Term
| What is the fate of the carbon core of amino acids in the fed state? |
|
Definition
| Energy storage as glycogen or triglycerides |
|
|
Term
| What is the fate of the carbon core of amino acids in the fasting state? |
|
Definition
| Energy production via pyruvate, acetyle CoA, acetoacetate, other TCA intermediates |
|
|
Term
| What is the most efficent form of energy storage in the body? |
|
Definition
| Triacylglycerols are by far the most efficent form of energy storage followed by proteins |
|
|
Term
| What amino acids are good sources of NADH and FAD(2H) independent of the TCA cycle via direct oxidation? |
|
Definition
| Valine, Isoleucine, and Leucine |
|
|
Term
| What are the essential amino acids that must be provided through the diet? |
|
Definition
| Histidine, Methionine, Threonine, Valine |
|
|
Term
| What amino acid(s) is produced from phenylalanine? |
|
Definition
|
|
Term
| What amino acid(s) is essential for adults but not for children? |
|
Definition
|
|
Term
| What amino acids are synthesized from glycolysis intermediates? |
|
Definition
| Glycine (from Serine), Cysteine (from Serine), Alanine (from Pyruvate) |
|
|
Term
| What amino acids are synthesized from oxaloacetate? |
|
Definition
| Aspartate and Asparagine (from Aspartate and Glutamine) |
|
|
Term
| What amino acids are synthesized from alpha-ketoglutarate |
|
Definition
| Glutamate, Glutamine (from Glutamate), Proline and Arginine (both from Glutamate) |
|
|
Term
| What is the coenzyme for transamination and deamination? |
|
Definition
|
|
Term
| What is the coenzyme in the metabolism of serine, glycine methionine, and histidine? |
|
Definition
|
|
Term
| Tetrahydrofolate is the conezyme for the metabolism of what amino acids? |
|
Definition
| Serine, Glycine, Methionine, Histidine |
|
|
Term
| Vitamin B12 is the coenzyme for the metabolism of what amino acid(s)? |
|
Definition
|
|
Term
| Hydroxylation of phenylalanine, tyrosine, and tryptophan requires what coenzyme? |
|
Definition
|
|
Term
| Tetrahydrobiopterin is the necessary coenzyme for the hydroxylation of what enzymes? |
|
Definition
| Phenylalanine, Tyrosine, and Tryptophan |
|
|
Term
| What is Tetrahydrobiopterin synthesized from? |
|
Definition
|
|
Term
| Vitamine B1 and lipoate are coenzymes for what reaction? |
|
Definition
| Oxidative decarboxylation of branched-chain amino acids |
|
|
Term
Oxidative decarboxylation of branched-chain amino acids requires what coenzyme(s)?
|
|
Definition
|
|
Term
| What amino acid is required for the growth of fast dividing leukemic cells? |
|
Definition
|
|
Term
| Asparinase is used to treat what? |
|
Definition
|
|
Term
| What is the primary methyl donor in the human body? |
|
Definition
| S-Adenosylmethionine (SAM) |
|
|
Term
| SAM participates in the synthesis of what compounds? |
|
Definition
| Phosphatidylcholine, Creatine, Carnitine, Melatonin, Epinepherin |
|
|
Term
| High levels of blood homocysteine is a risk factor for what? |
|
Definition
|
|
Term
| What deficiency is characterized by elevated blood methionine, homocysteine, and cystathione levels? |
|
Definition
|
|
Term
| What characterizes cystathionase deficiency? |
|
Definition
| Elevated blood methionine, homocysteine, and cystathione levels |
|
|
Term
| Cystathione synthase deficiency is characterized by what? |
|
Definition
| Elevated blood Methionine, Homocysteine levels, decreased Cystathione levels |
|
|
Term
Elevated blood Methionine, Homocysteine levels, decreased Cystathione levels is characteristic of what?
|
|
Definition
| Cystathionine Synthase Deficiency |
|
|
Term
| B12 deficiency is characterized by what? |
|
Definition
| Low blood Methionine, elevated blood Homocysteine, Cystathione |
|
|
Term
Low blood Methionine, elevated blood Homocysteine, Cystathione is characteristic of what?
|
|
Definition
|
|
Term
The following are symptomatic of what disease?
