Metabolism Of Complex Lipids

Question 1

Phospholipid structure

Answer 1

. Fatty acyl residues sterilized to glycerol

. Hydrophilic head group

Question 2

Glycerophospholipid

Answer 2

. Based on phosphatidylcholine acid
. Most common phospholipids
. Esterification of 1 of several cellular alcohols to phosphate group
.

Question 3

Phophatidic acid

Answer 3

Intermediate formed during TAG biosynthesis

Question 4

Glycerophospholipid biosynthesis

Answer 4

. Most cells in body
. DAG or alcohol must be available in CDP-activated form
. Choline and ethanolamine from diet or turnover of existing phospholipids
. Phosphatidylcholine and CO2 synthesized in liver from phosphatidyl serine

Question 5

Remodeling and degradation of glycerophospholipid

Answer 5

. Phospholipase A1 and A2 and acyltransferases remove or add fatty acyl residues of glycerophospholipids to generate phospholipids w/ specific acyl composition
. phospholipase A2 causes release of arachidonic acid from membrane phospholipids
. Membrane-bound PLC hydrolyzes PIP2 to release DAG and IP3 as secondary messengers

Question 6

Sphingomyelin

Answer 6

. Basic structural unit of sphingolipids
. Synthesized from sphingosine and phosphatidylcholine by sphingomyelin synthase
. Structurally similar to choline-containing glycerophospholipid
. Ceramide + phosphorylcholine -> sphingomyelin +DAG

Question 7

Formation of ceramide

Answer 7

. Serine + Palmitoyl CoA -> sphinganine -> ceramide through acyl CoA

Question 8

Fatty acids most commonly used to acylate sphinganine during conversion to ceramide?

Answer 8

. Palmitic
. Stearin
. Lignoceric
. Nervonic

Question 9

Highest concentration of sphingomyelin is in ___

Answer 9

CNS

Question 10

Phosphatidyl choline in surfactant

Answer 10

. Major constituent of surfactant (90% lipids 10% proteins)
. Modified structure that contains 2 Palmitoyl residues (DPPC)
. Prevents complete collapse of lung alveoli (atelectasis) during expiration
. Effort to reinflate during inspiration dec. making gas exchange more efficient

Question 11

Besides PC, what other lipid is major in surfactant

Answer 11

Phosphatidyl glycerol

Question 12

Surfactant in fetal development

Answer 12

. Composition changes as lung matures
. Before 32 weeks, lecithin:sphingomyelin ratio is <1 (birth at this stage high risk for respiratory distress)
. After the L:S ratio inc. until it reaches 2.0 at 35 weeks

Question 13

Tests of fetal lung maturity

Answer 13

. Amniotic fluid content of phosphatidyl glycerol (PG)
. Surfactant: albumin ratio
. Lamellae body count
. Everything inc. w/ lung maturity

Question 14

Respiratory distress syndrome

Answer 14

. Most commonly in premature babies
. Can occur in adults
. Surfactant-secreting lung cells are destroyed

Question 15

Glycoliipids

Answer 15

. Sugar-containing derivatives of ceramide
. Highest conc. In nerve tissues where they are important component of cell membrane
. Important in intercellular communication
. Some antigenic
. Others receptors for bacterial toxins

Question 16

ABO blood antigens

Answer 16

. On chromosome 9 encoding glycosyltransferase enzyme that transfers specific (or no) carbs to O antigen substance (H substance)
. Different terminal carb residues on membrane lipids or secreted proteins form basis of ABO system

Question 17

Blood group A

Answer 17

Glycosyltransferase specific for N-acetylgalactosamine

Question 18

Blood group B

Answer 18

. Glycotransferase specific for galactose

Question 19

Blood group O

Answer 19

. Nonfunctional enzyme

. H antigen not glycosylated

Question 20

Blood group AB

Answer 20

. Both A and B alleles expressed (codominant)

Question 21

Niemann-pick types A and B

Answer 21

. Enzyme issue: sphingomyelinase (sphingomyelin -> ceramide)
. Sphingomyelin accumulates
. Symptoms: hepatosplenomegaly, mental retardation (type a)

Question 22

Fabry disease

Answer 22

. Enzyme issue: alpha-galactosidase
. Lipid accumulation: Gal-Gal-Glu-Cer
. Symptoms: skin rash, kidney and heart failure

Question 23

Gaucher type 1 disease

Answer 23

. Most common
. Enzyme issue: beta-glucosidase (glucocerebroside -> ceramide)
. Glucosylceramide accumulates w/in lysosomes of macrophages in reticuloendothelial system
. Symptoms: hepatosplenomegaly, osteoporosis of long bones, anemia, thrombocytopenia, growth retardation
. High prevalence in Ashkenazi Jews
. Mutation of GBA gene w/ autosomal recessive inheritance
. Neurological effects only seen in types 2 and 3

Question 24

Tay-Sachs disease

Answer 24

. Enzyme issue: Beta-hexosaminidase A (GM2 ganglioside -> GM3 ganglioside)
. Lipid accumulating: GM2 ganglioside
. Symptoms: mental retardation, muscular weakness, cherry red macula, blindness

Question 25

Pharmacological treatment for Gaucher and Fabry diseases

Answer 25

. Cerezyme
. Fabrazyme
. Enzyme replacement therapy

Question 26

.link btw GBA and Parkinson’s

Answer 26

. Mutation in GBA causing type 1 gaucher’s causes inc. risk for Parkinson’s
. Risk Occurs in patients and in heterozygotic carriers
. Protein misfolding contributing to lysosomal dysfunction, not lipid accumulation assoc. is more important w/ disease