TBL Prep Flashcards
What are the essential amino acids?
HILL My PT TV Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine
What is the weird reason that we need amino acids?
substrate for heme, purine, pyrimidine, melanin
What are the 5 important cofactors in amino acid metabolism?
- THF
- SAM
- Biotin
- THB
- Pyridoxal Phosphate (PLP)
Where is THF from? What does it do?
synthesized by bacteria
transfers single carbons
How is SAM synthesized?
Synthesized from ATP & Methionine
What does SAM do?
transfers methyl groups
What does biotin do?
transfers CO2
What is THB involved in?
tyrosine synthesis
involved in oxidation reaction
Remember: “think outside the BOX”
What does PLP do? What types of reactions is it involved in? What is it a coenzyme for?
holds nitrogen–>how cute
involved in transaminase reaction
coenzyme for vitamin B6
Once again, what are the energy results of the TCA cycle?
3 NADH=9 ATP
1 GTP=1 ATP
1 FADH2=2 ATP
Which enzyme of TCA is bound to the inner mitochondrial membrane?
succinate dehydrogenase
What part of the TCA cycle does excess EtOH feed in to? How?
Acetyl CoA!
EtOH–>Acetaldehyde–>acetic acid–>acetyl CoA
What are the 2 effects of excess citrate? Where does it go?
Gets out of the mitochondria and inhibits glycolysis & goes into Fatty Acid Synthesis.
What is the reaction for the synthesis of glutamate?
alpha-KG + NH4+ + NADPH–>Glutamate +NADP+ + H2O
Enzyme: glutamate dehydrogenase
When does the synthesis of glutamate occur? When does it occur?
when there are toxic amount of ammonia, mainly in the liver…
What is the reaction for the formation of glutamine?
Glutamate + ATP + NH3–>Glutamine
Enzyme: glutamine synthetase
What is the reaction for the formation of glutamate from glutamine?
Glutamine –> Glutamate + NH4+
Enzyme: glutaminase
How is non-toxic version of ammonium transferred around?
thru glutamine
What is the most abundant circulating AA?
glutamine!
Glutamine is _____ donor in many ____ reactions.
nitrogen donor
many synthesis reactions
Which of the following can move across a cell membrane:
glutamine
glutamate?
glutamine!!
What is the reaction for making alanine?
Pyruvate + AA –>Alanine + alpha keto acid
Enzyme: ALT: alanine transaminase
T/F Transaminases are used in irreversible reactions.
FALSE
they are reversible reactions, highly reversible
What cofactor do all transaminases require?
PLP found in Vitamin B6
Which enzyme’s levels are checked if you suspect liver damage?
ALT
What is the reaction for the formation of aspartate?
OAA + Glutamate–>Aspartate + alpha KG
Enzyme: GOT: glutamate-OAA transaminase
What is the reaction for the formation of asparagine?
Aspartate + ATP + Glutamine–>Asparagine + Glutamate
Enzyme: Asparagine Synthetase
Is there a reverse reaction for asparagine? If so, what is it?
YES, glad you asked.
Asparagine –> Aspartate + NH4+
Enzyme: asparaginase
Leukemia patients are sometimes unable to synthesize _____. Thus, _____ is sometimes used as a treatment.
asparagine
asparaginase is used as a treatment
Asparagine is often ________.
glycosylated
What is an enzyme that humans don’t express involved in AA synthesis?
asparaginase
What is the reaction for the formation of serine?
3PG + Glutamate –> Serine + alpha KG + NADH
What is the reaction for the formation of glycine?
Serine + THF–> Glycine
What is the reaction for the formation of methionine?
Homocysteine + methyl-THF –> Methionine + THF
uses Vit B12
How do you make homocysteine?
via Met + ATP–>SAM–>SAHcys–>Homocysteine
What is the intermediate b/w homocysteine & Cysteine?
cystathionine
Which AA must be added in to make cystathionine?
Serine!
How do you make cystathionine?
Homocysteine + Serine –> Cystathionine
Enzyme: Cystathionine Synthase
Requires: PLP
How do you make cysteine from cystathionine?
