Protein Metabolism Flashcards
1
Q
What is the amino acid pool supplied and depleted by? (3 each)
A
Supplied:
- protein turnover
- digested food
- de novo syn of nonessential amino acids
Depleted:
- prod of body protein
- syn of nitrogen-containing compounds
- degradation
2
Q
- autosomal recessive condition that is associated w/ defects in protein transporters
- defective transport of nonpolar or neutral AAs (e.g. tryptophan), leads to elevated conc in the urine
- transporter located in kidney and small intestine
- manifests in infancy w/ failure to thrive, nystagmus, tremor, intermittent ataxia, and photosensitivity
A
Hartnup disease
3
Q
- autosomal recessive condition that is associated w/ defects in protein transporters
- defective transport of dimeric cystine and dibasic AAs: Arg, Lys, and ornithine (COAL)
- formation of cystine crystals in kidneys (renal calculi)
- patients present w/ renal colic, abd pain that is intermittent and is similar to kidney stone pain
A
cystinuria
4
Q
AA biosyn
- member: aromatic = Trp, Tyr
- summary:
A
Phe > Tyr
Ribose 5-phosphate > His
5
Q
AA biosyn
- member: serine = Ser, Cys, Gly
- summary:
A
3-phosphoglycerate > Ser > Cys or Gly
6
Q
AA biosyn
- member: pyruvate = Ala
- summary:
A
Pyruvate > Ala
7
Q
AA biosyn
- member: Aspartate = Asp, Asn
- summary:
A
Oxaloacetate > Asp > Asn
8
Q
AA biosyn
- member: Glutamate = Glu, Gln, Pro, Arg
- summary:
A
α-ketoglutarate > Glu > Gln, Pro, Arg
9
Q
- type of proteolytic enzyme
- attacks at C- (carboxypeptidase) or N-terminus (aminopeptidase) ends
- digests terminal peptide bonds to release amino acids
A
exopeptidase
10
Q
- type of proteolytic enzyme
- attacks within the protein at a specific site, described more specifically by MOA which is dependent on catalytic enzyme in active site
- digests internal peptide bonds
A
endopeptidase
11
Q
- type of intracellular proteolytic control mechanism
- sequester >50 hydrolase-type intraceullar proteolytic enzymes
- active at pH 5, inactive at pH 7
- non-selective
- 3 types: macro, micro, and chaperone mediated (CMA)
A
lysosomal / autophagy
12
Q
- type of intracellular proteolytic control mechanism
- large ______ cytoplasmic complex that cleaves polyubiquinated proteins > ubiquitin pathway
- proteins are degraded to peptides and amino acids, which go to different pathways (biosyn, disposal, glucose/glycogen syn, FA syn, and cell respiration)
A
proteasome
13
Q
What is the extracellular mechanism of proteolysis?
A
- proteolytic enzymes secreted as inactive zymogens, which are activated by proteolytic cleavage
- inactive trypsinogen and chymotripsinogen are released into SI lumen
- trypsinogen activated by enterokinase which creates trypsin
- trypsin activates chymotrypsinogen and other molecules of trypsinogen
14
Q
What are the ketogenic amino acids? (2)
A
- Leu
- Lys
(acetyl CoA or acetoacetate)
(precursors for α-keto acids, ketone bodies, and FA’s)
15
Q
What are the amino acids that are both ketogenic and glucogenic? (5)
A
- Ile
- Trp
- Phe
- Tyr
- Thr
16
Q
What are the glucogenic amino acids? (13)
A
- Val
- His
- Arg
- Asn
- Gln
- Met
- Ala
- Asp
- Glu
- Gly
- Pro
- Ser
- Cys
(pyruvate or TCA cycle intermediates (OAA, α-ketoglutarate, succinyl CoA, fumarate)
(precursors for glucose syn via gluconeogenesis)
17
Q
- enzymes that shuffle amino groups
- amino group is transferred to an α-ketoacid
- couple rxns
- require coenzyme: pyridoxyl-5’-phosphate (PLP) (derivative of vit B6)
- clinical relevance: ALT and AST liver enzymes
A
transaminases / aminotransferases
18
Q
How are the branch chain amino acids (Val, Ile, Leu) metabolized?
A
- reduced to intermediates via branched-chain amino acid aminotransferases
- reduced to isobutyryl CoA (Val), α-methyl-butyryl CoA (Ile), and isovaleryl CoA (Leu) by branched-chain α-keto dehydrogenases (needs CoA, FAD, lipoic acid, NAD, TPP); this is where maple syrup urine disease may occur if there is deficiency in these enzymes or co-enzymes
- reduced to methacrylyl CoA (Val), tiglyl CoA (Ile), and β-methylcrotonyl CoA (Leu) by acyl CoA dehydrogenases (FAD linked)
- methacrylyl CoA (Val) converted to propionyl CoA, tiglyl CoA (Ile) converted to propionyl CoA and acetyl CoA; the propionyl CoA then converted to methylmalonyl CoA and then succinyl CoA
- meanwhile: β-methylcrotonyl CoA (Leu) converted to HMG CoA, then acetyl CoA and acetoacetate
19
Q
- vitamin deficiencies (B6, B12, folic acid) or genetic defects in enzymes (cystathionine β-synthase) cause defective metabolism of homocysteine
- risk factor for atheroslerotic heart dz, stroke, thrombosis, and can result in neuropsychiatric illness (vascular dementia, Alzheimer’s)
- other risks: eye lens dislocation, myopia, osteoporosis, unproportional growth, chest wall deformities, altered facial appearance, mental retardation
- vit supplementation can normalize plasma homocysteine levels in some cases
A
hyperhomocysteinemia and homocystinuria
20
Q
- rate autosomal disease resulting from deficient branched-chain α-keto acid dehydrogenase complex (BCKD) activity which results in brached-chain ketoaciduria
- BC AA’s in urine give hallmark sweet urine smell
- also accumulate in blood, causing toxic effects and eventual mental retardation
- tx: synthetic diet limiting BCAA’s (Val, Ile, Leu)
- BCKD activity may be restored w/ thiamine supps in mild forms of condition
- death usually within 5 months of birth based upon classification
- higher in Mennonite, Amish, and Jewish populations
A
maple syrup urine disease
21
Q
What is the general metabolism of Phe?
