Flashcards in Biochemistry - Part 2 - More important concepts Deck (74)
What enzyme defect causes PKU?
Either defect in phenylalanine hydroxylase (more common) or defect in dihydrobiopterin reductase (regenerates BH4 from BH2).
What is the musty / mousy odor in PKU due to?
Accumulation of abnormal phenylalanine metabolites
Severe intellectual disability, seizures, respiratory failure in a young boy with substantia nigra, locus ceruleus, vagal nucleus dorsalis pallor
A phenylalanine metabolite, along with phenylacetate, which accumulates in PKU and contributes to the brain damage
Path from tyrosine to the TCA cycle
Tyrosine -->homogentisate -(homogentisic acid oxidase)-> maleylacetoacetate -> fumarylacetoacetate -> fumarate -> TCA
What are the branched chain amino acids?
I Love Vermont Maple syrup - Isoleucine, leucine, Valine
What enzyme catalyzes decarboxylation of the alpha-ketoacid derivatives of the branched chain amino acids?
Branched chain ketoacid dehydrogenase
Ptosis, orthostatic hypotension, hypoglycemia, hypothermia
Defect in dopamine hydroxylase
Homogentisic acid oxidase
Catalyzes the degradation of tyrosine
Autosomal recessive disorder of tyrosine degradation caused by deficiency of homogentisic acid oxidase. Accumulation of large amounts of homogentisic acid. Connective tissue hyperpigmentation, degenerative joint disease.
Depressed or absent tyrosinase activity leads to...
tyrosine --> DOPA -(tyrosinase)-> dopaquinone
Missense mutation where one amino acid is replaced with another amino acid with similar biochemical characteristics
Deficiency of alpha-galactosidase A
Accumulation of ceramide trihexoside
Hypohidrosis, acroparesthesia, angiokeratomas... and without enzyme replacement, renal insufficiency and renal failure and death.
Episodic, debilitating, neuropathic pain in the extremities
Punctate, dark red, nonblanching macule and papule that occur between umbilicus and knees
Acute leukemia is associated with which genetic disorders?
Caused by impaired galactose-1-phosphate uridyl transferase (GALT) which converts Galactose 1P to UDP-galactose (transfers UDP from UDP-glucose)
Galactosyl beta-1, 4 glucose
Another name for lactose
Vomiting, lethargy, failure to thrive soon after breastfeeding is begun
Hyperchloremic metabolic acidosis, amino aciduria, impaired liver function.
Irreversible eye and liver damage from galactitol accumulation
Less severe; may cause cataracts?
PRPP synthetase gene increased activation
Leads to increased purine synthesis pathway and degradation --> increased gout risk.
What cells are responsible for the intense inflammatory response seen with gout?
Neutrophils - phagocytosis of urate crystals leads to release of various cytokines and inflammatory mediators that lead to further neutrophil activation and chemotaxis, resulting in a positive feedback loop that amplifies the inflammatory response.
What is the treatment for gout?
NSAIDs are first line because they inhibit prostanoid biosynthesis through COX2 I believe.
Colchicine - decreases tyrosine phosphorylation in response to monosodium urate, resulting in decreased neutrophil activation. Inhibits neutrophil chemotaxis and phagocytosis by preventing microtubule formation.
Growth hormone receptors act through what pathway?
Attach to extracellular domain of growth homrone receptor --> dimerization --> conformation change of JAK --> tyrosine kinase activity --> STAT transcription activity
Vitamin deficiency after 4 years?
How long does Vitamin A last?
6 months - contained in perisinusoidal stellate Ito cells of the liver
How long does folate last?
3-4 months, liver contains half of the body's folate.
Vitamin K - how long does it last?
Lynch syndrome - HNPCC - which genes are mutated?