Cystathionine –> Cysteine
Enzyme: cystathionase
Requires: PLP
What causes homocystinuria? What are the effects of this condition? What are its treatments?
deficiencies in cystathionine synthase or cystathionase mental deficiency vascular thrombosis thinning & lengthening of long bones osteoporosis Treatments: dietary, vitamin
What is the reaction for the formation of tyrosine?
Phenylalanine + THB–>Tyrosine + DHB
Enzyme: Phenylalanine hydroxylase
What does tyrosine go on to form? Which enzyme is required for this to happen?
goes on to form melanin
Enzyme: tyrosinase
Once THB–>DHB how do you renew it again?
DHB–>THB
Requires: NADH
Enzyme: DHB reductase
What happens when you have too much phenylalanine?
You get formation of phenylketones
Then you can get PKU
What are the symptoms of PKU? What are the treatments?
Symptoms: mental retardation, light skin color
Treatments: dietary, no aspartame
What is proline made from? What feed in does it require?
made from glutamate
requires NADH
What types of ubiquination make for urgent degradation?
longer chains
What type of ubiquination makes for fast degradation?
when the N-terminus has destabilizing things
LADS are FAST
leucine
arginine
What type of ubiquination makes for slow degradation?
when the N-terminus has stabilizing things
PMS makes you SLOW
proline
methionine
What causes Alzheimer’s & Parkinson’s?
formation of protein structures in neurons
What causes cystic fibrosis?
rapid degradation of chloride channels
What causes Liddle’s Syndrome? What is the significance of this?
the sodium channel that is inserted into the nephron isn’t degraded…
this leads to excess sodium absorption
this causes early-onset HTN
What 2 things cause negative nitrogen balance?
stress hormones
cytokines
Which 3 types of people will have a positive nitrogen balance?
children
pregnant women
body builders
What is nitrogen balance?
Nitrogen balance is when Nitrogen Intake = Nitrogen loss
What defect leads to oxaluria type I?
a deficiency of glycine transaminase
Can’t take glyoxylate–>glycine
What defect leads to nonketotic hyperglycinemia?
A lack of glycine cleavage enzyme
Can’t break down glycine!
What defect leads to homocystinuria?
A lack of cystathionine synthase
Can’t make cysteine
get a buildup of homocysteine
What enzyme deficiency leads to PKU?
phenylalanine hydroxylase
What causes tyrosinemia type II?
a defect in tyrosine aminotransferase
What causes tyrosinemia Type I?
a defect in fumarylacetoacetate hydroxylase
get a buildup of an intermediate instead of fumarate!
WHat cause alkaptonuria?
deficiency in homogentisate oxidase
get a buildup of an intermediate instead of fumarate
What causes histidinemia?
a deficiency of histidase
What intermediate accumulates w/ a folate deficiency?
FIGLU
formimino glutamic acid
What defect leads to methylmalonic aciduria?
a defect in methylmalonyl CoA mutase
can’t make succinyl CoA
What causes maple syrup urine disease?
a deficiency of branched chain alpha keto acid dehydrogenase complex
How do you degrade branched AA?
transamination & then oxidative decarboxylation
What are some examples of breakdown products of branched AA catabolism?
propionyl CoA
Acetyl CoA
Acetoacetate
Which AA are catabolized in the intestinal mucosal cells?
glutamate
glutamine
Where are most AA metabolized?
in the liver
How are branched chain AA metabolized?
they leave the liver & go to muscle for the transamination reaction; then they return to the liver for oxidative decarboxylation
What is the major source of AA during fasting?
muscle protein!
2 AA go to glucose thru gluconeogenesis during fasting…which AA? Where do they go to do this?
glutamine–>kidneys & intesines
alanine–>liver
In the degradation of phenylalanine…what bad things can happen? What accumulates in each case?
deficiency of phenylalanine hydroxylase
deficiency of DHB reductase
**In both cases: phenylalanine accumulates
What condition does a deficiency of phenylalanine hydroxylase cause? What are the symptoms?
PKU (classical)
Mental Retardation
What condition does a deficiency of DHB reductase cause?
