Amino Acid Metabolism Flashcards
Basic outline of fuel metabolism:
Amino acid metabolism is diverse and impinges on ____ and the ___ ___.
Glycolysis
TCA cycle
Three key cofactors for enzymes in amino acid metabolism:
_____, ____, and _____.
Pyridoxal phosphate (PLP)
Tetrahydrofolate (FH4)
Tetrahydrobiopterin (BH4)
_____ enzyme performs transaminations, deaminations, carbon chain transfers, derived from B6
PLP
____ enzyme performs one carbon transfers, derived from folate (vitamin B9)
FH4
____ enzyme performs ring hydroxylations such as phenylalanine to tyrosine. It is synthesized from GTP.
BH4
Eleven non-essential amino acids can be made using ____ from glucose and other amino acids
Carbon
Nine other essential amino acids are required in the ___.
Diet
____ is conditionally essential. Children need it in their diet but adults can generally synthesize enough
Arginine
Essential amino acids:
Tyrosine is a nonessential amino acid. It requires dietary ____ for synthesis. In the absence of ____ ____, tyrosine becomes an essential amino acid
Phenylalanine
Phenylalanine hydroxylase
Cysteine is a nonessential amino acid that requires dietary ____ to donate a sulfur.
Methionine
Amino acids can be derived from and degrade into ____ intermediates, ___ ___ intermediates, ___ ___, and ____
Glycolysis
TCA cycle
Acetyl CoA
Acetoacetate
Amino acids derived from glycolytic intermediates:
Serine, glycine, cysteine, and alanine
Serine can be synthesized from the glycolytic intermediate ______, it’s nitrogen comes from the amino acid ____.
3-phosphoglycerate
Glutamate
Serine degradation produces _____.
2-phosphoglycerate
Serines side chain is transferred to _____ to make the simplest amino acid, glycine. Glycine can also be produced by _____ from dietary threonine.
Tetrahydrofolate (FH4)
Beta-elimination
Excess glycine can be converted to _____ through transamination or oxidative deamination. ____ metabolites can be oxidized to carbon dioxide or excreted in the urine.
Glyoxylate
Glyoxylate
Serine and a sulfur from homocysteine are joined to make _____.
Cysteine
Degradation of cysteine forms ____ ___, which acidifies urine. The sulfuric acid is also used to synthesize _____, an activated sulfate for use in other reactions.
Sulfuric acid
PAPS
_____ is the major gluconeogenic amino acid. It is transaminated by alanine aminotransferase (ALT) to ____. ALT is expressed at high levels in the hepatocytes, ALT in the ____ is an indicator of liver damage.
Alanine
Pyruvate
Blood
Amino acids derived from TCA cycle intermediates:
From alpha-ketoglutarate:
From oxaloacetate:
Glutamate, glutamine, arginine, proline
Aspartate, asparagine
Oxaloacetate can be converted into Aspartate through _____ catalyzed by Aspartate aminotransferase (AST). The amino group is donated by ____.
Transamination
Glutamate
Aspartate can accept an amine group from glutamine to make ____.
The enzyme ____ can hydrolyze the amino group, forming ammonium and Aspartate.
Asparagine
Asparaginase
Glutamate can be produced from alpha-ketoglutarate by ___ ____ or through transamination by ____ ____ (AST) or ___ ___ (ALT).
Glutamate dehydrogenase
Aspartate aminotransferase
Alanine aminotransferase
Glutamine synthetase is one of three ____ fixing enzymes. It is important in nitrogen transport. _____ can deaminate glutamine, producing glutamate and free ammonium.
Ammonium
Glutaminase
____ can be synthesized from glutamate and also oxidized back to glutamate.
Proline
____ ____, an intermediate between glutamate and proline, is transaminated to form ornithine, an amino acid of the urea cycle.
Glutamate semialdehyde
Amino acids that can contribute the four carbons of Malate are considered ____. Amino acids that can only form acetyl CoA can not contribute carbon to Malate, because two carbons are lost in the TCA cycle as ___ ___.
Gluconeogenic
Carbon dioxide
Disorders of amino acid metabolism:
Isoleucine, valine, and leucine contribute to ___ ___ ___ disease. Phenylalanine and tyrosine contribute to ___ and ______ and _____.