MutS or MutL
Severe fatigue, splenomegaly (often causing early satiety/abdominal discomfort), hepatomegaly, anemia, bone marrow fibrosis
Primary myelofibrosis - JAK2 mutation
Pruritis, erythromelalgia, splenomegaly, thrombotic complication, erythrocytosis, thrombocytosis
Polycythmia vera - JAK2 mutation
Hemorrhagic and thrombotic symptoms (easy bruising, microangiopathic occlusion, thrombocytosis and megakaryocytic hyperplasia)
Essential thrombocytosis - JAK2 mutation
Constitutional sx (fatigue, wt loss, excessive sweating), splenomegaly, leukocytosis with left shift (myelocytes, metamyelocytes, band forms)
BCR:ABL - CML
JAK2 inhibitor approved for treatment of primary myelofibrosis
Valine --> Phenylalanine at 617 in JAK2
Constitutive tyrosine phosphorylation activity leading to the chronic myeloproliferative disorders
15;17 translocation in acute promyelocytic leukemia
Leads to PML and retinoic acid receptor alpha fusion gene which blocks differentiation of myeloid precursors.
EGF, PDGF, FGF signal through...
MAP Kinase - receptor autophosphorylates and triggers phosphorylation of ras
First step in glycogen degradation
1,4 glycosidic linkage to form glucose-1-phosphate
How do you convert pyruvate to PEP for gluconeogenesis?
pyruvate --> oxaloacetate through pyruvate carboxylase
oxaloacetate --> malate (malate dehydrogenase in mitochondria)
malate --> oxaloacetate (cytosolic malate dehydrogenase)
oxaloacetate --> PEP (phosphoenolpyruvate carboxykinase - PEPCK)
What enzymes differ between glycolysis and gluconeogenesis?
pyruvate -> PEP
fructose 1,6 bisphosphatase (bypasses phosphofructokinase)
glucose-6-phosphatase (bypasses hexokinase)
How do aminoglycosides work?
Impair INITIATION of protein synthesis and inhibit formation of INITIATION complex.
How do tetracyclines work?
Interfere with amino-acyl-tRNA binding to the A site
Acetyl CoA carboxylase
Biotin dependent enzyme in liver and adipose tissue that catalyzes the first committed step in fatty acid synthesis, which occurs in the cytosol.
Where does fatty acid oxidation occur?
Where does fatty acid synthesis occur?
Oxidation - Mitochondria
Synthesis - Cytosol
alpha 2 gamma 2
alpha 2 delta 2
earliest hemoglobin found in the fetus?
Hemoglobin gower, zeta 2 epsilon 2, synthesized in the yolk sac --> hemoglobin portland --> hemoglobin gower 2 --> hemoglobin F at 10-12 weeks
4 gamma proteins (gamma 4).
Found in homozygous alpha thalassemia
High affinity for oxygen and does not release it to the tissues --> tissue hypoxia.
NO comes from which AA?
Arginine ("Argh! NO!")
Urea comes from which AA?
Arginine + aspartate
Heme comes from which AA?
Glycine + succinyl CoA
Creatinine comes from what things?
Glycine + arginine + SAM
GABA comes from which AA?
Glutathione comes from which AA?
Pyrimidines come from which AA?
Glutamate + aspartate
Purines come from which AA?
Glutamate + aspartate + glycine (GAG)
Niacin comes from which AA?
Tryptophan ("toe fan")
Thyroxine comes from which AA?
Melanin comes from which AA?
eNOS - endothelial nitric oxide synthase - synthesizes nitric oxide from what?
Arginine, NADPH, and O2
Which processes occur outside the cell in collagen synthesis?
Terminal propeptides cleaved by N and C-procollagen peptidases.
Collagen molecules spontaneously assemble.
Covalent cross-links formed by lysyl oxidase.
Newly synthesized, unmodified alpha chain (first step in collagen synthesis)
After hydrophobic signal peptide at N terminus is cleaved from the pre-pro-alpha chain (collagen formation)
Triple collagen helix which has had disulfide bond formation, hydroxylation of proline and lysine residues.
Sideroblastic anemia enzyme
d-aminolevulinate synthase, requires B6
Heme in liver versus heme in bone marrow
Liver --> used for cytochrome p450 system
Bone marrow --> used for hemoglobin
Heme negatively feedback inhibits what?
Reduction in heme synthesis leads to increased d-aminolevulinic acid and porphobilinogen which lead to acute abdominal pain and neurologic sx.
What does lead inhibit?
ALA dehydradatase and ferrochelatase
Infants are unable to properly form myelin in the CNS.
Hypotonia and seizures, hepatomegaly, mental retardation, early death within months
Defect in peroxisomal alpha oxidation --> neurological disturbances in response to accumulation of phytanic acid within the body. Strictly avoid chlorophyll in the diet.