Elevated homocystine levels in blood
Elevated homocystine levels in urine.
Mental retardation or developmental delay.
Ectopialentis (dislocated lens)
Skeletal abnormalities (Marfan-like)
Increased clot formation, (risk factor for infarcts) |
|
Definition
|
|
Term
| What are the possible treatments for Homocysteinuria |
|
Definition
Dietary restriction of Met, and supplementation of Cys.
Vitamin B6 (PLP) supplementation (if responsive).
Vitamin B12 and folic acid supplementation (if responsive)
Betaine supplementation (methylation of homocysteine) |
|
|
Term
| What are the characteristics of Tyrosinemia I? |
|
Definition
| Toxic levels of fumarylacetoacetate, high levels of succinylacetone leading to rickets, elevated plasma tyrosine and phenylalanine, elevated plasma δ-aminolevulinic acid |
|
|
Term
| What causes Phenylketonuria (PKU)? |
|
Definition
| Phenylalanine Hydroxylase deficiency |
|
|
Term
| What causes phenylalanine hydroxylase deficiency? |
|
Definition
| Mutations in the enzyme, insufficient tetrahydrobioterin |
|
|
Term
| What is the recommended treatment for Phenylketonuria (PKU)? |
|
Definition
Phe-restricted, Tyr supplemented diet, avoid aspartame, artificial sweeteners |
|
|
Term
| What are the symptoms for Phenylketonuria (PKU) |
|
Definition
| Elevated phenylalanine in the blood and urine casuing a musty odor, neurological problems, hypopigmentation |
|
|
Term
| Tetrahydrobiopterin (BH4) is necessary for the hydroxylation of what amino acids? |
|
Definition
| Phenylalanine, Tyrosine, Tryptophan |
|
|
Term
| Alkaptonuria is caused by what? |
|
Definition
| Homogentisic acid oxidase deficiency in the Tyrosine degeneration pathway |
|
|
Term
| Homogenistic acid accumulation in the urine is symptomatic of what disease? |
|
Definition
|
|
Term
| What are the symptoms of Alkaptonuria? |
|
Definition
| Urine turns black when left standing for several hours, crippling arthritis |
|
|
Term
| Tyrosinase deficiency would cause what disease? |
|
Definition
| Oculocutaneous Albinism Type I |
|
|
Term
| Tyrosine is important in the synthesis of what neurotransmitters? |
|
Definition
|
|
Term
| What amino acids are involved in Maple Syrup Urine Disease? |
|
Definition
| I Love Vermont Maple Syrup = Isoleucine, Leucine, Valine, the branched chain amino acids |
|
|
Term
| What are characteristic symptoms of Maple Syrup Urine Disease? |
|
Definition
| Elevated branched-chain amino acids and branched chain keto-acids in the blood, maple syrup odor in urine and earwax, encephalopathy |
|
|
Term
| How is maple syrup urine disease managed? |
|
Definition
BCAA restricted high calorie diet. Usually BCAA-free formulas, supplemented with limited amounts of valine and isoleucine. Leucine is always the most restricted. |
|
|
Term
| What amino acids are transported to the brain through the blood-brain barrier via the same transporter? |
|
Definition
| Branched-chain Amino Acids, Phenylalanine, Tyrosine, Tryptophan, Histidine, and Methionine |
|
|
Term
| How is Glutamine utilized by the brain? |
|
Definition
| Converted to glutamate and GABBA |
|
|
Term
| How are neurological problems caused by Maple Syrup Urine Disease? |
|
Definition
| Leucine overload inhibits amino acid transporters of the blood brain barrier |
|
|
Term
| What are the primary products of Tryptophan metabolism? |
|
Definition
|
|
Term
| What is the result of dietary tryptophan and niacin (vit B3) deficiency? |
|
Definition
| Pellagra, characterized by Dermatitis, Diarrhea, Dementia, and ultimately DEATH. DUN DUN DUUUN! |
|
|
Term
| What Amino Acids undergo deamination as NH4? |
|
Definition
| Glycine, Serine, Threonine, and Histidine transfer their amino acid group to form Glutamate |
