Amino Acid Metabolism

rastarr80's version from 2015-11-18 04:07

Section 1

Question Answer
What is positive nitrogen balance?More nitrogen is consumed than excreted, implies net protein synthesis.
When does one have positive nitrogen balance?during recovery from starvation, growth, and pregnancy
What is negative nitrogen balance?More nitrogen is excreted than consumed, implies mobilization of amino acids, tissue necrosis, or poor diet
When does one have negative nitrogen balance?during starvation, burns, surgery, infection and inflammation
What are the essential amino acids?The 10 essential amino acids are: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine and Arginine (required for Children)
How is alanine synthesized?from pyruvate via alanine transaminase
How is glutamine synthesized from glutamic acid?By glutamine synthetase which requires ATP and ammonia
How is glutamic acid synthesized from alpha-ketoglutarate?By glutamate dehydrogenase which required NADPH
What is the intermediate in the conversion of methionine to cysteine?S-adenyl methionine (SAM), this also requires serine, methylo-folate, and B12
What amino acid is the precursor for Proline?glutamate
What can be transaminated to produce Aspartate?oxaloacetate
How is aspartate converted to asparagine?asparagine synthetase and ammonia
How is glycine converted to serine?Serine hydroxymethyl and requires Methylene-THF

Section 2

Question Answer
What is the purpose of amino acid catabolism during fasting?for energy production
Which amino acid carries nitrogen from the muscle tissue to the liver?alanine, through the alanine cycle
Skeletal muscle amino acids are mobilized by what?glucocorticoids, they have an anti-insulin affect post receptor
What is Blood Urea Nitrogen a measure of?urea in the blood
How is nitrogen removed from amino acids before their catabolism?by Transaminases, amino acids are turned into alpha-keto acids
What happens to nitrogen after it has been removed from amino acids by transaminases?its converted to ammonia by glutamate dehydrogenase, then released in urine
What happens to alanine once it enters the liver from the muscle?Alanine loses ammonia to urea cycle, is converted to pyruvate and then glucose.
What happens to glucose once it gets back into the muscle in the alanine cycle?It is converted to pyruvate and then reacts with BCAAs to form alanine and BCKA
Where are branched chains burned?In the muscle
What do branched chains produce when they are burned?Branched Chain Keto Acids, which then become alpha keto acids which enter the TCA cycle
What is the net result of the alanine cycle?transport of nitrogen to the liver for the urea cycle

Section 3

Question Answer
The urea cycle happens in what 2 sites?Mitochondria and cytoplasm
What are the 2 mitochondrial reactions of the urea cycle?Carbamoyl phosphate synthesis and citrulline synthesis by ornithine transcarbamolase
What is the rate limiting step of the urea cycle?Carbamoyl phosphate synthetase (CPS)
What is the carbon source for the carbamoyl phosphate synthesis reaction?Glutamate from the Glutamate dehydrogenase action
How is carbamoyl phosphate converted to citrulline in the mitochondria?Ornithine transcarbamolase by combining ornithine and carbamoyl phosphate
Where does citrulline react with aspartate and what is the enzyme?Cytoplasm, Argininosuccinate synthase, which produces argininocuccinate
What is the function of argininosuccinate lyase?Cleaves argininosuccinate into fumarate and arginine
What enzyme splits arginine into urea and ornithine?arginase
How does N-acetylglutamate affect the urea cycle?it is a positive allosteric affector of Carbamoyl phosphate synthetase (CPS)
What produces N-acetylglutamate?high protein meals produce large amounts of ammonia producing N-acetylglutamate
What disease results from a deficiency in the urea cycle (more severe with CPS I or ornithine transcarbamoylase) with neurological symptoms?hyperammonemia
What happens in hyperammonemia with secondary oroticaciduria?Ornithine Transcarbomylase deficiency where carbamoyl phosphate gets into cytoplasm and is converted to carbamoyl aspartate that builds up and is converted to oratate which leads to orotic acid excess
How is hyperammonemia treated?with a mix of benzoic acid and phenylacetic acid
How does benzoic acid work in treatment?benzoate and glycine pull nitrogen out as hippuric acid that is secreted in the urine
How does phenylacetic acid work in treatment?Phynlacetate and glutamine pull out nitrogen as phenyacetylglutamine that is secreted in urine
Does urine production increase of decrease during extreme starvation?Increases due to protein degradation
How can one acquire hyperammonemia?alcohol cirrhosis (serum ammonia increased) and Reye's syndrome (fatty liver)

Section 4

Question Answer
What TCA cycle intermediates are entry points for amino acids?Pyruvate, alpha-ketoglutarate, succinyl-CoA, Fumarate, OAA, and Acetyl-CoA
What is the end product of metabolism of a ketogenic amino acid?acetoacetyl-CoA, they can become ketone bodies
How is glutamine synthesized?With glutamine synthase, ATP, and ammonia from Glutamate.
How is glutamine degraded?With Glutaminase, giving off ammonia and glutamate
How is asparagine synthesized?With asparagine synthase, ATP, and ammonia from aspartate
How is asparagine degraded?With asparaginase, giving off ammonia and aspartate
What does the interconversion of serine and glycine provide? a route for glycine to pyruvate
The interconversion of serine and glycine requires what?Serine hydroxymethyl transferase and methylene-THF (folate)
What are BCKAs converted to by multienzyme complexes?to CoA-thioesters
Valine and Isoleucine are converted into what CoA-thioester?succinyl-CoA that enters the TCA cycle
Leucine is converted to what CoA-thioester?acetoacetyl-CoA which is ketogenic
What is the maple syrup urine disease?BCKA dehydrogenase complex deficiency where the alpha-ketoacids give urine a maple syrup odor and there are neurological symptoms with fever and infection
What is methylmalonic aciduria?BCKAs are an additional source of propionyl -CoA which feeds into the methylmalonic pathyway causing overproduction which spills into the urine

Section 5

Question Answer
What amino acids are converted to glutamate so they can enter the TCA cycle?Glutamine, proline, histidine, and arginine
How does glutamate enter the TCA Cycle?It is transaminated into alpha-ketoglutarate
How can the conversion of histidine to glutamate test for folate deficiency?Oral histidine will produce FIGLU in the urine when folate is deficient because histidine is converted to FIGLU then to glutamate by THF
What enzyme deficiency results in histidemia?Histidase, which converts histidine into FIGLU
FIGLU is converted into glutamate by what?THF
How is methionine converted to S-adenosylmethionine (SAM)?With ATP!
What is lost by SAM to become SAH (S-Homocysteine)?methyl group
How is methionine converted to succinyl-CoA?methionine to SAM to SAH and then by the cystathionine pathway - to propionyl-CoA to methomalonyl-CoA to succinyl-CoA using B12
A deficiency of the cystathionine synthase produces what disease?Homocystinuria
How can folate be trapped in the cell?by a polyglutamate tail. Methotrexate (cancer drug) is also polyglutamated, but if it is administered, then folate is able to bypass the polyglutamation and can become active again
What causes a methyl trap?B12 deficiency, methylfolate piles up since there is only one reaction that uses methyl-folate. Overtime, a secondary deficiency will result from folate
What enzyme deficiency results in alkaptonuria?homogentisate oxidase
What is the key characteristic of alkaptonuria?Ink black urine from homogensitase oxidizing. It also can deposit in joints causing joint replacements by age 50 and back pain at age 30
What is homogensitate an intermediate of?Tyrosine conversion to fumarate
How is phenylalanine converted to DOPA?Phenylalanine to tyrosine to DOPA
What is DOPA a precourser for?Catecholamines (like dopamine)
What defect results in PKU I?Defect in phenylalanine hydroxylase, can't convert phenylalanine into tyrosine
What pathways do phenyalanine get shunted into with PKU?phenylpyruvate, phenylacetate, and phenyllactate (all are neurotoxins)
What defect results from PKU II?Defect in Dihydrobiopterin reductase (NADPH required) which regenerates B4 which is needed for phenylalanine hydroxylase conversion of phenylalanine to tyrosine
If PKU isn't picked up, what can happen?Mental retardation which should be grown out of by 6 years old. Due to neurological damage
What is a way to deal with PKU?Low phenylalanine diet
If a low phenylalanine diet doesn't work, what disease might be happening?PKU-II, still have neurological damage

Section 6

Question Answer
What is the amino acid precursor for serotonin and melatonin?Tryptophan
Where is serotonin produced?In the brain, pineal gland, and chromaffin cells in gut
Where is melatonin produced?in pineal gland (made from serotonin)
What is the function of melatonin?makes you go to sleep
What is the function of serotonin?is a neurotransmitter and involved in peripheral vasodilation
How is carnitine produced?Trimehyllysine is celaved from lysine and then it goes through a pathway involving ascorbate and iron which produces carnitine
What happens when you have deficiencies in carnitine production?myopathic or systemic symptoms
What amino acid is used to synthesize niacin?tryptophan
What defect produces cystinuria?Defect in membrane transporter in intestinal lumen that keeps lys, arg, ornithine, cysteine in urine, recessive inheritance
What is the clinical presentation of cystinuria?Abnormal amount of dibasic amino acids in the urine, often caused kidney stones
What is hartnup disease?defective intestinal absorption of tryptophan and niacin, recessive inheritance
What is the clinical presentation of hartnup disease?Pellegra symptoms - dermatitis and neurological
What are the precursors for the synthesis of creatine?arginine, glycine, SAM
What is the function of creatine phosphate?good energy storage, provides initial energy for muscle contraction, not good for sustained use
What is the origin of creatinine?its the nonenzymatic degradation of creatine phosphate and is excreted in the urine
What is the significance of creatinine?It can be used in a urinalysis of glomerular filtration rate (shows the state of the kidney)
How is melanin formed?Pheynalanine to tyrosine to DOPA and then to melanin by copper containing tyrosinase
What is the function of melanin?functions as a UV sponge because the tyrosine absorbs UV light and it gives color to the skin. It absorbs UV radiation before it reaches the DNA
Where is melanin produced?in the melanocytes which are found in the skin, hair, retina and iris. On the "sunny side" of the cell (distal to the nucleus)