Exam 2 AA metabolism pt 2 Flashcards
Name two linear compounds in the proline biosynthetic pathway.
Glutamate, Gultamate semialdehyde
What are the functions of hydroxyprolines?
They are important in stabilizing the triple helix of collagen
Name the amino acid that is required for selenocysteinyl tRNA synthesis.
Serine (attached to tRNA as Seryl-tRNA)
What is the cofactor that is required for the phenylalanine hydroxylase reaction?
Tetrahydrobiopterin (THB)
What enzyme deficiency causes phenylketonuria (PKU)?
Phenylalanine hydroxylase
Name two disorders of tyrosine metabolism.
Alcaptonuria, Albinism, PKU
What enzyme deficiency causes albinism?
tyrosinase
Methionine adenosyltransferase catalyzes the synthesis of ______?
S-adenosylmethionine (SAM)
What compound is the precursor for cystine synthesis?
Methionine
Name a disorder of cystine metabolism.
Homocystinuria
Name the oxidized form of homocysteine.
homocystine
Name the amino acid precursor for NMP synthesis
Tryptophan
Name an enzyme that requires a vitamin B12 derivative as a coenzyme.
Methionine synthase (in converting homocysteine to methionine)
Mutase (converting propionyl CoA to Succinyl CoA)
Name the pathway that requires both the derivatives of vitamin B12 and another of vitamin B.
Catabolism of branched chain amino acids (BCAA’s) into succinyl CoA:
Leucine, Valine, Isoleucine are transaminated with vitamin B derivative [Lip. 234, 249]
Successive reactions of oxidative decarboxylation and dehydrogenation can lead to Propionyl CoA [Lip. 249]
Propionyl CoA is isomerized into succinyl CoA with mutase and a vitamin B12 derivative. [Lip. 326]
Additionally, carboxylase reactions require Biotin (another B-complex derivative)
Name a disorder of a branched chain amino acid metabolism.
Maple syrup urine disease. (MSUD)
Name the amino acid that is required for carnitine biosynthesis.
Lysine
Name the amino acids that are required for creatine synthesis.
glycine and arginine
Name 4 functional groups that can be added to tetrahydrofolate.
Formyl
Methenyl
Methylene
Methyl
They are attached to the N5 or N10 active centers.
Name the amino acid and the vitamin derivative that is required for glycine synthesis.
Serine and THF [Lip. 325]
Name the 2 degradative pathways that require tetrahydrofolate.
Histidine → Glutamate [L. 247]
Resynthesis of methionine from homocysteine [L. 249, Venk Amino Acid metabolism lecture 4]
Also involved in the degradation of tryptophan
Name two reactions that require tetrahydrobiopterin as a cofactor.
Phenylalanine + O2 → Tyrosine + H2O
(Phenylalanine hydroxylase & THB)
Arginine + O2 + NADPH → NO + Citrulline
(Nitric oxide synthase & THB)
- Describe how homocysteine is converted into methionine
Homocysteine → Methionine
(Vit B12 derivative & Methionine synthase)
Lysine is required for synthesis of _______?
carnitine
Name the components of folate
Pterin, PABA and Glutamic Acid
Name the 2 degradative pathways that require tetrahydrofolate.
Histidine → Glutamate [L. 247]
Resynthesis of methionine from homocysteine [L. 249, Venk Amino Acid metabolism lecture 4]
Also involved in the degradation of tryptophan
Name the vitamin derivative that is required for the prolyl hydroxylase reaction.
vitamin c
Why is the element selenium is essential?
Selenium is used to synthesize selenocysteine. Selenocysteine is part of
glutathione peroxidase, which is important to prevent oxidative damage.
phenylketonutia
Normally, phenylalanine is converted to tyrosine via phenylalanine
hydroxylase. This reaction requires THB (tetrahydrobiopterin).