|
|
Term
| What amino acids undergo deamidation to remove the amide group as NH4? |
|
Definition
|
|
Term
| Where is deamidation important? |
|
Definition
|
|
Term
| What is the main pathway of amino acid nitrogen removal? |
|
Definition
| Transamination via the transfer of an amino group to a alpha-keto acid |
|
|
Term
| What is the amino acid generally collected on? |
|
Definition
|
|
Term
| What catalyzes transamination? |
|
Definition
|
|
Term
| What is the coenzyme for Transaminases? |
|
Definition
| Pyridoxal Phosphate (PIP) |
|
|
Term
| What is an essential component of PLP? |
|
Definition
|
|
Term
|
Definition
| Alanine Aminotransferase and Aspartate Aminotransferase |
|
|
Term
| What do high plasma levels ALT and AST indicate? |
|
Definition
|
|
Term
| Which is morespecific, AST or ALT? |
|
Definition
|
|
Term
| What has AST specifically been used to diagnose in the past? |
|
Definition
|
|
Term
| What fixes ammonia to alpha-ketoglutarate? |
|
Definition
| Glutamate Dehydrogenase + NADH/NADPH |
|
|
Term
| alpha-ketoglutarate fixed with ammonia produces what? |
|
Definition
|
|
Term
What fixes ammonia to glutamate?
|
|
Definition
| Glutamine Synthetase + ATP |
|
|
Term
| Glutamate fixed with ammonia produces what? |
|
Definition
|
|
Term
| What fixes ammonia to carbon dioxide? |
|
Definition
| Carbamoyl Phosphate Synthetase I + 2ATP |
|
|
Term
| CO2 fixed with ammonia produces what? |
|
Definition
|
|
Term
| What is the main ammonia detoxification reaction in the brain? |
|
Definition
| Glutamate + NH4 --> Glutamine via Glutamine Synthetase and 1ATP |
|
|
Term
| What are the functions of Glutamate? |
|
Definition
| Transamination of amino acids to collect nitrogen, providing NH4 to Urea via Deamination, Transaminating Oxaloacetate into Aspartate which can also provide NH4 to Urea |
|
|
Term
| Where does Urea synthesis take place? |
|
Definition
|
|
Term
| How is amino acid nitrogen transported to the liver? |
|
Definition
| Primarily Alanine, then Glutamine |
|
|
Term
| What are the main Alanine producers? |
|
Definition
|
|
Term
| What are the primary producers of Glutamine? |
|
Definition
|
|
Term
| Where does the Urea Cycle take place? |
|
Definition
| Begins in mitochondria, ends in cytosol |
|
|
Term
| What is the rate limiting step for the Urea Cycle? |
|
Definition
| Carbamoyl Phosphate Synthetase 1 (CPS1) |
|
|
Term
| Where does the rate limiting step for the Urea Cycle take place? |
|
Definition
| CPST1 takes place in the mitochondria |
|
|
Term
|
Definition
|
|
Term
| What allosterically activates CPS 1 and thus the Urea Cycle? |
|
Definition
|
|
Term
| CPS 1 deficiency is characteristic of what disease? |
|
Definition
|
|
Term
| What is the consequence of high levels of Arginine? |
|
Definition
| High N-acetyl-glutamate and increased Ornithine production leading to increased Urea production |
|
|
Term
| What catalyzes Citrulline Synthesis |
|
Definition
| Ornithine Transcarbamoylase |
|
|
Term
| Where does Citrulline synthesis take place? |
|
Definition
|
|
Term
| What transports Ornithine into the mitochondria for Citrulline synthesis? |
|
Definition
|
|
Term
| What disease is characterized by Ornithine Transcarbamoylase deficiency? |
|
Definition
|
|
Term
| What does Ornithine Translocase deficiency cause? |
|
Definition
| HHH Syndrome (Hyperornithemia, Hyperammonemia, Homocitrullemia) |
|
|
Term
| What catalyzes Arginosuccinate synthesis? |
|
Definition
| Arginosuccinate Synthetase |
|
|
Term
| Where does Arginosuccinate synthesis occur? |
|
Definition
|
|
Term
| What does Arginosuccinate synthesis require? |
|
Definition
|
|
Term
| What are the products of Arginosuccinate synthesis? |
|
Definition
| Aspartate via transamination of Oxaloacetate to be incorporated into Urea |
|
|
Term
| What does arginosuccinate synthetase deficiency cause? |
|
Definition
|
|
Term
| What catalyzes Arginin Synthesis? |
|
Definition
|
|
Term
| Where does Arginin Synthesis take place? |
|
Definition
|
|
Term
| What does arginosuccinate lyase deficiency cause? |
|
Definition
| Argininosuccinyl Acidemia |
|
|
Term
|
Definition
|
|
Term
| What does the cleavage of Arginine produce? |
|
Definition
|
|
Term
| Where does Arginine cleavage occur? |
|
Definition
|
|
Term
| What is the result of Arginase deficiency? |
|
Definition
|
|
Term
| What are the energetics of the Urea Cycle? |
|
Definition
|
|
Term
| How can energy be recovered from the Urea Cycle? |
|
Definition
| If Fumarate enters the TCA cycle |
|
|
Term
| When is Fumarate released in the Urea Cycle |
|
Definition
|
|
Term
| What kind of diet increases Urea synthesis? |
|
Definition
|
|
Term
| What body conditions increase Urea Synthesis? |
|
Definition
|
|
Term
| What causes Primary Hyperammonemias? |
|
Definition
| Defective enzymes in the Urea Cyle |
|
|
Term
| What causes Secondary Hyperammonemias? |
|
Definition
| Hepatic failure or genetic defects unrelated to urea cycle enzymes |
|
|
Term
| What is used to treat Hyperammonemias? |
|
Definition
| Low Protein Diet, Intravenous arginine HCL, amino acid Scavenger Drugs |
|
|
Term
| When is positive nitrogen balance normal? |
|
Definition
| During growth, pregnancy, lactation, or recovery from illness/malnutrition |
|
|
Term
| When is negative nitrogen balance normal? |
|
Definition
| During illness or malnutrition |
|
|
Term
| In what form are digestive proteases secreted? |
|
Definition
|
|
Term
| What activates Pepsinogen? |
|
Definition
|
|
Term
| What activates Trypsinogen |
|
Definition
| Enteropeptidase and Trypsin |
|
|
Term
| What activates Chymotrypsinogen, Proelastase, and Procarboxypeptidases? |
|
Definition
|
|
Term
| Metalloproteases specify for what amino acids? |
|
Definition
|
|
Term
| Aspartate proteases specify for what amino acids? |
|
Definition
| Phenylalanine, Leucine, Glutamate |
|
|
Term
| Serine Proteases specify for what amino acids? |
|
Definition
|
|
Term
| What causes Cystic Fibrosis? |
|
Definition
| Dried secretion the blocking pancreatic duct |
|
|
Term
| What causes chronic pancreatitis? |
|
Definition
| Loss of enzyme secreting pancreatic cells |
|
|
Term
| What is the treatment for cystic fibrosis and chronic pancreatitis? |
|
Definition
| Pancreatic Enzyme Supplement |
|
|
Term
| How are dietary amino acids uptaken from the intestinal lumen and from circulation? |
|
Definition
|
|
Term
| How are dietary amino acids released into circulation? |
|
Definition
| Bidirectional Fascilitated Transport |
|
|
Term
| How are di-peptides uptaken? |
|
Definition
|
|
Term
| What organs have similar amino acid transport systems? |
|
Definition
| Small intestines and the Kidney |
|
|
Term
| Elevated amino acid levels in the urine is indicative of what? |
|
Definition
| Amino acid absorption disease |
|
|
Term
| What is characteristic of Hartnup Disease? |
|
Definition
| Defects in neutral (hydrophobic) amino acids at the brush border |
|
|
Term
| What causes Hartnup Disease? |
|
Definition
| Autosomal Recessive, Dietary Tryptophan and Niacin (vit B3) deficiency |
|
|
Term
| What is characteristic of Cystinuria |
|
Definition
| Autosomal recessive, deficient brush border transport of COAL = Cystine, Ornithine, Arginine, Lysine (the basic amino acids) |
|
|
Term
| What symptoms indicate Cystinuria? |
|
Definition
| Hyperaminoaciduria, cystine stones in kidneys |
|
|
Term
| How is Cystinuria treated? |
|
Definition
