Biochem 3 Flashcards
In what conditions does HbS tend to sickle and aggregate?
> Low O2 levels, inc. acidity, low blood volume (dehydration) – liver and spleen prone to low O2 or acidity; brain and muscles have higher O2 demands.
HbS tend to agregate when in a deoxygenated state when membrane flexibility is decreased.
What organs are affected by Niemann-Pick disease? How does this disease present?
N-P dse is due to sphingomyelinase deficiency. Foam cells lead to hepatosplenomegaly and affect the CNS (hypotonia, neurodegeneration). Infants fail to attain new skills and lose old ones. Retinal accumulation leads to cherry-red macular spot.
What two enzymes may be involved in Organic acidemia? The catabolism of which amino acids are affected?
Organic acidemia may involve propionic acidemia and methylmalonic acidemia, w/c are caused by deficient propionyl-CoA carboxylase and methylmalonyl-CoA mutase, respectively. These enzymes are involved in the catabolism of Valine, Isoleucine, Methionine, and Threonine.
How does organic acidemia (proprionic acid, methylmalonic acid) present?
Accumulated proprionate (and methylmalonate) leads to severe metabolic acidosis. The organic acids also directly inhibit gluconeogenesis and the urea cycle, leading to hypoglycemia and hyperammonemia. Ketone prodn furthers the anion gap w/ inc. FFA metab. Infants show lethargy, poor feeding, vomiting, and hypotonia.
What enzyme is deficient in Phenylketonuria, and what AA becomes essential in these patients?
> Phenylalanine hydroxylase deficiency.
Tyrosine becomes essential in diet. Patients present w/ fair complexion or partial albinism due to lack of melanin forming from tyrosine. Accumulated Phe can cause intellectual disability, seizures, and “musty” odor in patients.
What enzyme is deficient in Alkaptonuria? How does this disease present?
> Homogentisate dioxygenase deficiency
Homogentisate accumulation gives black color to urine, black color to collagen (ochronosis of ears, nose, cheeks), and Ochronotic arthropathy.
What specific hormones bind to intracellular receptors (transcription factors)?
Only lipid-soluble hormones like Thyroid hormone, estrogen, aldosterone, and cortisol can bind to intracellular receptors and affection DNA transcription.
What are zinc-finger motifs?
DNA-binding domains made from zinc linked w/ cysteine and histidine residues. Transcription factors use zinc-finger motifs to recognize specific genes and alter their activity.
Only lipid-soluble hormones can bind to intracellular receptors that act as transcription factors.
What condition are patients w/ Homocystinuria at risk of developing?
Homocysteine is prothrombotic, so patients are at risk of developing Acute coronary syndrome and atherosclerosis. Thus, Homocysteinuria is a condition of hypercoagulability and thromboembolism, also involving ectopia lentis, hypermethionemia, and intellectual disability.
What process during Elastin assembly gives elastin its rubber-like qualities?
After tropoelastin interacts w/ microfibril scaffolding in the extracellular space, lysyl oxidase deaminates lysine residues to allow for cross-linking w/ neighboring peptides. These crosslinks make elastin more rubbery.
What AA is particularly neurotoxic for patients w/ Maple syrup urine disease?
Branched-chain alpha-ketoacid DHG deficiency leads to elevated leucine, isoleucine, and valine. Inc. leucine levels is neurotoxic, so infants present w/ progressive neuro ssx. There’s also poor feeding and hypertonia. Patients have lifelong risk for neurotoxicity during intercurrent illnesses and fasting.
What specific autoantibody marker is seen in Rheumatoid arthritis?
Anti-cyclic citrullinated peptides antibodies.
*Tissue inflammation causes arginine residues in proteins (vimentin) to be converted into citrulline. These altered proteins serve as antigens that generate an immune response.
In a well-fed state, how is beta-oxidation inhibited in order to prevent the breakdown of newly synthesized fatty acids?
High ATP levels in hepatocytes inhibit isocitrate DHG, leading to citrate build-up, w/c is cleaved in the cytosol into acetyl-CoA. Acetyl-Coa upregulates acetyl-CoA carboxylase and is converted into malonyl-CoA for FA synthesis. Malonyl-CoA inhibits carnitine acyltransferase of B-oxidation.
What is the pathogenesis of Pompe disease?
Glycogen is mostly degraded in the cytoplasm, but some is engulfed by lysosomes, esp. in liver and myocytes (cardiac, skeletal muscle). With acid maltase deficiency, there is accumulation of fat in these lysosomes, and their ballooning interferes w/ contractility. Infants have cardiomegaly, hypotonia, hepatomegaly, macroglossia.
