Block 3 Flashcards
how does a nucleoside differ from a nucleotide
nucleoside- sugar+base
nucleotide- sugar+base+phosphate
where are new nucleotides made
liver cytoplasm
how are new nucleotides transported
by RBC
what is the starting molecule for nucleotide synthesis
ribose 5-phosphate
how does purine synthesis differ from pyrimidine synthesis
purine- create base then add sugar
pyrimidine- make sugar then build base
what is the first step of purine synthesis
addition of 2 phosphates from ATP to ribose 5-phosphate to make PRPP (phospho ribosyl pyro phosphate)
what enzyme catalyzes the first step of purine synthesis, adding 2 phosphates from ATP to ribose 5-phosphate
PRPP synthetase (phospho ribosyl pyro phosphate
PRPP synthetase in purine synthesis is inhibited by what molecules
GDP and ADP
what enzyme is involved in the second step of purine synthesis, adding amine from glutamine to PPRP
phosphoribosyl amido transferase
what is glutamine phosphoribosyl amino transferase (PRAT) of purine synthesis inhibited by
IMP, GxP, AxP
allopurinol is an indirect target of __ but a direct target of __
indirect- PRAT
direct- xanthine oxidase
what 3 amino acids are involved in purine production
glycine, glutamine, asparatate
how does methotrexate act as an anticancer drug
inhibits DHFR and tetrahydrofolate production, preventing addition of carbons to the purine ring, inhibiting cell growth
in purine synthesis, what is the common molecule before the branchpoint into ATP and GTP
IMP
what enzyme converts IMP to GMP
IMP dehydrogenase
what reversibly inhibits IMP dehydrogenase, inhibiting IMP to GMP
mycophenolic acid
IMP+___= AMP
asparatate
IMP+___= GMP
glutamine
what are the 2 products of the purine nucleotide cycle
NH3 (to urea cycle)
fumarate (to TCA cycle)
what accounts for maintaining balance between AMP and GMP production
IMP+GTP+aspartate= AMP
IMP+ATP+glutamine= GMP
*production of one type of nucleotide requires the other type as an energy source
what does adenylosuccinate synthetase of purine synthesis do
makes AMP from IMP
what is adenylosuccinate synthetase inhibited by
AMP
what does IMP dehydrogenase of purine synthesis do
make GMP from IMP
what is IMP dehydrogenase of purine synthesis inhibited by
GMP
regulation of purine production in liver cells is inhibited by ___
high levels of ATP and GTP
for DNA synthesis, we need ___ nucleotides
deoxy-ribose
what enzyme converts nucleotides to deoxynucleotide which are needed for DNA synthesis
ribonucleotide reductase
what activates ribonucleotide reductase, the enzyme needed to convert nucleotides to deoxynucleotides
what inhibits it
ATP
dATP (deoxyATP)
what is an alternative way to make purines, instead of synthesis in liver cells
salvage them from the diet
AMP is degraded to __
GMP is degraded to __
hypoxanthine
guanine
*both are released into blood
if ingested nucleotides are not salvaged from the diet and converted to nucleosides, they are converted to __
uric acid
since uric acid is not very water soluble, it is released into the blood and forms __
crystal
excessive uric acid in the blood can lead to __
gout
what is the effect of allopurinol inhibiting xanthine oxidase
decreased uric acid, buildup of hypoxanthine= increased A and G= inhibit purine synthesis
what is the effect of APRT (adenosine phosphoribosyl transferase) deficiency
increase adenosine= increased crystallization= increased kidney/urinary stones
what is the effect of adenosine deaminase deficiency
deficiency of B and T cells= SCIDS (severe combined immunodeficiency)
causes pyrimidine starvation
what is the effect of HGPRT (hypoxanthine guanine phosphoribosyltransferase) deficiency
guanine isn’t converted to GMP+IMP= no guanine recycling= 100% excretion as uric acid= Lesch-Nyhan disease
what are the 3 starting molecules for pyrimidine synthesis
glutamine, CO2, ATP
the first step of pyrimidine synthesis which converts glutamine to carbamoyl phosphate is achieved by what enzyme
carbamoyl phosphate synthetase II
carbamoyl phosphate + ____ –>orotate (orotic acid)
aspartate
orotate is converted to UMP through the addition of __
PRPP
what is the result of deficiency of the enzyme that converts orotate to UMP in pyrimidine synthesis
orotic aciduria
in pyrimidine synthesis, UDP can be converted to __ or __
UTP
dUDP
