur?
in the cytosol of all tissues
anabolic synthesis of glutamate?
Glutamate Dehydrogenase Reaction:
aKG + NH3 + NADH Glutamate + NAD+
used in urea cycle
anabolic synthesis of glutamine?
Glutamine Synthase Rxn:
Glutamate + ATP + NH3 -> Glutamine + ADP + Pi
used in urea cycle to transfer ammonia from muscle & other tissue to liver
anabolic synthesis of aspartate?
GOT transamination reaction:
Glutamate + OAA aKG + Aspartate
these are TCA cycle intermediates
asparagine anabolic synthesis?
Asparagine synthase rxn:
Aspartate + Glutamine + ATP -> Asparagine + Glutamate + ADP + Pi
Alanine anabolic synthesis rxn?
GPT or Ala aminotransferase rxn:
Pyruvate + glutamate Alanine + a-KG
what is the alanine:glucose cycle?
when exercising muscle uses lots of glucose & therefore produces lots of pyruvate, exceeds the capacity of the PDH and LDH reactions
excess pyruvate -> alanine by the Muscle GPT reaction
alanine leaves mucle, circulates to liver, where -> pyruvate by Liver GPT
Pyruvate -> gluconeogenesis
Glucose is secreted from liver, -> muscle to be used for energy via glycolysis
what non-essential aa is found in high levels in the blood during exercise?
alanine, traveling to liver to undergo liver GPT reaction to become pyruvate and undergo gluconeogenesis there in liver
proline anabolic synthesis rxn?
glutamate -> gamma-glutamic semi-aldehyde -> proline
gamma glutamic semi-aldehyde can -> ornithine, thus it is a precursor to either proline or ornithine
arginine anabolic synthesis rxn?
glutamate -> ornithine, which reacts w/ Carbamyl P + Aspartate -> Urea Cycle -> Arginine
is arginine an essential aa?
in adults, no - they get enough from glutamate, carbamyl P, and aspartate
in children or growth/development, yes - do not get enough arginine in this pathway to sustain maximal development
rxn for anabolic synthesis of cysteine?
Methionine + Serine via Cystathionine
in Transsulfuration pathway
Methionine provides the S, Serine provides all over atoms
Methione is from homocysteine
Serine is from cystathione
is cysteine essential or non essential?
NON-ESSENTIAL as long as methionine is in excess
how is tyrosine anabolically synthesized?
phenylalanine hydroxylase rxn:
Phenylalanine - O2, thb, Phe, OH -> tyrosine + dhb + H2O
is tyrsoine nonessential or essential?
nonessential as long as there's sufficient phenylalanine in diet
anabolic synthesis rxn for serine?
1. From glycolysis intermediate:
3PG -> -> Serine
Serine transhydroxymethylase reaction:
Glycine + N5N10CH2THF Serine + THF
is serine an essential or nonessential aa?
non-essential as long as either:
1. glucose is being metabolized to 3PG or glycine and
2. a C atom from folate pool is available
glycine anabolic synthesis rxn?
1. From serine:
Serine + THF Glycine + N5N10CH2THF
2. De novo:
CO2 + NH3 + N5N10CH2THF + NADH -> Glycine + THF + NAD+
what is the #1 donor of C atoms into the folate pool?
where does glycine reaction's methylene come from?
histidine or another serine
why can benzoat be used as a treamtn for ammonia intoxication?
when add benzoic acid to reaction, it reacts w/ glycine; ammonia gets incorporated into glycine, which then conjugates w/ benzoate
this forms the soluble hippuric acid
hippuric acid is excreted, and so is ammonia
what are catecholamines?
where are they synthesized?
DOPA, Dopamine, Norepinephrine, Epinephrine
synthesized in: brain and adrenals
function: neurotransmitters, regulators of blood flow, blood pressure, metabolism, energy production
pathway of catecholamine synthesis?
1. tyrosine hydroxylase rxn converts tyrosine -> DOPA; uses THB, O2 as cofactors
rate limiting enzyme
2. DOPA -> Dopamine + CO2 by Dopa decarboxylase, sues PLP as cofactor
3. Dopamine -> Norepinephrine by Dopamine B-hydroxylase, uses Vitamin C (Ascorbate)
4. Norepinephrine -> Epinephrine by Phenylethanolamine N-methyl transferase, uses SAM
function of DOPA?
mostly to synthesize dopamine, norepinephrine, epinephrine
critical neurotransmitter, helps control coordination, motor control, mood
what does dopamine deficiency cause?
deficiency in substantia nigra of brain -> Parkinson's disease
oxidizes monoamines - neurotransmitters like Dopamine, Norepinephrine, Epinephrine - removes them, produces H2O2 in producess
so brains are subject to H2O2 production all the time
espeically occurs in substantia nigra of brain - and H2O2 presence prevents production of Dopamine in this region of brain
treatment for Parkinson's?
provide DOPA, which can cross blood-brain barrier, rather than Dopamine, which is positively charged at physiologic pH and cannot cross blood-brain barrier
in the substantia nigra, Dopa -> Dopamine
eventually, treatment stops working b/c resistance to Dopa develops
function of norepinephrine?
critical for maintaining blood flow, blood pressure
which 2 non essential aa become essential if their precursor aa isn't present
Cysteine and Tyrosine
which 2 non essential AA can be formed in 1 step by direct trasnamination
what key role does foalte play in interconversion between serine and glycine
provides the exstra C atom needed for serineglycine
what are catecholamines? what are their functions?
chemicals – DOPA, Dopamine, Norepinephrine, Epinephrine –produced from Tyrsosine, synthesized in the brain and adrenals, that function as neurotransmitters and controllers of blood flow, blood pressure, metabolism, and energy production
what is major problem in individuals w/ parkinson's disease?
what catecholamine is used for treatment?
Individuals with Parkinson’s have a deficiency in the catecholamine Dopamine in the substantia nigra of the brain because of the action of Monoamine Oxidase, which oxidizes Dopamine and produces H2O2 which, in abdunace in the substantia nigra, prevents Dopamine synthesis.
DOPA is used for treatment because it can cross the blood-brain barrier and become DOPAMINE, whereas DOPAMINE itself cannot cross the blood-brain barrier
what cofactor is used in each of the 3 stepf of tyrosine -> norepinephrine conversion?
1. Tyrosine hydroxylase- THB + O2
2. DOPA Decarboxylase- PLP
3. Dopamine B-hydroxylase- Vitamin C (ascorbate)