Maple syrup urine
PKU
Tyrosinemia type I and II
Alcaptonuria
The three branched chain amino acids make up 20 to 30% of dietary ___. High levels are ____ so defects in their metabolism can have severe effects.
Protein
Toxic
Maple syrup urine disease MSUD is caused by inherited loss of function in the ___ ____ of branched chain keto acid ____.
E1 subunits
Dehydrogenase
Alpha-keto acid dehydrogenase is a ___ ___ step in branched chain amino acid degradation. It has a similar organization to pyruvate dehydrogenase.
Rate limiting
____ refers to the reduced form of the amino acid. The sulfhydryl can be oxidized by forming a disulfide bond and forming _____, which is more hydrophobic.
Cysteine
Cystine
Maple syrup urine disease
Presentation:
Labs:
Treatment:
Classic maple syrup urine disease is ____ loss of enzyme activity. ___ and ___ are some residual enzyme activity. High dose of ____ (____), can be used for treatment of intermittent and mild presentations.
Complete
Intermittent
Mild
Thiamine (vitamin B1)
Branched chain keto acid dehydrogenase is regulated through ___ ___ of its E1 subunit, similar to pyruvate dehydrogenase.
Reversible phosphorylation
Branched chains amino acids and autism:
Branched chain alpha-keto acid dehydrogenase kinase (BCKDK) ____ and ____ alpha-keto acid dehydrogenase. In the three families with autism, loss of function in BCKDK was found.
Phosphorylates
Inactivates
Branched chain amino acids and autism.
Follow up studies point to ___ generation from the unconstrained branched chain ketoacid dehydrogenase (BCKDH) in the mitochondria of patients who lack ____ ____.
ROS
BCKDH Kinase (BCKDHK)
Phenylalanine and tyrosine:
The ____ of tyrosine is the first step in phenylalanine ____. Phenylalanine hydroxylase hydroxylase the ring, this reaction requires ____ as a redox cofactor.
Phenylalanine is both ___ and ____.
Synthesis
Degradation
Tetrahydrobiopterin
Ketogenic and gluconeogenic
Phenylalanine to tyrosine
Phenylketonuria (PKU) is caused by a defect in ____ ____ which prevents tyrosine biosynthesis. Phenylalanine accumulates in the brain and blood.
Phenylalanine hydroxylase
PKU
Symptoms:
Diagnosis:
Treatment:
In PKU, phenylalanine accumulates and is ultimately degraded to a ___ ___.
Phenyl ketone
PKU:
Excess phenylalanine interferes with the transport of ___ ____ amino acids (LNAAs) into the brain. This decreases the synthesis of ____ such as dopamine and serotonin.
Large neutral
Neurotransmitters
Non classical PKU:
Defects in Tetrahydrobiopterin metabolism such as ____ ____ deficiency, can mimic PKU.
Dihydropteridine reductase
Tyrosinemia Type II is a rare autosomal recessive mutation of ___ ___. Patients develop plaques on the hands and feet, corneal ulcers, and frequent mental retardation.
Tyrosine aminotransferase
Tyrosinemia Type II
Labs:
Treatment:
Tyrosinemia type III is the rarest form, caused by loss of function of _______ ____. Characteristic features are intellectual disability, seizures, and intermittent ataxia.
4-hydroxyphenylpyruvate dioxygenase
Alcaptonuria is a rare autosomal recessive deficiency in ____ ____. It was the first inborn error of metabolism to be described. Homogentisate accumulates and is excreted into urine. Patients are asymptomatic until middle age when they develop arthritis, back pain, and renal calculi.
Homogentisate oxidase
Diagnosis of Alcaptonuria:
_____ resulting from homogentisic acid deposition in a patient with Alcaptonuria
Ochronosis
Tyrosinemia type I is an inherited disorder of ____ ____ (FAH), results in accumulation of succinylacetone, leading to ___ ____. It is the most serious form.
Fumaryloacetoacetate hydrolase
Liver failure
Tyrosinemia type I
Presentation:
Diagnosis:
Treatment:
