Amino Acids, Proteins and Disorders Flashcards
maple syrup urine disease?
- can’t break down Val, Leu, Ile (branched chain AAs)
- no branched-chain ketoacid dehydrogenase
- progressive from infancy: lethargy, weight loss, hyper/hypotonia, MR, urine smells like maple syrup
PKU (phenylketonuria)?
- can’t break down Phe –> too much
- no phenylalanine hydroxylase –> needs tyrosine supplementation
- decrease in tetrahydrobiopterin cofactor
- MR, microcephaly, musty odor of sweat/urine
- restrict Phe and aspartame in diet; esp. for pregnant mother
alkaptonuria?
- can’t break down homogentisic acid (tyrosine/Phe breakdown product)
- no homogentisate oxidase
- arthritis (ochronosis cartilage accumulation) prior to 3rd decade; urine darkens upon sitting in air, dark sclera
Hartnup’s Disease?
- no neutral AA transporter –> decrease in tryptophan absorption
- pellagra due to niacin deficiency (made from tryptophan)
homocystinuria?
- methionine degradation pathway not working –> can’t break down homocystinuria
- Causes: cystathione synthase (CS) deficiency; decreased affinity of CS for Vit. B6 (pyridoxal phosphate); homocysteine methyltransferase deficiency; lack of folate, B6, B12 in diet (less severe)
- vessel damage (DVT, MI, atherosclerosis), MR, downward lens disloations, homocystinuria
- Tx: decrease Met intake, increase intake of Cys, B12, folate, B6 (in case of decreased CS affinity for B6)
propionyl-CoA carboxylase/methylmalony-CoA deficiency
- can’t handle Val, Met, Ile, Thr in propionic acid pathway
- ketoacidosis
- p-CoA carboxylase deficiency: increased propionic acid, methyl citrate, hydroxypropionic acid
- mm-CoA deficiency: increased methylmalonic acid
- restrict Val, Met, Ile, Thr in diet
What bacterial toxins inhibit elongation factor-2 (EF-2) in protein synthesis and how?
-ADP-ribosylation by toxins from Pseudomonas and Diphtheria
What drug(s) bind to the 30S unit of the prokaryotic ribosome? The 50S unit? What do they do exactly?
- Aminoglycosides bind 30S - prohibit initiation complex formation/promotes mRNA misreading
- Chloramphenicol binds 50S - inhibits peptidyl transferase
- Macrolides bind 50S - inhibits translocation
- Clindamycin binds 50S - inhibits translocation
How does the deltaF508 CFTR mutation result in the lack of CFTR in cystic fibrosis?
- the 3 nt deletion on chromosome 7 decreases CFTR’s stability and increases its folding time
- protein degraded in Golgi apparatus; doesn’t make it to plasma membrane
What is the biochemical reason behind alpha-1-antitrypsin (AAT) deficiency?
- misfolded AAT accumulates in ER of hepatocytes and damages them –> positive PAS granules –> micronodular cirrhosis, fibrosis
- has co-dominant allelic expression: Z and S variants due to point mutations
What is the rate-limiting enzyme in heme synthesis?
ALA synthase: with B6 converts glycine and succinyl-CoA into delta-aminolevulinic acid
-inhibited by lead and heme
Porphyria?
- toxic accumulation of heme synthesis pathway intermediates
- ALA –> neurological sx
- protoporphyrins –> photosensitivity; conjugated structure absorbs light and forms free radicals
- Sx worsened by sunlight, P450 inducing drugs (barbiturates, alcohol)
- Tx: limit sun exposure, P450 inducers, use hemin to inhibit new heme production
Porphyria cutanea tarda?
- uroporphyrinogen decarboxylase deficiency
- autosomal dominant, onset in 4th/5th decade w/ alcohol
- photosensitivity, hyperpigmentation, dark red/brown urine
Acute intermittent porphyria?
- porphobilinogen deaminase
- autosomal dominant, late onset
- no photosensitivity, psych (paranoia, anxiety, depression), abdominal pain, dark red/brown urine (ALA+porphobilinogen)
Consequences of lead poisoning?
- induced deficiency in ALA dehydratase and ferrochelatase; both are Zn2+ dependent enzymes
- increase in ALA w/out increase in PBG
- IQ decreased, microcytic anemia w/ basophilic stippling, abdominal pain, lead lines in bone/teeth X-rays, nephrotoxicity (deposition in proximal renal tubule cells’ nuclei)
