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137 Cards in this Set
- Front
- Back
in a fed state what are the excess amino acids turned into?
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glucose and acetyl Coa eventually leading to glycogen and triglycerides
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in a fasting state, what is the fate of the carbon core of the amino acid?
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CO2, pyruvate, TCA cycle intermediates, acteyl CoA, acetoacetate ( all to be used for energy)
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what are the four pathways in which the amino acid can generate energy?
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direct oxidation (producing NADH and FADH2 independent of the TCA cycle, oxidation through the TCA cycle, generation of glucose (then oxidizing it in the TCA cycle), and generation of ketone bodies (then oxidizing them in the TCA cycle).
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valine, isoleucine and leucine are good sources for this type of amino acid degradation pathway.
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direct oxidation
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what two organs use the direct oxidation pathway significantly?
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gut(fasting state) and muscle
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what pathway considers glutamine to be a good source of this energy?
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oxidation through the TCA cycle
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what three categories of organs/ cells use the oxidation through the TCA cycle most significantly?
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gut, immune cells, and kidneys
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what are two organs that produce glucose?
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liver and kidney cortex
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what are the 13 purely glucogenic amino acids?
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alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, methionine, proline, serine, valine
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what are the five glucogenic and ketogenic amino acids?
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isoleucine, phenylalanine, threonine, tryptophan, and tyrosine.
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what are the two solely ketogenic amino acids?
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leucine and lysine
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what are the six amino acids that produce energy through direct oxidation when dealing with only glucogenic amino acids?
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valine, threonine, isoleucine, methionine, proline and glycine
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what are the four amino acids that produce energy through direct oxidation when dealing with only ketogenic amino acids?
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threonine, lysine, isoleucine, and leucine
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which non-essential amino acid is essential for children?
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arginine
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where does the sulphur of cysteine come from?
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methionine
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what amino acid produces tyrosine? is the enzyme that produces tyrosine essential or non-essential?
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phenylalanine; essential
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what are the nine essential amino acids?
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histidine, methionine, valine, isoleucine, phenylalanine, threonine, tryptophan, leucine and lysine
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how many of the essential amino acids are glucogenic? ketogenic? both?
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3 glucogenic, 2 ketogenic, 4 both.
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into what category do the bulk of non-essential amino acids fit into: glucogenic, ketogenic, or both?
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glucogenic
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what are the four non-essential amino acids that are synthesized from glycolysis intermediates?
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serine, glycine, cysteine, and alanine
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what are the 2 non-essential amino acids synthesized from oxaloacetate?
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asparagine and aspartate
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what degradation pathway is tyrosine a part of?
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phenylalanine degradation pathway
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what are the four non-essential amino acids synthesized from alpha ketogluterate?
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glutamate, glutamine, proline and arginine
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what is the coenzyme for transamination and deamination of amino acids?
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pyridoxal-phosphate
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what is the coenzyme for metabolism of serine, glycine, and histidine for amino acids?
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tetrahydrofolate
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what is the coenzyme for methionine metabolism in amino acids?
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B12 vitamin
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what is the coenzyme for hydroxylation of phenylalanine, tyrosine and tryptophan in amino acids?
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tetrahydrobiopterin
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what is tetrahydrobiopterin synthesized from?
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GTP
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what is the coenzyme for the oxidative dearboxylation of branched-chain amino acids?
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thiamine-pyrophosphate and lipoate
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what is the major gluconeogenic amino acid?
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alanine
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via what intermediate of glycolysis is serine produced? what intermediate can serine produce?
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3-phosphoglycerate; 2 phosphoglycerate
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what produces glycine and cysteine?
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serine
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if cysteine lost its sulfhydryl group, what would it become?
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pyruvate
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T/F
The conversion from alanine to pyruvate is unilateral. |
FALSE,
it is bilateral via ALT. |
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how is the synthesis of serine regulated?
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via negative feedback on 3 -phosphoglycerate dehydrogenase and phosphoserine phosphatase
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what are the four important metabolites that are produced via serine?
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glycine (neurorasmitter), D-serine (neurotransmitter), phosphatidylserine, sphingosine, and sphingolipids
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in relation to purine synthesis, serine is the ______ one-carbon donor to _____ in humans
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primary; FH4
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what are the symptoms of L-serine deficiency?
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low serine and glycine levels in blood and CSF, microcephaly (infantile form), psychomotor retardation (infantile), seizures, developmental delay (juvenile), behavioral abnormalities (juvenile)
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what are the treatments for L-serine deficiency?
