Chapter 30: AA Metabolism V Flashcards
What are the products of tryptophan degradation?
Products:
Kynurenine: immune cell func, psychiatric/inflammatory effects (used to make Niacin, Vit B3)
Formate (HCOO-): can be conjugated to THF (1 C carrier)
What vitamin is derived from Kynurenine?
Kynurenine can form Niacin (Vitamin B3)
Niacin can be used to make Nicotinamide monophosphate (coenzyme), NADP, or NAD+
What hormones is tryptophan used to make?
Melatonin and Serotonin
What three amino acids are used as substrates in branched-chain amino acid (BCAA) degradation? What are the products?
Substrates: Isoleucine Leucine Valine (I Love Vermont Maple Syrup)
Products: Propionyl CoA, Acetoacetyl CoA (—> acetyl CoA)
What AA’s are propionyl CoA derived from in BCAA degradation? What is propionyl CoA used for?
AA’s: Isoleucine, Valine
**propionyl CoA can also be produced through methionine degradation OR odd chain FA degradation
Propionyl CoA is used for odd chain FA metabolism after being converted into succinyl CoA
What AA is acetyl CoA derived from in BCAA degradation?
Leucine —> Acetoacetyl CoA —> Acetyl CoA
What is the key enzyme in BCAA AA degradation? What does it require?
Branched-chain ketoacid (BCKA) dehydrogenase
“Tender Loving Care Feels Nice”: Thiamin (B1), Lipoic acid, CoA (pantothenate, B5), FAD+ (riboflavin, B2), NAD+ (niacin, B3)
**also req for PDH and alpha-ketoglutarate DH
**transketolase: only requires thiamine
What results from BCKA DH (branched-chain ketoacid DH) deficiency? Pattern of inheritance, most common area, symptoms, tx?
Maple Syrup Urine Disease (MSUD):
-POI: autosomal recessive
-area: Lancaster, PA (mennonite)
-symptoms: Urine has a maple sugar odor
-Tx: reduced BCAA intake
Deficiency of what (2 possibilities) causes methylmalonic aciduria/acidemia due to a buildup of methyl malonic acid and propionic acid? What does this cause in individuals?
Enzyme deficiency: Methyl Malonyl CoA mutase
Coenzyme deficiency: Cobalamin (Vitamin B12) **required for methyl malonyl CoA mutase
Causes metabolic acidosis and mental retardation
what reaction does methyl malonyl CoA mutase catalyze?
L-methyl malonyl CoA —> succinyl CoA (enters TCA cycle)
In histidine metabolism, what converts histidine to urocanate? Where does this occur?
Enzyme: Histidase
Location: SKIN and Liver (where complete metabolism occurs)
What is one component of sweat that is made from Histidine metabolism?
Urocanate
in histidine metabolism, what cofactor is required for the reaction from N-formamino glutamate to form the products? what are the two products?
cofactor: THF/tetrahydrofolate (Vit B9 derivative)
products: glutamate, N5-formamino THF (used in nucleotide synthesis)
What enzyme deficiency causes histidinemia?  how is this tested for?
enzyme deficiency: histidase
**histidase is expressed in the liver and skin
test: skin biopsy to check for histidase deficiency
what are the two products that can be made from lysine metabolism?
- Acetacetyl CoA
- Carnitine: required for beta oxidation of FA’s
*** In order to produce carnitine, it is methylated 3x using methyl transferase/SAM 
what are the substrates and products of creatine synthesis?
substrates: Glycine, Arginine
product: creatine —> phosphocreatine (holds onto phosphates for energy storage in sk/cardiac muscle, brain)
what is needed to convert creatine to phosphocreatine?
ATP
what are the three parts of folic acid (structure)? What vitamin is it?
- Pteridine ring: contains N5
- PABA (para amino benzoic acid): contains N10
- Polyglutamate
Folic acid = Vitamin B9 (essential)
Substrate used for folic acid synthesis? Who can synthesize folic acid?
substrate: PABA (and pteridine precursors)
synthesized by: microorganisms in the gut (PABA —> folic acid)
***HUMANS CANNOT SYNTHESIZE FOLIC ACID
What inhibits folic acid synthesis?
SULFAMETHOXAZOLE or sulfoamides (anti-microbial)
what enzyme is used for the conversion of dihydrofolate (DHF) —> tetrahydrofolate (THF)? What inhibits this conversion?
enzyme: dihydrofolate reductase (requires NADPH)
inhibited by: trimethoprim (prokaryotes) or methotrexate (eukaryotes)
2, 3, 4 (mnemonic): DIhydrofolate —x TRImethoprim x—> TETRAhydrofolate
what is formed when 1C units are added to tetrahydrofolate (THF) aka THF is “charged” with 1C units?
product: ACTIVE folate (formyl THF, methenyl THF, methylene THF)
Where are the 1C units derived from? (4 different sources)
- tryptophan degradation (formyl)
- histidine degradation (methenyl)
- serine/glycine degradation (methylene)
- CH2 reduction (methyl)
What can formyl THF, methenyl THF and methylene THF all be used for?
purine and thymidine synthesis