in pyrimidine synthesis, UTP is converted to CTP through the addition of what amino acid
glutamine
dUMP is converted to dTMP by what enzyme in pyrimidine synthesis
thymidylate synthase
what enzyme converts UDP to dUDP in pyrimidine synthesis
ribonucleotide reductase
what molecule is needed to convert dUMP to dTMP in pyrimidine synthesis
folate
FH2–>FH4 for dUMP–>dTMP in pyrimidine synthesis involves what enzyme
dihydrofolate reductase (DHFR)
what amino acids contribute CH3 needed for folate synthesis
serine or glycine
the nitrogen atoms of a pyrimidine ring come from what 2 amino acids
glutamine
aspartate
methotrexate targets what enzyme
dihydrofolate reductase
5-fluro-uracil targets what enzyme of pyrimidine synthesis
thymidylate synthase
ribonucleotide reductase is targeted by what anti-cancer drug
hydroxyurea
carbamoyl phosphate synthase II of pyrimidine synthesis is activated by ___
PRPP
carbamoyl phosphate synthase II of pyrimidine synthesis is inhibited by ___
UTP
orotic aciduria can be caused by OTC deficiency in the uric acid pathway or by pyrimidine synthesis malfunction. how do you differentiate which it was caused by
high orotic acid+normal N= pyrimidine synthesis malfunction
high orotic acid+low N= OTC deficiency
what are 8 peptide hormones that use Gs of GPCR
Angiotensin II
FSH
LH
ACTH
TSH
Catecholamines (beta receptors)
ADH (vasopressin II)
PTH
what are 4 peptide hormones that use Gq of GPCR
vasopressin I
oxytocin
catecholamines (alpha-1 receptor)
angiotensin II
what are 2 peptide hormones that use RTK/MAP kinase pathway
insulin
insulin-like growth factor (IGF-1)
what are 3 peptide hormones that use RTK/JAK-STAT pathway
growth hormone
prolactin
cytokines
what are 2 peptide hormones that use guanyl cyclase pathway
brain natriuretic peptide (BNP)
atrial natriuretic peptide (ANP)
NO also uses this pathway
steroids use what receptor type
intracellular cytoplasmic
thyroid hormone, vitamin A, vitamin D, and fatty acids use what receptor type
intracellular nuclear
Cholera toxin is a ___ activator
cAMP
pertussis toxin is a ___ activator
PKA
how does cholera toxin work
locks Gs in its GTP form, keeping Cl- channels open (efflux of Cl/Na/H2O)
how does pertussis toxin work
inhibits activity of Gi, keeping PKA active
how do antihypertensive drugs work
increase cGMP, leading to vasodilation
where are steroid hormones synthesized
mitochondria/SER
what are the 5 releasing hormones released by the hypothalamus
TRH
CRH
GnRH
GHRH
MS-RH (melanocyte stimulating release hormone)
what are the 3 inhibitory hormones released by the hypothalamus
GHIH (somatostatin)
dopamine
MIH
what is the difference between tropic and nontropic hormones
tropic- stimulate other glands to secreter hormones
nontropic- directly affect the target cell
what are the 4 tropic hormones released by the anterior pituitary
ACTH
TSH
LH
FSH
what are the 3 nontropic hormones released by the anterior pituitary
GH
MSH
prolactin
growth hormone increases __ utilization and __ synthesis, and decreases __ utilization
fat utilization
protein synthesis
carbohydrate utilization
what are the 2 hormones released by the posterior pituitary
oxytocin
ADH
what is the main function of ADH
reabsorb H2O from urine
besides water balance, ADH also functions to maintain __
blood pressure through vasoconstriction
neurogenic/central diabetes insipidus occurs due to __, while nephrogenic diabetes insipidus occurs due to __
neurogenic/central= decrease in ADH secretion–>high plasma osmolarity
nephrogenic= defective ADH receptors–>high plasma osmolarity
is T3 or T4 metabolically active
T3
is T4 converted to T3, or is T3 converted to T4
T4–>T3
does thyroid hormone increase or decrease lipolysis
increase
thyroid hormone upregulates metabolism of what
carbs
fats
proteins
what enzymes convert free T4–>active and inactive T3
deiodinases
what causes gigantism
increase in GH prior to adolescence
what is the effect of gigantism
increase in longitudinal bone growth
hyperglycemia
what causes acromegaly
an increase in GH and IGF after puberty
what is the effect of acromegaly
large gaping teeth
large hands/feet
kyphosis
transverse bone growth
what causes African pygmies or Levi Lorain dwarves
defective GH receptor–>deficiency in IGF-1
what causes diabetes insipidus
Decreased ADH production–>high plasma osmolarity/dilute urine