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oral L-serine and glycine
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what are the important metabolites via the production of glycine?
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purines (nucleic acid synthesis), porphyrins (heme), creatine, and glutathione (antioxidant)
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what does threonine release to form glycine?
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acetyl CoA
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glycine can produce what step in the TCA cycle?
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alpha-ketoglutarate
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what type of neurotransmitter is glycine?
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inhibitory
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what are the 2 diseases of glycine degradation? what two directions of the pathway are hindered?
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nonketotic hyperglycinemia (glycine to carbon dioxide) and primary hyperoxaluria type 1 (PLP = pyruvate to alanine and back)
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T/F
other glycine degradation pathways can compensate for the nonketotic hyperglycinemia |
FALSE.
No other can compensate. |
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what are the symptoms of nonketotic hyperglycinemia?
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elevated glycine levels in blood and CSF as well as neurological problems like mental retardation or developmental delay, hypotonia, and seizures.
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what is the treatment for nonketotic hyperglycinemia?
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sodium benzoate (converts glycine to hippuric acid for urinary secretion)
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what is the symptom of primary hyperoxaluria type 1?
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calcium oxalate kidney stones
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what is the treatment for primary hyperoxaluria type 1?
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high fluid intake, vitamin B6 (if responsive), drugs that decrease urinary Ca excretion, and avoid oxalate rich food.
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what are the important metabolites produced via oxaloacetate?
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purines, pyrimidines, and argininosccinate (urea cycle)
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what kind of drug is asparaginase used as?
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an antileukemic drug
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what amino acid is required for growth of fast dividing leukemic cells?
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asparagine
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how does oxaloacetate become asparagine?
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by transaminating to aspartate and then aspartate being converted to asparagine by asparagine synthetase, energy and glutamine
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the important metabolites via the production of glutamine are almost the same as which other compound? what is the only difference?
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oxaloacetate; gluatmine metabolities also include amino sugars. (GAGs)
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what are the important metabolites of glutamate?
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GABA (neurotransmitter), glutathione (antioxidant) and ornithine
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what are the five important metabolites of arginine?
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urea, ornithine, citrulline, nitric oxide, and creatine
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what is the important metabolite of histidine?
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histamine (inflammatory mediator)
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what are the 5 amino acids related to alpha-ketoglutarate?
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glutamate, glutamine, histidine, proline and arginine.
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what is histidinemia? what is the symptom?
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a deficiency in histidase. The symptom will be elevated levels of histidine in blood and urine
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what is used to monitor folic acid deficiency in relation to histidine metabolism?
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N-forminminoglutamate (FIGIu)
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what is FIGIu a precursor for?
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glutamate
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how is the metabolism of cysteine regulated?
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negative feedback on cystathionine synthase
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what are the 2 important metabolites produced via cysteine metabolism?
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glutathione and Coenzyme A
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what is the universal sulfate donor?
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PAPS
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what are the four amino acids related to succinyl CoA?
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methionine, threonine, isleucine, and valine
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what is the main pathway of threonine degradation?
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threonine to alpha-ketobutyrate losing an NH3 in the process
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what are the important metabolites of SAM?
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phosphatidylcholine, creatine, carnitine, melatonin, and epinephrine
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what are the 2 disorders of methionine/cysteine metabolism?
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hereditary homocystinuria and hereditary cystathioninuria
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what part of the pathway cannot function normal in hereditary homosystinuria? hereditary cystathionuria?
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homo: cystathione synthase and cysta: cystathionase
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which enzyme is affected in the methionine/cysteine metabolism disorders?
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PLP
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defiency in what vitamin and what enzyme can lead to the methionine/cysteine metabolism disorders?
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PLP and 12
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which disorder has a low blood levels of B12? (methionine, homocysteine, or cystathionine)
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methionine
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which disorder has a low blood level of cystathione synthase? (methionine, homocysteine, or cystathionine)
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cystathionine
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which disorder has elevated blood levels of cystathionase, cystathione synthase and B12? (methionine, homocysteine or cystathionine)
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homocysteine
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what are the symptoms of cystathioninuria?
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elevated cystathionine levels in blood and sometimes mental retardation
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what are the treatments for cystathioninuria?
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dietary restriction of met, and supplementation of cys, vitamin B6 (PLP) supplementation (if responsive)
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what are the symptoms for homocystinuria?
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elevated homocystine levels in blood and urine, mental retardation or developmental delay, ectopia lentis, skeletal abnormalities (marfan-like), and increased clot formation
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what are the treatments for homocystinuria?
