Protein and AA metabolism Flashcards
Hartnup Disease
Defects in AA reabsorption -> Cystinuria
Exopeptidase
attacks at C terminus or N terminus ends
Endopeptidase
Attacks within the protein at a specific site
Intracellular proteolytic control
via large proteasome that cleave polyubiquinated proteins.
Extracellular proteolytic control
Proteolytic enzymes secreted as needed. First secreted as inactive zymogens, that are activated by proteolytic cleavage -> ex. inactive trypsinogen and chymotrypsinogen are released into the SI lumen. Trypsinogen is activated by enterokinase and then activated trypsin activates chymotrypsinogen into chymotrypsin.
Essential AA
TIM HRKL VFWQ
Ketogenic AA
Leu and Lys
Ketogenic and Glucogenic
Ile, Trp, Phe, Tyr, Thr
Glucogenic AA
His, Met, Gly, Val, Arg, Ala, Pro, Asn, Asp, Ser, Gln, Glu, and Cys
Common precursors of AA
OAA -> D Pyruvate -> A, V, L Ribose 5 P -> H 3 -PG -> S å KG -> E PEP + Erythrose 4P -> F
AA that can enter TCA cycle and where?
F, Y, D -> Fumarate
M, V, T, I -> Propionyl CoA -> Succinyl-CoA
Q, P, H, R -> E -> å ketoglutarate
Function of transaminases and cofactor
transfer amino group from AA to an å-ketoacid and require pyridoxyl 5-P (B6)
Removal of amino group from Glutamate generates å -KG via 3 mechanisms
- ) oxidation deamination by glutamate dehydrogenase which releases ammonium ion
- ) transfer of Amino group to pyruvate by ALT
- ) transfer of amino group to OAA by AST
Homocystinuria
Deficiency in cystathione B-synthase leads to buildup of homocysteine, which can accumulate and be excreted in urine.
Where are BCAs degraded?
BCAs are not degraded in liver due to the absence of the required aminotransferase. Instead they are degraded mainly in muscle, kidney, and brain.
Consequences of hyperhomocysteinemia and homocystinuria
Vitamin deficiencies of (B6, B12, and folic acid) or genetic defects in the enzyme cystathionine ß-synthase cause defective metabolism of homocysteine and can lead to heart disease and stroke, mental retardation.
Maple syrup urine disease
AR disease resulting from deficient branched-chain å-keto acid dehydrogenase complex (BCKD). BCAs present in urine, which give hallmark of maple syrup smell. Higher in mennonite, amish, and jewish populations.
Phenylketonuria (PKU)
deficiency in phenylalanine hydroxylase. Phe instead is converted to phenyllactate and phenylacetate, resulting in severe impairment of brain function.
Trp derivatives
Ser derivatives
Tyr derivatives
Glu derivatives
Trp: serotonin -> melatonin and Niacin -> NAD
Ser: Acetlycholine
Tyr: Dopamine -> Norepi -> Epi., Thyroid hormones, Melanin
Glu: GABA
Albinism and Tyrosinase
Albinism is due to lack of melanin. Conversion of tyrosine to melanin is via tyrosinase. Blocking of this enzyme results in partial or complete absence of pigmentation in skin.
Thyroglobulin and Thyroid hormones
Thyroglobulin is made from thyroid and has over 120 tyrosine residues.
Ammonia removal in brain vs ammonia removal in other tissues
Glu -> Gln in brain and then Gln -> Glu in liver and NH4+ enters urea cycle
Ala -> pyruvate with å KG -> Glu and NH4+ enters urea
Hyperammonemia w/ Orotic aciduria
X-linked recessive defect of ornithine transcarbamoylase.
Ammonia toxicity
excessive ammonia due to disorders in the urea cycle or liver failure can have highly toxic effects on the brain and CNS.
