Lecture9-AMINOACIDMETABOLISMPART2 Flashcards
What are the fates of arginine?
Protein synthesis, nitric oxide, creatine, L-ornithine and agmatine
What is the precursor of ornithine in intestinal arginine metabolism ? taken place where?
Glutatmate
mitochondria
What two precurors of ornithine?
Glutamate (in mitochondrion) and arginine (in cytosol)
Citrulline comes from where?
Ornithine and carbamoyl phosphate (urea pathway)
What is the fate of citrulline? with what enzyme and other factor? ?
Fate: arginino-succinate
Enzyme and factor: Arginiosuccinate synthetase and aspartate
What is the fate of argininosuccinate?
Arginine to then go to ornithine
What is the nitric oxide synthase reaction?
Arginine to citrulline and NITRIC OXIDE with nitric oxide synthase (eNOS)
Also called citrulline NO cycle
**the e is for endothelial
What is NO?
It is a signaling molecule to allow relaxation in muscle
Where and when is arginiosuccine synthetase (AS) used?
LIVER: in the urea cycle, AS is used to take citrulline to argininosuccinate to then be later converted to UREA
*** get rid of NH4+
KIDNEY : AS is used to take citrulline to agininosuccinate to later be created to arginine
ENDOTHELIUM: in the citrulline-NO cycle, AS is used to take citrulline to argininosuccinate to later make NO
Arginine can turned to omithine with what enzyme and what is released (think urea cycle)?
Arginase and releases urea
In creatine biosynthesis what is the precursor of creatine?
arginine
Where is creatine created?
In the liver
What happens after the creation of creatine
In the muscles, creatine phosphate is created with the help of ATP and creatine phosphokinase
Now overall what are ALL the ‘products’ of arginine
Ornithine and urea
NO
creatine
Arginine can help with the formation of proline with glutamate
What is the precursor of glutamate
histidine
Glutamate can form what?
Proline
What can help glutamate to make proline
arginine
What is the precursor of tyrosine
phenylalanine
What are the fates of tyrosine
Thyroid hormones (thyroid)
Catecholamines (adrenals, CNS)
Melanine (e.g. skin)
Fumarate and acetoacetate (liver)
Example the whole phenylalanine hydroxyase reactions
7,8- dihydrobiopterin is reduced by dihydrobiopterin reductase (with NADH) to produce 5,6,7,8-tetrahydrobipterin (THIS IS THE COFACTOR)
5,6,7,8-tetrahydrobipterin and the enzyme phenylalanine hydroxylase (with O2) is used to take phenylalanine–>tyrosine
What happens when we do not have enough 5,6,7,8-tetrahydrobipterin
We will not convert phenylalanine–>tyrosine effectively
What is needed with dihydrobiopterin reductase?
NADH+H to go to NAD+
What is needed for Phenylalanine hydroxylase besides 5,6,7,8-tetrahydrobipterin?
Oxygen
A deficiency in Phenylalanine hydroxylase and dihydrobiopterin reductase causes what?
PKU
Which enzyme is deficient in TRADITIONAL PKU patients?
Phenylalanine hydroxylase
Which enzyme is deficient in ATYPICAL PKU patients?
dihydrobiopterin reductase
What is the solution to the enzyme deficiency in PKU patients ?
Saproterin=Kuvan which is an analog of 5,6,7,8-tetrahydrobipterin so it can bypass the cofactor and make tyrosine
avoid Phenylalanine which is in aspartame (sweetener) in soft drinks
What are symptoms in PKU patients?
Neurological issues
How does PKU cause neurotoxicity ?
Phenylalanine interfere with the hydrophobic amino acid transport across Blood brain barrier, COMPETING for the SAME active transport system as LEUCINE, component of MYELIN
Phenylpyruic acid is a competitive inhibitor of pyruvate dehydrogenase (PDH) complex, PDH complex is essential in synthesis of fatty acids and cholesterol thus an increase in phenylpyruvic acid contributes to lack of myelin formation
What is the precursor of tyrosine
Phenylalanine
What is the fate of tyrosine ?
dopamine, norepinephrine and epinephrine
What is the Rate limiting step of the formation of dop, nor, and epinephrine from tyrosine?
Tyrosine hydroxylase
More specific, what is the precursor of dopamine ? what enzyme?
DOPA
DOPA decarboxylase–> release CO2
What inhibits DOPA decarboxylase ?
carbidopa
What is another fate of tyrosine besides dope, nore, epi?
Pheomelanine (red pigments) and eumelanins (black pigments)
Thyroid hormones
what is the enzyme used to make pigments? what happens if we inhibit this ?
tyrosinase (cu+2)
Albinism
What is the precursor of thyroid hormones
tyrosine
NOW, what are ALL THE FATES FOR TYROSINE
thyroid hormones
Pheomelanine (red pigments) and eumelanins (black pigments)
DOPA to dopamine, norepinephrine, epinephrine
What is the fate of tryptophan
Serotonin, Nicotinate (niacin), Melatonin
Indoleacetate (not highlighted on her slide)
What is the rate limiting step used to take tryptophan to serotonin
Tryptophan 5-hydroxylase
Serotonin is a neurotransmitter that is responsible for what?
responsible for exerting inhibitory control over impulsive behavior
besides tryptophan what can help form melatonin? (lower yield)
serotonin
What is the fate of nicotinate (niacin)? lower yield
NAD and NADP
In a different slide, she used stated another precursor (besides serotonin) is what?
5-hydroxytryptophan
Just in case she does not use serotonin, what is the chemical name of serotonin?
5-hydroxytrptamine