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dietary restriction of Met, and supplementation of cys, vitamin B6 (PLP), B12, and folic acid supplementation (if responsive) and betaine supplementation (methylation of homocysteine).
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in what country is homocystinuria most present? (norway, germany or ireland)
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norway
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what percentage of Propionyl CoA is produced from amino acids in the human body?
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~50%
side note: ~30% from odd-chain length FA and ~20% derive from intestinal bacteria |
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what 2 things can cause propionic acidemia?
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biotin deficiency and propionyl-CoA carboxylase deficiency
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what 2 things can cause methylmalonic acidemia?
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B12 deficiency and methylmalonyl-CoA mutase deficiency
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what are the symptoms of propionic and methylmalonic acidemia?
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ketoacidosis (increased levels in blood and urine) and secondary hyperammonemia (encephalopathy, lethargy, vomiting, hypotonia)
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propionyl and methylmalonyl-CoA are competitive inhibitors of what enzyme?
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N-acetylglutamate synthetase
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what are the five treatments for propionic and methylmalonic acidemia?
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intravenous bicarb (balance blood pH), oral neomycin treatment (to reduce propionate production via gut's flora), L-carnitine treatment (to form propionylcarnitine and release CoA), Biotin or B12 supplementation (if responsive), and low protein, high carb diet restricted in the involved amino acids.
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how many of the amino acids involved in propionic/ methylmalonic acidemia are essential?
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all of them! 4.
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what are the cofactors of alpha-keto acid dehydrogenase?
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thiamine-pyrophosphate, lipoate, and FAD
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which of the branched-chain amino acids produces the most energy from direct oxidation?
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valine 9 ATP
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how many branched-chain amino acids are there? what are they?
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3: valine, isoleucine, and leucine
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what type of amino acids are defective in maple syrup urine disease?
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branched-chain
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what enzyme is defective in maple syrup urine disease?
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alpha keto acid dehydrogenase
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what are the symptoms of maple syrup urine disease?
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elevated branched-chain amino acids (esp leucine) in blood and branched-chain ketoacids in blood and especially urine. encephalopathy (lethargy, poor feeding, apnea, opisthotonus, coma)
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how is maple syrup urine disease managed?
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branched-chain amino acid restricted high calorie diet. BCAA free formulas supplemented with limited amounts of valine and isoleucine.
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which amino acid is the most restricted in the management of maple syrup urine disease?
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leucine
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what are the first signs of maple syrup urine disease?
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maple syrup odor of urine (5-7 days after birth) and of earwax (12-24 hr after birth)
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which amino acids are transported through the blood-brain barrier by the same transporter?
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BCAAs, phe, tyr, trp, his and met
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what four amino acids are important precursors for neurotransmitters/ hormones in the brain?
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tyr, trp, his and met
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what what type of cell is the amino group of BCAAs used for glutamate synthesis?
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astroglial cells
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where is glutamate converted to glutamine? where is it converted back to glutamate?
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astroglial cells; neurons
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what other neurotransmitter does glutamine produce?
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GABA
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what are the neurological problem of Maple syrup urine disease II?
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leucine intoxication
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what happens during leucine intoxication?
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leucine overloads the blood-brain barrier transporter blocking the transport of Phe, Tyr, Trp, His and Met. This leads to a reduced production of neurotransmitters/hormones. alphaKIC reverses the transamination reaction (which was BCAAs to BCKA and alpha-ketoglutarate to glutamate) and decreases glutamate and gltamine levels in astroglial cells. Low glutamate concentration = stops ammonia removal by glutamine synthase. Reduced glutamine levels cause decreased glutamate and GABA production.
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what are the main culprits of leucine intoxication?
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leucine and its ketoacid- alpha ketoiscaproic acid
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what is the only non-essential ketogenic amino acid?
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tyrosine
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what are the three catecholamines who have L-Dopa as their precursor?
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dopamine, norepinephrine, and epinephrine
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how is tyrosine converted to dopaquinone? L-dopa?
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via tyrosinase; via tyrosine hydroxylase
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what is dopaquinone the precursor for?
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melanin
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what are the 3 disorders of phenylalanine/tyrosine metabolism I? what is the enzyme that is deficient in each disorder?
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hyperphenylalaninemias (phenylalanine hydroxylase), tyrosinemia II (tyrosine aminotransferase) and oculocutaneous albinism type 1 (tyrosinase)
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what is an important cofactor in Phe hydroxylation?