In diabetes insipidus, the lack of production of ADH means the kidneys cannot make enough concentrated urine and too much water is passed from the body
what are the symptoms of neurogenic/central diabetes insipidus
excessive thirst
dilute urine
hypotension
what is the result of neurogenic/central diabetes insipidus in terms of ADH
decrease in ADH secretion
what causes neurogenic diabetes insipidus
decreased ADH secretion due to decreased osmoreceptor function
syndrome of inappropriate ADH is causes by an increase or decrease in ADH secretion
increase
what are the symptoms of syndrome of inappropriate ADH
edema
vasoconstriction
hypertension
congestive heart failure
primary hypothyroidism results from __
loss of thyroid tissue
what is the effect of primary hypothyroidism
low T3/T4
high TSH
high TRH
secondary hypothyroidism results from __
reduced TSH secretion from the anterior pituitary
what is the effect of secondary hypothyroidism
low T3/T4
low TSH
high TRH
tertiary hypothyroidism results from __
low TRH from the hypothalamus
what is the effect of tertiary hypothyroidism
low T3/T4
low TSH
low TRH
what is myxedema
severe hypothyroidism
what are the symptoms of myxedema
painless goiter
hypoxia
hypoventilation
fluid/electrolyte inbalance
hypothermia
shock/death
what is Hashimoto’s thyroiditis
autoimmune disorder with loss of thyroid tissue due to anti-thyroperoxidase antibodies
congenital thyroid insufficiency is hypothyroidism in infants that can result from absence leading to __ and __ or low thyroid leading to __
absence–>hypotonia–>floppy baby syndrome
low thyroid–>dwarfism/mental disability
what causes cretinism seen in children
lack of dietary iodine–>decreased T3/T3–> increased TSH
what are the symptoms of cretinism
goiter
enlarged longue
reduced skeletal growth
what causes endemic colloid goiter
lack of dietary iodine in adults–>decreased T4/T3–>high TSH
hyperthyroidism leads to hyper__ and hypo__
hyperlipidemia
hypocholesterolemia
what is Grave’s disease
hyperthyroidism
the patient’s immune system makes a thyroid-stimulating immunoglobulin (TSI) antibody that attaches to the thyroid cells. TSI acts like thyroid-stimulating hormone (TSH), causing the thyroid to make too much thyroid hormone
what are the symptoms of Grave’s disease
bilateral exopthalmos
orange peel skin
non-pitting pretibial myxedema
goiter
what is the effect of multinodular toxic goiter
malignant thyroid nodules overproducing T3/T4
what is the difference between a hot and cold nodule produced with goiters
hot= can trap iodine
cold= can’t trap iodine
what causes goiters
increased TSH receptor stimulation
hyperthyroidism causes a __ in serum glucose
hypothyroidism causes a __ in serum glucose
hyper= increase
hypo= decrease
each gram of fat contains how many calories
9
each gram of carbohydrate contains how many calories
4
each gram of protein contains how many calories
4
what are the building blocks of muscle mass
protein
when do we have a positive nitrogen balance
when demands of protein are high
ex: growing children
pregnancy
recovery from illness
body building
when do we have a negative nitrogen balance
when nitrogen (protein) output is greater than nitrogen (protein) intake
ex: burns
trauma
illness
starvation
poorly controlled diabetes mellitus
surgery
cancer
___ are the favored energy source for burn patients
carbohydrates
why are carbohydrates (glucose) the favored energy source for burn patients
carbs promote wound healing and impart a protein sparing effect
what does it mean in saying carbohydrates promote a protein sparing effect
proteins are spared from gluconeogenesis in order to help rebuild muscle
following a burn, intravenous infusions of what increase nitrogen balance and muscle growth
glucose+amino acids (protein)
what state upregulates ubiquitin dependent proteolysis
starvation
what 3 things are given to a burn patient through IV
protein
glucose(can also say carbs) to spare proteins from gluconeogenesis towards muscle building
insulin (maintains blood sugar)
what nonenergy-dependent degradative enzymes perform protein degradation in the lysosomes
acid hydrolases
after proteosome activity, proteolysis occurs to break peptide fragments to amino acids. once the amino group is removed, what remains is called the ___
carbon skeleton
impairment of the ubiquitin-proteasome system can contribute to the development of what 2 neurogenerative disorders
Parkinson’s
Alzheimer’s disease
mutation in what 3 genes is associated with Parkinson’s disease
Parkin
PINK1
DJ-1
the first point of breakdown of exogenous proteins occurs where, by what enzyme
stomach with pepsin+HCl
what is the function of HCl in the stomach in regards to protein degradation
allows for activity of pepsin to denature proteins to their primary structure (breaks H binds, not peptide), allowing for a more linear structure for proteases to act on
what are zymogens
inactive forms of an enzyme
what makes zymogens inactive
they contain an extra amino acid in their sequence, preventing proper folding, therefore making them inactive
what allows for a zymogen to become active
removal of amino acids to permit for proper protein folding
what suffix indicates a zymogen
-ogen
where in the protein structure does pepsin hydrolyze proteins
bonds adjacent to aromatic amino acid residues (phenylalanine, tyrosine, tryptophan)
the next enzyme to act on proteins after pepsin activity is __ in the __
trypsin
small intestine
where in the protein structure does trypsin hydrolyze proteins
bonds adjacent to arginine or lysine (basic amino acids)
the release and activation of pancreatic zymogens is mediated by the secretion of __ by __ cells of the ___ in response to ___
cholecystokinin
I cells
duodenum and jejunum
ingestion of AA and FA
the final step of protein degradation is the release of free AA and smaller peptides due to the activity of what enzyme located in the luminal surface of the intestine
aminopeptidase
what allows for the uptake of free amino acids in the enterocytes
Na+ linked secondary transport
dipeptides and tripeptides can cross the luminal surface into the intestinal cell, however on __ can cross into the blood
amino acids
cystinuria is a genetic disorder that affects the transmembrane transport of what amino acids
basic
cysteine
ornithine
arginine
lysine
cystinuria is due to a defect in what type of amino acid absorption
absorption of basic amino acids
what is the main amino acid that causes cystinuria
cysteine
since basic amino acids aren’t easily absorbed from proximal convoluted tubule, they can accumulate and lead to ___
calculi (kidney stones)
what causes nephrolithiasis in regards to protein/AA transport
increase in cysteine due to the inability to be absorbed leads to recurrent stones in urine
what are 3 main symptoms of cystinuria
flank pain
hematuria
stones
Hartnup disease is caused by impaired transport of what amino acids
neutral, especially tryptophan
Hartnup disease is caused by impaired transport of tryptophan in what 2 body sites
small intestine
proximal convoluted tubule of kidney
tryptophan can be converted into what 3 molecules
melatonin
serotonin
niacin
pellagra is a condition similar to Hartnup disease based on presentation and cause. how can they be differentiated
pellagra does not cause a buildup of tryptophan in the urine
hartnup disease causes an increase in tryptophan (neutral amino acids) to be excreted in urine due to impairment of it’s reabsorption transporter
what are the 4 main symptoms of Hartnup disease
pellagra-like rash
neurological symptoms (dementia)
diarrhea
neutral aminoaciduria
what is the treatment of Hartnup disease
high protein diet with daily niacin (high protein diet/tryptophan rich diet with neutral AA+niacin)
in amino acid degradation, the amino group is used in what process
urea cycle
in amino acid degradation, the carbon skeleton is used for __ and __
gluconeogenesis
oxidation in Krebs cycle
what is the first step in AA degradation
removal of nitrogen (amino group)
alpha-keto… means it is an amino acid without what group
NH3
what occurs in transamination
transfer of -NH3 from one amino acid to another
most excess nitrogen is converted to __ in the __
urea
liver
before being excreted, excess nitrogen is converted to urea in the liver and through the blood to the ___
kidneys
what enzyme removes -NH3 from amino acids
aminotransferases
aminotransferases, which transfer the -NH3 group of an amino acid, use what as a coenzyme
B6 (pyridoxal phosphate)
in amino acid breakdown, the effect of transamination reactions is to collect the amino groups from different amino acids in the form of _____
L-glutamate
in __, glutamate is transported from the cytosol into the mitochondria where it undergoes oxidative deamination
hepatocytes
what enzyme performes oxidative deamination in AA degradation
L-glutamate dehydrogenase
where is L-glutamate dehydrogenase found
hepatocyte mitochondrial matrix
what is the only enzyme that can use either NAD+ or NADP+
L-glutamate dehydrogenase
the common collector amino acid for -NH3 everywhere is __
the common collector amino acid for -NH3 in muscle is ___
everywhere= glutamate
muscle= alanine
the Cori cycle is used for what 2 processes
gluconeogenesis
AA salvage
the common collector amino acid for NH3 is ___
glutamate
what amino acid transports NH3 in cases of hyperammonemia
glutamine
what pair of enzymes is involved in detoxifying/capturing/deaminating ammonia
glutamate dehydrogenase
glutamine synthetase
what enzyme protects neurons from ammonia toxicity
glutamine synthase
elevated ammonia during hyperammonemia has the most toxic effects on what organ
brain
what are the 2 main functions of glutamine
protection from hyperammonemia
maintain acid/base balance through the kidney bicarbonate buffer system
under acidic conditions, the liver diverts glutamine to the __ in order to maintain the pH of blood
kidneys
during metabolic acidosis, H+ combines with NH3 to form __ which is ultimately excreted in the urine
NH4+
ammoniagenesis involves formation of what
glutamine
what enzyme is found in the kidneys that allows it to deaminate glutamine to produce NH3+ and glutamate
glutaminase
what induces the action of glutaminase in the kidney
chronic acidosis
altered levels of AST and ALT indicate disfunction of what organ
liver
what is the main end product of protein (nitrogen) catabolism
urea (blood urea nitogen)
what is the main end product of purine catabolism
uric acid (urate)
what is the main end product of heme catabolism
bilirubin
what is the function of the urea cycle
convert toxic nitrogen to urea for excretion in the kidneys
the first 2 reactions of the urea cycle occur in the ___, while the rest of the steps occur in the ___
mitochondrial
cytosol
carbamoyl phosphate synthetase I is involved in ___, while carbamoyl phosphate synthetase II is involved in __
urea
pyrimidine
carbamoyl phosphate synthetase I is found in ___, while carbamoyl transferase II is found in __
I= mitochondrial matrix
II= cytosol
transport of ornithine into the mitochondria and citrulline out into the cytosol is performed by what mechanism
antiporter
the urea cycles requires the input of how many ATP molecules
3
urea is composed of how many nitrogen
2
where do the 2 nitrogen of urea come from
1 from free NH3 that was captured
1 from aspartate
what acts as an additional activator of N-acetylglutamate in the urea cycle
arginine
what molecule acts as an allosteric activator of carbamoyl phosphate synthetase I
N-acetylglutamate
what is the rate limiting enzyme of the urea cycle
carbamoyl phosphate synthetase I
what activates carbamoyl phosphate synthetase I of the urea cycle
N-acetylglutamate (NAG)
what are the 2 main symptoms of hyperammonemia
flopping tremors (asterixis)
cerebral edema
what enzyme is deficient in congenital hyperammonemia type I
carbamoyl phosphate synthetase 1
what are the 3 symptoms of carbamoyl phosphate synthetase I
increase NH3
decreased BUN (urea)
increased glutamine
what enzyme is deficient in congenital hyperammonemia type II
ornithine transcarbamoylase (OTC)
what are the lab findings of ornithine transcarbamoylase deficiency
increased carbamoyl phosphate
orotic aciduria
what enzyme is deficient in citrullinemia
arginosuccinate synthase
what enzyme is deficient in arginosuccinic aciduria
arginosuccinase
what enzyme is deficient in hyperargininemia
arginase
what are the 3 main reasons why ammonia is toxic
glutamine is osmotically active= cerebral swelling
decrease in glutamate= decrease in neurotransmitters
inhibition of TCA cycle reduced production of ATP by brain
what is the main first line treatment for urea cycle disorders
protein restriction
how does lactulose help treat hepatic encephalopathy
it acts in GIT to capture NH3+ to make it insoluble to NH4, allowing for excretion in stool
how does lactulose help treat hepatic encephalopathy
it acts in GIT to capture NH3+ to make it insoluble to NH4, allowing for excretion in stool
what is phenylbutyrate used in treatment of
hyperammonemia