| High fluid intake, medications to elevate urine pH |
|
|
Term
| What is characteristic of Lysinuric Protein Intolerance? |
|
Definition
| Autosomal recessive, defective basal transport of basic amino acids Lysine, Arginine, Ornithine |
|
|
Term
| What are the symptoms of Lysinuric protein intolerance? |
|
Definition
| Hyperaminoaciduria of basic amino acids, low plasma level basic amino acids, hyperammonemia following meals |
|
|
Term
| How is Lysinuric Protein Intolerance treated? |
|
Definition
| Intravenous arginine HCl and nitrogen scavenger drugs, protein restricted diet |
|
|
Term
| Lysosomal degradation is used for what kinds of proteins? |
|
Definition
| Endocytosed and phagocytosed protines, autophagy |
|
|
Term
| Ubiquitin-Proteasome degradation is used for what proteins? |
|
Definition
| Misfoled/damaged intracellular proteins, turnover of intracellular proteins |
|
|
Term
| What are the main proteases involved in extracellular matrix turnover? |
|
Definition
| Matric Metalloproteinases requiring Zinc |
|
|
Term
| What is the major lysosomal protease? |
|
Definition
|
|
Term
| What is used to mark proteins for degradation? |
|
Definition
|
|
Term
| Where is the machinery for ubiquitin taggin located? |
|
Definition
|
|
Term
| What determines which proteins will be ubiquitylated? |
|
Definition
| The ubiquitin ligase complex(E2-E3) |
|
|
Term
| What proteins are required for the activity of the Proteasome? |
|
Definition
|
|
Term
| What is the function of ATP in the proteasome? |
|
Definition
| Unfolding and threading into the core |
|
|
Term
| What is Bortezomib (Velcade)? |
|
Definition
Proteasome inhibitor drug used for treatment of multiple myelomas and mantle cell
lymphomas (diseases with elevated proteasome levels). |
|
|
Term
| What is characteristic of Angelman syndrome? |
|
Definition
| Mutation or deletion of the UBE3A gene that codes for the E3 subunit of ubiquitin ligase |
|
|
Term
| What is characteristic of Von Hippel-Lindau Syndrome? |
|
Definition
Deficiency in an E3 ubiquitin ligase subunit (VHL) prevents the destruction of hypoxia inducible factor 1a (HIF1a), a transcription factor that promotes angiogenesis. |
|
|
Term
| What is the specialized storage unit for amino acids? |
|
Definition
|
|
Term
| What is the main function of the Blood Amino Acid Pool? |
|
Definition
To traffic amino acids between tissues for the production of biomolecules, energy or waste products (urea) |
|
|
Term
| Through what structure are most amino acids transported to the liver? |
|
Definition
|
|
Term
| What structure uses the vast majority of Glutamine? |
|
Definition
|
|
Term
| What produces acute phase proteins? |
|
Definition
|
|
Term
| What is the effect of Ammonia encephalopathy? |
|
Definition
|
|
Term
| Why do kidney stones appear in cystinuria? |
|
Definition
| slow solubility of cysteine |
|
|
Term
| Source of 1st nitrogen in urea cycle? |
|
Definition
|
|
Term
| What is the major transporter of amino groups from muscle to liver? |
|
Definition
|
|
Term
| Why are Homocystinuria patients given vitamin B12? |
|
Definition
|
|
Term
| Metabolism of carbon skeletons of ketogenic AA leads to production of what? |
|
Definition
|
|
Term
| What are the major transporters of amino groups between various tissues/liver |
|
Definition
|
|
Term
| What amino acid is nonessential in adults but essential in animals? |
|
Definition
|
|
Term
| Phenylketonuria seizures are due to what? |
|
Definition
Lowered level of other aromatic AAs in the brain |
|
|
Term
| What is Heme synthesized from? |
|
Definition
|
|
Term
| What is heme used to synthesize in hepatocytes? |
|
Definition
|
|
Term
What is heme used to synthesize in bone marrow?