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tetrahydrobiopterin
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what is another cause of hyperphenylalaninemia besides a deficiency in phenylalanine hydroxylase?
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tetrahydrobiopterin deficiency
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which cause of hyperphenylalaninemia tends to be more severe? why?
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tetrahydrobiopterin deficiency caused hyperphenylalaninemia because of the inability to synthesize important neurotransmitters/hormones
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what are the symptoms of hyperphenylalaninemias (phenylketonuria)?
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elevated phenylalanine levels in blood, phenyl ketones and other phenylalanine metabolites in urine (musty odor), neurological problems (microcephaly, mental retardation, tremors, seizures), decreased serotonin and catecholamine levels in brain and decreased myelin formation around neurons. Can also cause decreased hair and skin pigmentation
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what are the treatments for PKU?
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Phe restricted protein diet and Phe-free medial formulas. Avoid aspartame (artificial sweetener), and BH4 (tetrahydrobiopterin) supplementation if pt responds.
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what are the symptoms of tyrosinemia II?
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elevated tyrosine levels in blood, elevated tyrosine metabolites in urine, painful corneal and skin lesions (tyrosine crystals), neurological problems (developmental delay)
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what are the symptoms of oculocutaneous albinism type 1?
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greatly reduced or complete lack of melanin production, white skin, white hair, skin sensitivity to sunlight, and translucent iris.
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what are the treatments for oculocutaneous albinism type 1?
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skin and eye care
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what are the 2 disorders of phenylalanine/tyrosine metabolism II? what enzymes are deficient?
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alkaptonuria (homogentisate oxidase) and tyrosinemia (fumarylacetoacetate hydrolase)
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what step in the pathway from phenylalanine to fumarylacetoacetate is inhibited by a drug called nitisinone?
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the degradation of hydroxyphenylpyruvate and subsequent formation of fumarylacetoacetate
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what are the symptoms of Tyrosinemia I?
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hepatic failure, kidney failure, rickets, elevated plasma phenylalnine, tyrosine, methionine , and sigma aminolevulinic levels. They will also have elevated tyrosine metabolites in urine.
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how can tyrosinemia I cause hepatic failure, kidney failure and rickets?
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hepatic: toxic levels of fumarylacetoacetate in hepatocytes. Kidney: high levels of succinylacetone in blood and urine. Rickets: high excretion of phosphate in urine (low bone density)
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what do elevated plpasma sigma aminolevulinic acid levels inhibit? what does it cause?
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heme synthesis; change in mental status, abdominal pain, and respiratory failure.
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what are the treatments for tyrosinemia I?
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Nitisinone, Phe and Tyr restricted protein diet, dietary calcium and vitamin D supplementation (against rickets), and liver transplantation
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what are the symptoms of alkaptonuria?
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elevated homogentisic acid levels in urine (turns black when left standing), ochronosis (bluish-black pigmentation of connective tissues), arthritis and often associated with kidney stones
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why is ochronosis caused by alkaptonuria? what is the first sign?
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accumulation of homogentistic acid in issues; first sign is the brown pigmentation of the eyes.
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what are the treatments for alkaptonuria?
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joint pain management or surgery.
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what is serotonin responsible for?
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gut movement and appetite
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what is melatonin responsible for?
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sleep-wake cycle (pineal gland)
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what are the 2 general reasons behind what causes the diseases of amino acid metabolism?
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mutated enzymes (autosomal recessive) or insufficient co-factors
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when will a human under normal physiological conditions have a positive nitrogen balance?
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during growth (from infancy to adolescence, pregnancy and lactation) and during recovery from illness or malnutrition
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when will a human under normal physiological conditions have a negative nitrogen balance?
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during illness and malnutrition
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what are food sources that contain all 9 essential amino acids?
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mostly animal products: egg, milk, cheese, meat, poultry, fish. Plant source: soy products
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what are the food sources that lack some of the essential amino acids?
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mostly plant products: vegetables, grains, legumes, nuts, and seeds. as well as gelatin.
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what 3 amino acids does gelatin lack?
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Trp, Val and Ile
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what are symptoms of pellagra?
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dermatitis, diarrhea, dementia and death
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what causes kwashiorkor? what age group does it affect?
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breast-fed entirely then rapidly weaned. switched from breast milk to diet with little protein. age: 1.5-2 YO
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what is marasmus?
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chronic general energy malnutrition- starvation
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what are the symptoms of marasmus?
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emaciated appearance, no body fat- bones, ribs, vertebral column are clearly seen.
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