how does phenylbutyrate used for hyperammonemia work
it decreases the osmotic effect on the brain and allows for N secretion in the urine
hyperammonemia can be acquired through disease/failure of what 2 organs
liver (NH3 formation site) or kidneys (NH# secretion site)
how is it that recent GI bleeding causes an increase in nitrogen absorption in the gut
blood protein breaks down into amino acids which further break down in to NH3+ and C skeleton
the NH3+ typically is converted to urea, however with hepatic disease, the NH3+ is not converted to urea
what are the 2 ketogentic AA
leucine and lysine
what enzyme deficiency causes type I hyperprolinemia
proline dehydrogenase
what enzyme deficient causes type II hyperprolinemia
glutamate gamma semialdehyde dehydrogenase
what symptom does a deficiency in an arginine catabolism enzyme lead to
atrophy of retina
what 7 amino acids enter the TCA cycle as acetyl CoA
tryptophan
lysine
phenylalanine
tyrosine
leucine
isoleucine
threonine
what amino acid loading is used to diagnose a deficiency in vit B6
tryptophan
what enzyme of tryptophan catabolism requires vit B6
kynureninase
when there is a deficiency in vit B6, tryptophan does not broken down to enter the TCA cycle. Instead, what does it form
xanthurenate
before phenylalanine is converted to fumarate (an intermediate of the TCA cycle), what amino acid does it form
tyrosine
what enzyme is deficient in phenylketonuria (PKU)
phenylalanine hydroxylase
phenylalanine is toxic to what organ
brain
what are the symptoms of phenylketonuria
musty body and urine odor
phenylketonuria results in an elevated concentration of what
phenylalanine
the musty odor that occurs in phenylketouria results from production of what
phenylpyruvic acid
the production of melanin produced by tyrosine through tyrosinase is inhibited by what
phenylketouria (excess phenylalanine)
what are the symptoms of phenylketouria
hypopigmentation of external and internal features (basal ganglie, substantia nigra, locus ceruleus)
seizures
musty body and urine odor
what are 2 screening/diagnosis methods for phenylketouria
enzyme function test
blood/urine phenylalanine test 24-48 hours after birth
what is the treatment for phenylketouria
restriction of phenylalanine diet
supplementation of tyrosine
if standard treatment for phenylketouria does not work, it may be suspected that there is a deficiency in what enzyme
dihydrobiopterin reductase
what are the lab findings of dihydrobiopterin reductase deficiency
high phenylalanine
low dopamine (leads to neurological deterioration)
high prolactin
is phenylalanine crossing the placenta beneficial to the fetus
no, phenylalanine acts as a teratogen
what is the effect of children born to mothers with untreated phenylketouria
they have symptoms of PKU even through they may be heterozygous for the PKU gene
what enzyme deficiency causes alkaptouria
homogentisate oxidase
what is the main symptom of alkaptoura
urine turns a dark brown/black color when exposed to air
in alkaptorura, what is produced in large amounts that is excreted, allowing for the production of dark urine when exposed to air
homogentisate (alkapton)
what are the symptoms of alkaptourina that are seen late in the disease
arthritis
black tissue pigmentation (ochronosis)
since urine has to be exposed to air for appoximately 2 hours before turning black to diagnose alkaptouria, what may be added to the urine to speed up the reaction
ferric chloride
in methionine salvage, what are used as cofactors
B12
folate
in methionine breakdown, what is used as a cofactor
vit B6
what is the function of vit B12 in regards to folate
B12 activates folate to THF for use in our cells
in methionine recycling, what molecule acts as a methyl group donor
s-adenosyl methionine (SAM)
deficiency in what enzyme causes homocystinuria
cystathionine synthase
what accumulates with cystathionine synthase deficiency (homocystinuria)
homocysteine
methionine
what is the treatment for homocystinuia
remove methionine and homocysteine from the diet
supplement cysteine and B6
what are the 3 presentations of homocystinuria
marfanoid habitus
lens subluxation
thromboembolic events
marfans can present similar to homocystinuria, however __ presents at a younger age, __ patients eyes point downwards and inward, and __ presents with hyperextensible joints