|
|
Definition
|
|
Term
| What is the rate limiting reaction in the synthesis of Heme? |
|
Definition
| d-Aminolevulinic Acid Synthase (d-ALA) |
|
|
Term
| What is the cofactor of d-Aminolevulinic Acid Synthase? |
|
Definition
|
|
Term
| What catalyzes d-ALA synthesis? |
|
Definition
| ALA synthase via condensation of glycine and succinyl-CoA |
|
|
Term
| What does d-ALA synthesis require? |
|
Definition
|
|
Term
| Where is the gene (ALAS2) for d-ALA synthase expressed in RBC precursors located? |
|
Definition
|
|
Term
| Where is the gene (ALAS1) for d-ALA synthase expressed throughout the body located? |
|
Definition
|
|
Term
| What causes X-linked Sideroblastic Anemia? |
|
Definition
| Mutations in the ALAS2 gene for d-ALA synthase |
|
|
Term
| What allosterically inhibits d-ALA synthase? |
|
Definition
|
|
Term
| What is the result of drugs being oxidized by Cytochrom P450? |
|
Definition
| Increased heme consumption leading to increased d-ALA synthase synthesis |
|
|
Term
| What catalyzes Pyrrole Ring Synthesis? |
|
Definition
| d-ALA Dehydratase via condensation of two d-ALA |
|
|
Term
|
Definition
| Inhibits d-ALA dehydratase, d-ALA accumulates |
|
|
Term
| Which is an important intermediate in Heme synthesis? |
|
Definition
|
|
Term
| What is the final step in Heme synthesis? |
|
Definition
| Spontaneous introduction of Fe2+ into protoporyphin IX |
|
|
Term
| What enhances the incorpration of Fe2+ into protoporyphin IX? |
|
Definition
|
|
Term
| What inhibits ferrochelatase? |
|
Definition
|
|
Term
|
Definition
| Inherited defects in heme synthesis leading to excess porphyrin accumulation and excretion |
|
|
Term
| Porphyrias are autosomal dominant except when? |
|
Definition
Erythropoetic protoporphyria: recessive, caused by eficiency of ferrochelatase
X-linked dominant protoporphyria: cause by gain of function mutation in ALA2 gene
|
|
|
Term
| Are hepatic porphyrias usually acute or chronic? |
|
Definition
|
|
Term
| Are Erythropoetic Porphyrias usually acute or chronic? |
|
Definition
|
|
Term
| How are Porphyrias treated? |
|
Definition
|
|
Term
| What is Porphyria Cutanea Tarda (PCT)? |
|
Definition
| Most common subtype of Porphyria causing photosensitivity due to porphyrins under skin which are phototoxic upon activation by light |
|
|
Term
| What enzyme is affected in X-linked protoporphyria? |
|
Definition
|
|
Term
| What enzyme is affected in Acute Intermittent Porphyria? |
|
Definition
| Hydroxymethylbilane synthase |
|
|
Term
What enzyme is affected in Porphyria Cutanea Tarda
|
|
Definition
| Uroporphyrogen decarboxylase |
|
|