■ Defect in phenylalanine metabolism due to deficiency of phenylalanine
hydroxylase will lead to phenylketonuria.
phenilanaline accumulates and gets excreted as
phenylpyruvate and phenylketone
PKU is a defect in ???
phenylalanine metabolism, NOT
tyrosine metabolism.
homocystinuria (2nd type)
Deficiency in cystathionine betasynthase
alcaptonuria
Normally, during tyrosine metabolism, the intermediate homogentisic acid
gets converted to maleyl acetoacetate via homogentisate oxidase.
■ Deficiency in homogentisate oxidase→ accumulation of homogentisic
acid → homogentisic acid is oxidized into a dark brown polymer →
polymer is deposited in joints → arthritis
albinism
Normally, tyrosine is used to synthesize melanin via tyrosinase.
■ Deficiency in tyrosinase → defective melanin production → skin
susceptible to damaging effects of sunlight such as skin cancer.
in homocystinyria accumulation of what ??? what forms
accumulation of homocysteine >
● excreted in the urine
● form homocysteine thiolactone a very reactive intermediate
that thiolates LDL, which aggregates & forms atheromas.**
importance of homocysteine
2 homocysteinecan be linked together via disulfide bond to
form homocystine (oxidized form)**
○ causes skeletal abnormalities, thrombosis & mental
retardation
**Homocystinuriacan also manifest if there is a deficiency in:
methionine synthase
● vitamin B12
● N5CH3THF deficiency
● In this case, homocysteine canNOTbe used to reconverted
into methionine
● lack of methionine → impaired SAM synthesis and associated
methylations.
maple urine disease /defficiency in enzyme
Normally, the catabolism of branched chain amino acids (valine, leucine,
isoleucine)requires the enzyme BCKA (branched chain keto acid)
dehydrogenase.
■ Deficiency in BCKA dehydrogenasecauses the branched chain amino
40
acids to accumulate and in the urine, making urine smells like maple
syrup → maple syrup urine disease
■ Therapy: reduced consumption of branched chain amino acid in the diet.
■ genetic frequency of MSUD worldwide: 1 in 185,000 newborns
■ genetic frequency of MSUD in the inbred Mennonite population of
Lancaster County, PA is 1 in 175 ***newborns.
Histinidemia
Normal metabolism of histidine requires histidase,which converts
histidine to urocanate. Histidase is highly expressed in skin and liver. In
skin, urocanate is one of the components of sweat. The complete
catabolism of histidine happens only in the liver.
■ Deficiency of histidase → histidine accumulation in blood → histidinemia.
Histidase deficiency can be confirmed using skin biopsies.
can folate acid be synthesized by humans
No because humans lack the enzyme that converts PABA into folic acid.
What step is inhibited by sulfamethoxazole?
PABA → Folic acid
- Describe in detail, the role of folate in relation to one carbon metabolism.
Folate (folic acid) is used to make THF.
○ THF can act as a carrier of carbon atoms.
○ One carbon metabolism involves the transfer of onecarbon groups such
as formyl, methenyl, methylene, or methyl groupsto THF form formylTHF,
methenylTHF, methyleneTHF, or methylTHF.
without folic acid whats impaired
impaired synthesis of purine, thymidine, and methionine.
- Describe the biosynthesis of carnitine.
SAM provides methyl (CH3) groups.
○ Methyl transferase transfers three methyl groups from 3 SAMs to lysine to form
Ntrimethyl lysine & 3 homocysteine. Through additional steps, Ntrimethyl lysine
is converted to carnitine.
What are some organism specific dihydrofolate reductase (DHFR) inhibitors?
Epiroprim (a type of trimethoprim)
○ Pyrimethamine
○ Methotrexate
- Trimethoprim, methotrexate and pyrimethanimine inhibits ____ (specify the organisms).
trimethoprim inhibits bacterial DHFR; does not affect human
○ pyrimethanimine inhibits protozoan (ameoba) DHFR; does not affect human
○ methotrexate inhibits eukaryotic DHFR; affects human
