functions of aa?
1. protein synthesis
2. energy production
3. synthesis of biochemicals
4. synthesis of purines, pyrimidines
5. synthesis of other compounds
what is glutathione? what is its structure?
the most abundant biochemical in most cells
most important cellular antioxidant, also imp in cellular redox control
is a tripeptide
functions in DNA synthesis and repair, protein synthesis, iron synthesis, prostaglandin synthesis, amino acid transport, enzyme activation
how is glutathione synthesized?
from glutamate, cysteine, and glycine:
1. glutamate + cysteine make gamma-glutamyl cysteine by enzyme gamma-glutamyl cysteine synthetase
rate limiting enzyme of the pathway
uses ATP -> ADP + Pi
2. glycine + ATP -> ADP + Pi via glutathione synthetase
makes GSH, glutathione
what is unique about interactions between glutamate and GSH?
gamma carboxyl group of glutamate makes the important bond w/ gamma-glutamyl-cysteine, rather than the alpha carboxyl group, which is unique
how does GSH function in cellular redox control?
maintains sulfhydryl-disulfide equilibrium:
2GSH + R-S-S-R' -> GSSG + RSH + R'SH
if GSH functions as an antioxidant, how does it change and how does it return to GSH?
GSH becomes GSSG
it is reduced back to GSH by glutathione reductase
is trytophan essential or nonessential aa?
what important molecules can tryptophan become?
1) niacin, which becomes NAD and NADP
2) serotonin, crucial neurotransmitter
3) melatonin, another important neurotransmitter
how is NAD / NADP generated?
tryptophan -> niacin -> NAD or NADP
how is serotonin made?
1. tryptophan hydroxylase
2. 5'hydroxy tryptophan decarboxylase reacitons
uses PLP as cofactor
what is serotonin
major neurotransmitter and major vasoconstrictor
important in blood pressure regulation, mood, depression
how is melatonin made
serotonin in made from tryptophan
serotonin is converted to melatonin in a 2 step pathway
1. acetyl CoA acetylates serotonin
uses THB -> DHB as cofactor
makes n-acetyl serotonin
2. N-acetyl serotonin acted on by SAM with PLP, Vit B12 as cofactors
what is melatonin
brain neurotransmitter important in regulating dark/light cycling so biological clock, appetite, mood
also an important antioxidant
what cofactors are used in tryptophan metabolism
PLP, THB, SAM, BH4 (Vit. B12)
waht aa does milk contain a lot of? effect?
what does tryptophan deficiency in diet cause?
metabolic disease, pellagra
associated w/ energy impairment, weakness, poor motor control, cardiovascular and neurological problems, death
how to treat pellagra?
give tryptophan or vitamin niacin in the diet
thus generate the NAD and NADP for so many metabolic pathways
what deficiency did people develop during the depression re: their diets
pellagra b/c of tryptophan deficiency b/c ate lots of corn for protein
how is trytophan metabolized in the brain?
by tryptophan hydroxylase, to 5-hydroxytryptophan
Tryptophan + O2 + THB -> 5'hydroxytryptophan + H2O + DHB
what are all the metabolic uses of THB as a cofactor?
THB: tetrahydrobiopterin (BH4)
important reductant cofactor for many pathways
1. phenylalanine -> tyrosine
2. make catecholamines
3. make serotonin, melatonin
what is creatine
an important cofactor
made of glycine, amidino group of arginine, and methyl group from arginine via SAM
describe creatine metabolism mechanism
1. glycine in the kidney + SAM + part of arginine form creatine in the liver
2. creatine undergoes creative phospho kinase, CPK, reaction, ATP->ADP. this is reversible!
produces creatine phosphate, a high energy compound
3. creatine pohsphate is stored in muscle, heart, and brain
4. creatine phosphate can break down to creatinine
creatinine is secreted in the urine, is indicative of kidney function, urine flow
what does CPK reaction produce
where is creatine P stored
muscle, heart, brain
how does creatine impact blood flow
when blood flow's impeded, so clots or stroke occurs, creatine P provides some ATP for energy if oxidative phosphorylation is impeded
what is creatinine
breakdown product of creatine P
secreted in the urine and its level in the urine is indicative of kidney function, urinary flow
how can CPK be used in diagnosis?
different isoforms of CPK exist in different tissue, so heart vs. muscle - if see elevation of heart CPK indicates heart attack, if see elevation of brain CPK indicates stroke
why is creatine phosphate important
it's a storage form of ATP
very important in energetics - when have heart attack or stroke, and tissue is deprived of ATP for any period of time >1 minute, damage occurs
describe glutamate decarboxylase reaction
glutamate can be decarboxylated by glutamate decarboxylase to form GABA, gamma-amino butyric acid, a major inhibitory neurotransmitter
action of histadine DC?
Histidine -> Histamine, a vasodilator
functions of histamine
present in individuals w/ inflammation and allergic attacks
also promotes secretion of pepsin and HCl
is important in protien digestion in the stomach
function of antihistamines
prevent the vasodilatory effects of too much histamine
what might an anti-ulcer drug target
histamine in the stomach
b/c histamine is important in digestion
anti-ulcer drugs are used to inhibit aciton of histamine in stomach, inhibit proteases
function of serine DC?
Serine -> EThanolamine
this is a major base in phospholipid phosphatidyl ethanolamine membrane structure
function of ornithine decarboxylase?
function of products?
Ornithine -> putrescine -> polyamines spermine and spermidine
these are nitrogenous bases that help to stabilize and bind to DNA, esp during DNA replication
what do decarboxylases use as their cofactor?
PLP, which is from B6
how is nitric oxide made
1 step from enzyme NO synthase:
arginine + NADPH + H+ -> citrulline + nitric oxide
citrulline enters urea cycle, goes back to arginine
THB is the reductant for the reaction and then NADPH
function of NO?
regulator of blood pressure and blood flow
prevents platelet aggregation
what is nitroglycerin
pill that releases nitric oxide when placed under the tongue
to reduce the pain and discomfort from heart attacks and poor blood flow
what function does NO have w/ bacteria
powerful anti-bacterial agent
reacts w/ heme-containing enzymes to block oxygen activate, eg cytochrome oxidase or cytochrome P450
however this also impacts mammalian enzymes
nitroc oxide function in brain
how does viagra work
contains nitric oxide
vasodilator and blood pressure increases