week 3

Question 1

Tay Sachs Disease

Answer 1

lysosomal storage disease; buildup of undigested cell products inhibits cell functioning and results in cell death

Question 2

secretary granules

Answer 2

vesicle containing secretary granules found near the plasma membrane; present in cells that use regulated secretion in response to a signal

Question 3

Lack of Electron Transfer Flavoprotein (ETF) or the ETF: CoQ reductase

Answer 3

leads to glutaric acidemia type II; build up of glutaric acid due to amino acids getting degraded for energy; can get severe hypoglycemia and death; severe symptoms under fast fatty acid oxidation symptoms; more mild forms may be treated with riboflavin administration

Question 4

Carnitine deficiency

Answer 4

inability to transfer amino acids into the mitochondria; leads to weakness, fasting hypoglycemia, triglyceride accumulation in muscles and liver; treat by adding carnitine to the diet

Question 5

Primary carnitine deficiency

Answer 5

unable to get carnitine into the cells, treating with carnitine may help; also diet with high amount of short chain fatty acids which can diffuse into mitochondria without transporter; low plasma carnitine levels in the urine because it can’t get in the cells

Question 6

Secondary carnitine deficiency

Answer 6

defect in fatty acid oxidation; all of the carnitine gets used up and gets stuck on acyl group, forming acyl-carnitines, which accumulate, leading to detrimental nervous system functioning; short chain fatty acid diet doesn’t help because still have a fatty acid oxidation defect

Question 7

MCAD deficiency

Answer 7

single AA change from K to E (positive to negative) leads to unstable protein; hypoglycemia when fasting, can’t fully do fatty acid oxidation because medium chain dicarboxylic acids build up along with hexanoylglycine; don’t have enough energy for gluconeogenesis; lack of ketone bodies because lack of acetyl CoA

Question 8

Zellweger syndrome

Answer 8

lack of peroxisomes, accumulation of very long chain fatty acids and branched fatty acids, which has negative effects on nervous system

Question 9

Refsum disease

Answer 9

loss of alpha oxidation (phytanic acid oxidase) which leads to phytanic acid accumulation (branched chain), which is incorporated into myelin sheath, causing neural dysfunction

Question 10

Adrenoleukodystrophy

Answer 10

mutation in transport protein on peroxisome membrane, leads to accumulation of very long chain fatty acids which affect adrenal glands and nervous system; X linked disorder; treatment with Lorenzo’s oil, early treatment can slow disease progression

Question 11

Acyl-CoA oxidase deficiency

Answer 11

enzyme that does first step of oxidation to oxidize the fatty acid and produce hydrogen peroxide; 2 types- ACOX1- straight chain enzyme deficiency- neonatal hypotonia, seizures, death; ACOX2- branched chain enzyme- severe neurological disfunction, similar to Refsum

Question 12

Jamaican vomiting sickness

Answer 12

eating unripe ackee fruit produces hypoglycin toxin which is metabolized into compound which tightly binds FAD, interferes with short and medium chain acyl CoA DH; inhibits gluconeogenesis by the reduction of NADH and acetyl CoA levels; severe hypoglycemia and elevated fatty acids in blood, along with dicarboxylic acids; can be fatal

Question 13

G6PDH deficiency

Answer 13

leads to lack of NADPH, detrimental to RBCs when they undergo oxidative stress, oxidized glutathione can’t be converted to the protective, reduced form which neutralizes the oxidative stress; damage to RBC membrane leads to cell lysis and thus anemia; hidden disorder unless exposed to oxid. stress (fava beans, anti-malarial drugs); X linked recessive, gives selective resistance to malaria- growth of parasite in the RBCs leads to membrane damage and cell lysis (b/c no NADPH), cells invected then are lysed and removed from circulation- more mild disease

Question 14

Sickle cell resistance to malaria

Answer 14

HbS/HbA cells (carrier) have different miRNA subset produced- become incorporated into parasite mRNA disrupting maturation of the parasite; placing a certain 3 miRNA molecules into a normal (non-carrier) person will give a resistance to malaria

Question 15

Rapoport Leubering shunt

Answer 15

1,3 BPG from glycolysis can be used to generate 2,3 BPG in RBCs which then stabilizes the T state (deoxy)

Question 16

Radical chain terminators

Answer 16

anti-oxidants, reduce damage from radicals; vitamin A (beta carotene), vitamin E, and vitamin C

Question 17

Lou Gehrig’s disease (ALS)

Answer 17

mutated superoxide dismutase enzyme (converts superoxide to hydrogen peroxide in mito) which leads to oxidative damage

Question 18

Burkitt’s lymphoma

Answer 18

chromosomal translocation places myc gene under control of highly active promoter- leads to constant expression of myc and uncontrolled cell division in lymphocytes; myc is converted from proto-oncogene to oncogene; myc results in phosphorylation of G1 CDK which activates it, and CDK phosphorylates and inactivates Rb to release the E2F TF- S phase transcription of cyclins needed for the active cyclin-CDK complex

Question 19

Prader willi syndrome

Answer 19

deletion on paternal chromosome 15, corresponding genes are imprinted (off) on maternal chromosome- there are no active genes; short stature, mental delay, decreased muscle tone, unregulated appetite- obesity; can only be passed down by males because females will reset the genes during gametogenesis to be imprinted

Question 20

Angelman syndrome

Answer 20

deletion on maternal chromosome 15, corresponding paternal genes are imprinted (off), meaning no genes are expressed; normal development during first year and then delayed development microcephaly, seizures, language deficit, motor problems; can only be passed down by females because males will reset the methylation pattern and the mutated genes are imprinted/switched off

Question 21

Sickle cell disease

Answer 21

mutation in the beta chain from glutamate to valine creates a hydrophobic patch on the surface of the deoxy Hb molecule, causing aggregation with other deoxy molecules; these aggregates distorts the shape of the RBC into a sickle, which clump together in blood vessels, blocking blood flow

Question 22

Ehlers Danlos

Answer 22

defects in structural collagen genes and enzymes involved in post TL mod (lysyl hydroxylase, procollagen N peptidase); very mobile joints and skin hyperextensivity, tissue fragility

Question 23

Osteogenesis imperfecta

Answer 23

family of mutations in structural collagen genes; usually involves mutation of glycine to another residue, which disrupts the triple helix structure, making it unstable and resulting in very fragile bones and teeth

Question 24

Williams Syndrome

Answer 24

mutation in elastin genes results in narrowing or aorta or arteries (elastin is dominant protein in arteries); may lead to supravalvular aortic stenosis, hypertension, hypercalcemia, small, widely spaced teeth

Question 25

Alpha-1-antitrypsin deficiency

Answer 25

alpha 1 antitrypsin coats lungs to protect from neutrophil elastase enzymes; deficiency leaves lungs vulnerable to damage and can lead to liver damage- incorrectly processed proteins accumulate in the liver; membrane in lungs breaks down