Flashcards in Biochemistry Deck (255)
What is pleiotropy?
One gene causing multiple phenotypic effects
Locus vs. allelic heterogeneity?
Locus heterogeneity means that the same phenotype occurs with mutations at different loci. Whereas allelic heterogeneity is the same phenotype occurs with mutations at the same loci.
Presence of both nl and mut mtDNA. Examples of mitochondrial syndromes are Leber hereditary optic neuropathy, myoclonic epilepsy w/ ragged-red fibers, mitochondrial encephalomyopathy w/ lactic acidosis and stroke-like episodes (MELAS)
2 copies of a chromosome from 1 parent; heterodisomy (meiosis I error); isodisomy (meiosis II or later error). Can cause what appears to be imprinting-related disease (Prader-Willi or angelman)
No mutations, no natural selection, no migration, random mating
What is imprinting?
At some loci, only one allele is active while the other is inactivated/imprinted by methylation.
Prader-Willi - normally maternal imprinting; Disease occurs if PATERNAL gene problem;
AngelMan - nl paternal imprinting; disease occurs if MATERNAL gene problem
Example of X-linked dominant disease?
What are the two parts of the pentose phosphate pathway? (And what is its function)
Irreversible oxidative pathway (G-6P ->-> Ribulose-5-phosphate); creates 2 NADPH
Reversible nonoxidative pathway (Ribulose-5-P Fructose-6-P --> Glycolysis)
Function = generate NADPH for synthetic pathways and detox + produce Ribose-5P for nucleotide synthesis
Rate limiting step of pentose phosphate pathway?
1st step done by glucose-6-phosphate dehydrogenase
Deficiency in rate-limiting step of pentose phosphate pathway. Decreased production of NADPH. RBC's in particular are vulnerable to oxidative stress (e.g. fava beans, tylenol, primaquine, sulfa, dapsone, DKA). Heinz bodies (denatured hgb). Bite cells from phagocytic removal of Heinz.
Sickle cell anemia point mutation?
6th codon of Beta-globin gene: glutamic acid -> valine
What vitamin does the WHO recommend administering to those with measles?
Alpha-ketoglutarate dehydrogenase complex requires what coenzymes?
Thiamine, lipoic acid, CoA, FAD, NAD+
Presentation of phenylketonuria
Scandinavian descent; Within a year - mental retardation, sz, hyperactivity, gait, postural muscle control, dec. pigmentation, "mousy" odor. There exists maternal PKU where baby is affected.
Etio of phenylketonuria
Enzyme phenylalanine hydroxylase (phenylalanine req. BH4-> tyrosine); Tyrosine req. BH4 -> DOPA -> melanine and catecholamines; Tyrosine -> Fumarate -> TCA
Dihydrobuipterin reductase (BH2->BH4) deficiency
What are the substrates for gluconeogenesis?
Pyruvate from lactate, glycerol, and glycogenic amino acids
How does sucrose/sorbitol get into glycolysis?
Sucrose -> fructose -(fructokinase)> fructose 1-P -(Aldolase B)> Glyceraldehyde -(triokinase)> Glyceraldehyde 3-P
Hereditary fructose intolerance?
Aldolase B deficiency - vomiting and hypoglycemia (b/c accumulation of fructose-1-phosphate and depletion of Pi) about 20-30 minutes after fructose intake
Fructokinase deficiency -> secretion into urine of fructose; a benign AR disorder
Methionine to SAM (ATP). SAM to Homocysteine. Homocysteine to Methionine (Homocysteine methyltransferase,B12). Homocysteine to Cystathionine to Cysteine (Cystathionine synthase,B6,serine)
Role of leptin
Decreases NPY (appetite stimulant) and stimulates POMC and alpha-MSH to inhibit food intake
How is isoniazid metabolized?
Acetylation to N-acetyl-isoniazid in hepatic microsomal system --> urine. "Slow acetylators" exist -> increased risk of side effects
How do thiazolidinediones work?
Activate PPAR-gamma, nuclear receptor, that increases transcription of Adiponectin, FA transport protein, insulin receptor substrate, glut-4
PKD1 on chromosome 16 (85%); 16 letters in PK
Familial adenomatous polyposis gene v. HNPCC (lynch)
FAP is APC gene on chr 5 (polyp =5); HNPCC = mismatch repair genes (MSH2, MLH1)
Familial hypercholesterolemia defect?
Defective/absent LDL receptor; tendon xanthomas (Achilles)
Hereditary spherocytosis defect?
Spectrin or ankyrin -> hemolytic anemia (inc. MCHC); tx = splenectomy
(CAG)n on chromosome 4; (The CAG is hunting 4 cylons.)
Marfan syndrome defect