PKU (non-classical)
Mental Retardation
In the degradation pathway of tyrosine…what can go wrong? What accumulates in each case?
a deficiency of homogentisate oxidase (homogentisate acid)
a deficiency of fumarylacetoacetate hydroxylase (fumarylacetoacetate)
a deficiency of tyrosine aminotransferase (tyrosine)
What condition does a deficiency of homogentisate oxidase & an accumulation of homogentisate acid cause? What are the symptoms?
Alcaptonuria
black urine
arthritis
What condition does a deficiency of fumarylacetoacetate hydroxylase & an accumulation of fumarylacetoacetate cause? What are the symptoms?
Tyrosinemia I
Liver Failure
Early Death
What condition does a deficiency of tyrosine aminotransferase and an accumulation of tyrosine cause? What are its symptoms?
Tyrosinemia II
neurological defects
In the degradation of methionine…what can go wrong? What accumulates?
a deficiency of cystathionase (cystathionine)
a deficiency of cystathionine synthase (homocysteine)
What condition does a deficiency of cystathionase & an accumulation of cystathionine cause? What are its symptoms?
Cystathionuria
Benign
What condition does a deficiency of cystathionine synthase & an accumulation of homocysteine cause? What are its symptoms?
homocysteinuria
cardiovascular & neurologic problems
In the degradation of glycine…what can go wrong? What accumulates?
a deficiency of glycine transaminase (glyoxylate)
a deficiency of glycine cleavage enzyme (glycine)
With a deficiency of glycine transaminase & an accumulation of glyoxylate…what condition results? What are its symptoms?
Primary Oxaluria Type I
Renal failure w/ stone formation
What condition is caused by a deficiency of glycine cleavage enzyme & an accumulation of glycine? What are its symptoms?
Hyper Glycinemia
Mental Retardation
In the degradation of branched AA what can go wrong & what accumulates?
a deficiency of branched chain alpha keto acid dehydrogenase (alpha keto acids)
What condition is caused by an accumulation of alpha keto acids? What are its symptoms?
Maple Syrup Urine Disease
Mental Retardation
What are the 3 branched chain AA?
LIV:
Leucine, Isoleucine, Valine
What is the purpose of the urea cycle?
to get rid of NH4+, which is a neurotoxin.
What happens to urea in the case of renal failure?
the BUN (urea in the blood) rises sharply: called uremia
How can urea cause kidney stones?
a bacteria enzyme in the urine can cleave urea…this has 2 effects: alkalinizing the urine & precipitating out magnesium ammonium phosphate
If you have an inherited deficiency of some of the urea cycle enzymes…what happens?
Hyperammonemia & Encephalopathy
lethargy, vomiting, irritability
During failure of the urea cycle…why do you have ATP deficiencies?
alpha KG is converted into glutamine
What is the therapy for urea cycle enzyme deficiencies?
limit protein intake
remove excess ammonia
replace urea cycle intermediates
maybe liver transplant
What is the first step in the urea cycle? Where does it occur?
Liver, mitochondrial matrix
NH4+ + 2ATP + CO2–>Carbamoyl Phosphate
Enzyme: carbamoyl phosphate synthetase I
What does a buildup of carbamoyl phosphate do?
leads to orotate in your urine
Once you have carbamoyl phosphate in the mitochondrial matrix of the liver…what is the next step?
Ornithine combines w/ carbamoyl phosphate in the mitochondrial matrix to make citrulline.
Enzyme: ornitine transcarbamylase
What do you do with your citrulline?
Citrulline + ATP + Aspartate–>Arginosuccinate
Enzyme: Arginosuccinate Synthetase
Where did you get the aspartate for the last step?
From the TCA cycle? It was shoved into the cystol from the mitochondrial matrix…
After you have arginosuccinate…what is the next step?
Arginosuccinate–>Arginine + Fumarate
Enzyme: Arginosuccinate Lyase
What happens to the fumarate you just threw off?
It is converted into malate & shunted back into the mitochondrial matrix to become a part of the TCA cycle.
Now that you have arginine…what happens?
Arginine–>Ornithine & kicks off a urea
Enzyme: arginase
**note the ornithine will go & combine w/ the carbamoyl phosphate…
HOw many ATP does one urea cycle require?
4 ATP