homocystinuria= younger age
homocystinuria= downward and inward
marfan= hyperextensible joints
what is the treatment for homocystinuria
increase vit B6 and cysteine
restrict methionine
branched chain amino acids (leucine, isoleucine, and valine) use what enzyme complex
branched chain alpha-keto acid dehydrogenase complex
maple syrup disease is a deficiency in what enzyme
alpha-keto acid dehydrogenase complex
what causes maple syrup disease
the branched chain amino acids are not broken down so they are increased in the urine
what are the symptoms of maple syrup urine disease
sweet, burnt smelling urine
in maple syrup urine disease, what is used as a cofactor
vit B1 (thiamine)
what 2 amino acids enter the TCA cycle as fumarate
phenylalanine
tyrosine
leucine enters the TCA cycle as what
acetyl CoA
threonine, methionine, valine, and isoleucine enter the TCA cycle as __
succinyl CoA
propionic acid is converted to methylmalonic acid by what process
biotin dependent carboxylation
methylmalonyl CoA goes through what process to form succinyl CoA
isomerization
propionic acidemia is caused by a deficiency in what enzyme
propionyl CoA carboxylase
what occurs in the absence of propionic acid or methylmalonyl CoA
metabolic acidosis
what diet is needed for a patient with propionic acidemia
minimal valine, isoleucine, methionine, and threonine
what enzyme is deficient in methylmalonic acidemia
methylmalonyl CoA mutase/isomerase
what are the 4 main symptoms of methylmalonic or propionyl acidemia
metabolic acidosis
hypoglycemia
ketones
hyperammonemia
what is the urine finding for propionic acidemia
no methylmalonic acid
increased propionic acid
what is the urine lab finding for methylmalonic acidemia
increased methylmalonic acid
increased propionic acid
if vit B12 is deficient molecule in the urine is the most indication will be present in the urine
methylmalonyl CoA
if biotin is deficient, what molecule will be present in urine
propionyl CoA
patients with what clinical features are highly suggestive of vit B12 deficiency
amenia with associated neurological deficits (disruption of myelin synthesis)
if folate is deficient, what molecule will be present in the urine
homocysteine
vit B12 deficiency results in the greatest deficit to what cells
rapidly dividing such as RBC
THF is needed for folate synthesis for DNA synthesis
albinism is caused by a deficiency in what amino acid
tyrosine
albinism occurs due to a deficiency in what production
melanin
what are the 2 main symptoms of albinism
visual defects and photophobia
skin cancer
what is ceramide produced from
serine and palmitoyl-CoA
the production of serotonin and dopamine from tryptophan occurs through what type of reaction
decarboxylation
what are 5 molecules produced from tyrosine
dopamine, epinephrine, norepinephrine, melanin, thyroid hormone
what 2 molecules produce heme
glycine
succinyl CoA
what 3 molecules form creatine
glycine
arginine
SAM (methyl group donor)
how does creatine (muscle protein) become creatine phosphate, which eventually becomes creatinine which is secreted in the urine
creatine kinase phosphorylates creatine
creatine phosphate spontaneously forms creatine
in creatine/creatinine, what molecule provides a reservoir of high energy phosphate
creatine phosphate
the rate of what molecule formation and secretion can be used to measure glomerular filtration rate
creatine
in diabetes induced nephropathy, is the ability to excrete creatine low or high
low
GABA is formed by what type of reaction
decarboxylation with vit B6
GABA is formed by decarboxylation of what amino acid
glutamate
histamine is formed by ___ of histidine (what type of reaction)
decarboxylation
histamine causes vaso___ and broncho___
vasodilation
bronchoconstriction
is glutamate excitatory or inhibitory
excitatory
what is the glutamine activated calcium receptor of excitatory synapses
NMDA
is GABA excitatory or inhibitory
inhibitory
GABA is produced by __ through ___
glutamate
decarboxylation
is glycine an inhibitory or excitatory neurotransmitter
inhibitory
what are the 3 catecholamines
dopamine
norepinephrine
epinephrine
serotonin is formed by what amino acid
tryptophan
catecholamines are formed by what amino acid
phenylalanine
tyrosine
DOPA is the precursor to what molecule
dopamine
dopamine is the precursor to what neurotransmitter
norepinephrine