A
- Phe is converted to Try by phenylalanine hydroxylase (phenylketonuria)
- Tyr > p-hydroxyphenylpyruvate (tyrosinemia type II)
- p-hydroxyphenylpyruvate > homogentisate (tyrosinemia type III)
- homogentisate > maleylacetoacetate (alkaptonuria)
- maleylacetoacetate > fumarylacetoacetate
- fumarylacetoacetate > fumarate and acetoacetate (tyrosinemia type I)
22
Q
- caused by defects in activity of phenylalanine hydroxylase (PAH)
- most common IEM, first to be included in newborn screening (post-parturition Guthrie heel prick test)
- Phe converted to phenylpyruvate and then phenyllactate (musty odor in urine) and phenylacetate
- later two disrupt neurotransmission, block AA transport to brain, myelin formation, results in severe brain function impairment
- tx: dietary limit of Phe, synthetic protein supplemented w/ Tyr
- secondary form of condition results from tetrahydrobiopterin deficiency (cofactor of PAH), defects in syn or regeneration of BH4
A
phenylketonuria
23
Q
derivative of Ser
A
acetylcholine
24
Q
derivative of Glu
A
- γ-aminobutyric acid (GABA)
25
Q
Derivatives of Tyr (3)
A
- dopamine > norepi > epi (Parkinsonism)
- thyroid hormones > triiodothyronine (T3) and thyroxine (T4) (Graves’ dz, hyper/hypothyroidism)
- melanin (albinism)
26
Q
Derivatives of Trp (2)
A
- serotonin > melatonin (deficiency in conversion of Trp to serotonin could lead to carcinoid tumors)
- Trp (needs vit B6) > niacin > NAD+/NADP+
27
Q
- due to severe lack of melanin
- conversion of tyrosine to melanin is blocked due to defects in enzyme tyrosinase
- results in partial or complete absence of pigmentation in skin, hair, and eyes
A
albinism
28
Q
- 660 kDa portein made by thyroid and used to prod T4 and T3
- has ~120 Tyr residues, some labeled with iodine (mono and diiodinated Tyr)
- T4: combo of 2 diiodinated Tyr
- T3: combo of 1 monoiodinated and 1 diiodinated Tyr (more potent than T4 but shorter half-life)
- hyperthyroidism tx: carbimazole and propylthiouracil block iodination of thyroglobulin to decrease prod of T4 and T3
A
thyroglobulin and thyroid hormones
29
Q
How is nitrogen removed in the body?
A
- nitrogen in form of ammonia is removed as Glu and Gln in brain (glutamine synthase) and removed as Glu in other tissues
- nitrogen in the form of urea is generated in AA metabollic pathways by deamination mechanisms
30
Q
How is ammonium removed from the brain?
A
- α-KG > Glu (glutamate dehydrogenase)
- Glu > Gln (glutamine synthase)
- Gln transported via BS to liver
- Gln in liver > Glu (glutaminase)
- excess ammonium excreted via urea cycle
31
Q
How is excess ammonium removed from muscle?
A
- pyruvate > α-KG and Ala (by ALT)
- Ala transported via BS to liver
- Ala in liver > pyruvate which goes into gluconeo to form glucose (by ALT)
- Ala and α-KG also condensed in liver to Glu
- ammonium removed from Glu to form α-KG (by GLDH)
- excess ammonium excreted via urea cycle
32
Q
What are the general steps of the urea cycle?
A
- NH4+ > carbamoyl phosphate (carbamoyl phosphate synthetase - rate limiting)
- phosphate group removed from carbamoyl, carbamoyl condensed w/ ornithine to form citrulline (ornithine transcarbamoylase)
- citrulline leaves mito and enters cyto
- citrulline condensed w/ Asp > arginino-succinate (argininosuccinate synthetase, uses ATP)
- arginino-succinate > Arg and fumarate (arginosuccinate lyase)
- Arg > ornithine and urea (arginase, inhibited by ornithine)
- cycle continues with ornithine conversion to citrulline
- urea sent via BS to kidneys to be excreted
33
Q
What is the condition associated with defect in ornithine transcarbamoylase (enzyme that condenses carbamoyl and ornithine to form citrulline)?
A
hyperammonemia w/ orotic aciduria (X-linked)
34
Q
- excessive ammonia due to disorders in urea cycle or liver failure
- NH3 is toxic agent due to its ability to permeate membranes
- causes pH imbalance, astrocyte swelling, cerebral edema, intracranial hypertension
- glutamate dehydrogenase catalyzes ox deamination of glutamate to α-KG, key reactant in TCA; inhibits activity of TCA cycle (disrupts ATP prod)
- postsynaptic excitatory proteins are inhibited which depresses CNS function
- depletion of glutamate disrupts neurotransmitter activity (key reactant in form of GABA)
- also causes mito dysfunction
A
ammonia toxicity
35
Q
- urea production is increased by a ____ ______ diet and decreased by ____ ____ diet
- insulin and glucagon play a role in urea production
- 20-30% of urea prod is hydrolyzed in GI tract by bacterial urease
- provides nitrogen source for gut bacteria, salvage, and reuse
- ____ ______ diet enhances prod and hydrolysis
A
- high protein, high carb
- high protein