norepinephrine is the precursor to what neurotransmitter
epinephrine
in production of catecholamines, what enzyme and step requires Vit B6
dopa decarboxylase
dopa–>dopamine
in production of catecholamines, what enzyme and step requires vitamin C
dopamine beta hydroxylase
dopamine–>norepinephrine
in production of catecholamines, what enzyme and step requires SAM
phenylethanolamine N-methyltransferase
norepinephrine–>epinephrine
what type of reactions involve tetrahydrobiopterin
hydroxylation
what type of reaction in neurotransmitter synthesis involves B6
decarboxylation
in Parkinsons, dopamine level is __
in Huntinntons, dopamine level is __
(increased or decreased)
Parkinsons- decreased
Huntingtons- increased
what is the pharmacological treatment for Parkinsons
L-Dopa with a peripheral decarboxylase inhibitor (ex: Carbidopa)
there are 2 categories of dopa receptors, D1 like and D2 like. D1 like include D_, while D2 like include D_
D1= D1, D5
D2= D2, D3, D4
how do D1 like dopamine receptors differ from D2 like in terms of their signaling activity
D1= Gs coupled (increases cAMP)
D2= Gi/G0 coupled (decreases cAMP)
what 3 conditions have to do with dopmine
parkinsons
huntingtons
schizophrenia
the hydroxylation reaction of dopamine to norepinephrine involves use of what 2 cofactors
copper and vitamin C
in the methylation step of neurotransmitter synthesis to produce epinephrine from norepinephrine uses what as a cofactor
SAM
what enzyme converts norepinephrine to epinephrine
phenylethanolamine-N-methyltransferase (PNMT)
what is the main symptoms of pheochromocytomas
hypertension
at what step in the neurotransmitter pathway from phenylalanine to epinephrine do neurons end at
norepinephrine
at what step in the neurotransmitter pathway from phenylalanine to epinephrine does the adrenal medulla end at
epinephrine (whole path)
what are the steps involved in converting tyrosine to melanin in melanocytes
tyrosine–>dope by tyrosine hydroxylase+Cu2+
Dopa–>melanin
what is the impact of cortisol on epinephrine production
cortisol increases gene expression of PNMT, lowing for greater conversion of norepinephrine to epinephrine
how is cortisol able to interact in the medulla with PNMT
cortisol from venous drainage goes through adrenal medulla
catecholamines are what type of receptor type
adrenergic
epinephrine acts mainly through what type of signal transduction
PKA (adenyl cyclase)
catecholamines are inactivated by what 2 enzymes
monoamine oxidase (MAO)
catecholamine O-methyltransferase (COMT)
what does monoamine oxidase produce
NH4+
what is the effect of catecholamine O-methyltransferase
methylate norepinephrine and epinephrine
what is the end product of epinephrine and norepinephrine inactivation
vanillylmandelic acid (VMA)
what condition can be determined by high VMA in urine
pheochromocytoma (high epinephrine and norepinephrine)
what is the end product of dopamine inactivation
homovanillic acid (HVA)
what does high level of HVA indicate
huntingtons (high dopamine)
in the formation of serotonin, tryptophan is first __, then there is a ___
(what type of reaction)
hydroxylation
decarboxylation
what is the parent molecule that forms melatonin in the pineal gland
seratonin
melatonin comes from the amino acid ___
melanin comes from the amino acid __
melatonin= tryptophan
melanin= tyrosine
melatonin is found in the __
melanin is found in __
melatonin= pineal gland
melanin= melanocytes
what is the final product of serotonin inactivation
5-hydroxindole acetic acid (5-HIAA)
serotonin mainly uses what type of receptors
GPCR
the exception of serotonin not using a GPCR is with the receptor __ which is __
5-HT3
ligand gates
what are the 3 clinical correlations with serotonin
depression
migraines
chemotherapy induced emesis
nitric oxide is made from what amino acid
arginine
what is the effect of using nitroglycerine tablets with patients with angine
it produced NO which acts as a vasodilator through the cGMP guanyl cyclase pathway
in purine production, what amino acids contribute N
glutamine, glycine, aspartate
in purine production what amino acid contributes C
glycine
in pyrimidine production what amino acid contributes C
aspartate
in pyrimidine production what amino acids contribute N
glutamine
aspartate
can kidney stones form from purine or pyrimidine degradation
purine
