Membrane Lipids & Bile Acid Metabolism

Question 1

Major Phospholipids & Characteristics

Answer 1

Phosphatidylcholine (lecithin)

Phosphatidylserine

Phosphatidylethanolamine

Phsophatidylinositol

• all contain FA
• phosphoglycerides & sphingolipids syn in all body tissues on ER except erythrocytes
• Enzymes present in cytoplasm or associated w/ ER mem

Question 2

Phsopholipid Structure

Answer 2

Question 3

Phospholipid Syn

Answer 3

Question 4

Phosphatidylcholine Syn from phosphatidylserine

Answer 4

SAM very important methyl group donor

Question 5

Salvage Pathway

Answer 5

Phosphatidylcholine can by synthesized from dietary choline when available.

If not available, PC can be made from glycolytic producs but isn’t suffiicient to prevent choline def

Question 6

Cardiolipin

Answer 6

found in inner mitoch mem where maintains certain resp complexes on ETC

Only human glycerophospholipid that is antigenic

Can be recognized by Y against trepanoma pallidum (syphalis)

Autoimmune disease

Question 7

Dipalmitoylphosphatidylcholine

Answer 7

Major part of lung surfactant

Made & secreted by granular pneumocytes

Lung surfatant lines alveoli

Decreases surface T of fluid layer reducing P needed to reinflat alveoli preventing collapse

Question 8

Respiratory Distress Syndrome

Answer 8

Prevalent in premature infants

Due to def in syn of lung surfactant

Major constituents of surfactant are dipalmitoylphosphatidylcholine, phosphatidylglycerol, apoproteins (Sp A, B, C) & cholesterol

Measure: DPPC/S ratio 2:1 maturity

Question 9

Platelet Activating Factor

Answer 9

present @ low [] but EXTREMELY potent!

Hormone released from phagocytic cells binds to surface proteins.

Causes platelets to aggregate & degranulate. It binds to surface R resulting in thrombotic & inflammatory events & anaphylactic rxns.

Causes neutrophils & alveoli macrophages to produce superoxide radicals

Question 10

Plasmalogen (ethanolamine)

Answer 10

Phosphatidalethanolamine (in nerves)

Phosphatidalocholine (abundant in heart m.)

Found w/in peroxisomes

Question 11

Plasmalogens 2

Answer 11

Plasmalogen def plays important role in Alzheimer’s disease pathogenesis, particularly in white matter, & suggested that altered plasmalogen content contributes to neurodegen & synapse loss.

Syn of plasmalogens occur w/in peroxisomes & in patients w/ Zellweger syndrome- little to no syn which results in death at an early age if it’s severe

F not well known. Resistance to phsopholipases?

Question 12

Phospholipases

Answer 12

Degradation & remodeling of phospholipids

Present in cell mem & lysosomes of all tissues & pancreatic secretions

*not in humans

Question 13

Phospholipase actions

Answer 13

Question 14

Phospholipase 2

Answer 14

Question 15

Glycosphingolipids

Answer 15

Intracell communication

Found on outer leaflet of PM where they interact w/ extracell environment

Play a role in regulation of cell interactions, growth & dev

Act as antigenic determinants of ABO blood group & also source of various embryonic antigesns important in particular stages of fetal dev

Essential components of all cell mem but found in nerve tissue

Some are antigenic

Question 16

Tay Sachs

Answer 16

auto recessive

Hexoaminidase A def

GM2 ganglioside in nerve cells accumulates

Mental retardation, blindness, m. weakness, seizures, cherry-red macula, early mortality

infantile/juvenile/adult

Question 17

Guacher disease

Answer 17

auto recessive

Glucoceribrosidase def

Glucocerebroside accum in spleen, liver, lungs, bone marrow & brain

Hepatosplenomegaly

mental retardation in type 2 & 3

skeletal disorder in type 1

Use enz replacement therapy

Question 18

Fabry

Answer 18

x linked

a galactosidase A def

Globosides accum in eyes, kidneys, ANS & cardiovascular sys

Kidney failure, heart failure or stroke, reddish purple skin rashes, burning sensation in hands

use enz replacement

Question 19

Niemann Pick disease

Answer 19

Auto recessive

Sphingomyelinase def

Sphingomyelin accum in spleen, liver, lungs, bone marrow & brain

Type A- jaundice, hepatomegaly, profound brain damage (infantile)

Type B- large liver & spleen (teens)

Type C/D- moderate enlargement of spleen & liver, extensive brain damage (adult)

Bone marrow transplant

Question 20

Krabbes disease

Answer 20

Auto rec

B galactosidase def

Galactocerebroside accum. Globids cells, breakdown myelin in nerve, destruction of brain cells

Mental, motor deterioration, irritability, fever, seizures, vomiting, feeding difficulty, m. weakness, deafness, blindness

Question 21

Sandhoff Disease

Answer 21

Auto Rec

Hexosaminidase A & B def

GM2 & globosides accum in brain & other organs

Severe form of Tay Sachs, motor weakness, early blindness, macrocephaly, cherry red spot in eye, seizures infantile

Question 22

Metachromatic leukodystrophy MLD

Answer 22

auto recessive

Arylsulfatase A def

Sulfatides accum in nervous sys, liver, kidney

Difficulty walking, m. wasting & weakenss, blindess, convulstions, impaired swallowing, paralysis, dementia (infantile) dementia, (juvenile) psychiatric disorder (adult)

Question 23

Farber Disease

Answer 23

auto recessive

Ceraminidase def

Ceramid accum in joints, CNS, liver, heart, kidney

Impaired motor & mental ability, difficulty swallowing, arthritis, swollen LN & joints, horesness (infantile)

Question 24

Sphingolipidoses

Answer 24

1. measure enz activity in cultured periph leukocytes or macrophages
2. histological exam of tissues: tay sach’s shell like inclusions; Gaucher inclusions more like wrinkeled paper
3. DNA analysis (southern blotting)
4. prenatal diagnosis using amniocytes or chorionic villi

Question 25

Cholesterol

Answer 25

Free cholesterol is esterified in mucosal cells w/ FA. Packaged into chylomicrons for liver transport.

All body cholesterol stored in cells as lipid droplets in esterified form.

Question 26

Cholesterol Metabolism

Answer 26

All cholesterol circulating in blood contained in lipoproteins; LDL

Cholesterol necessary for syn of steroid hormones & bile acids

High levels of plasma cholesterol strongly associated w/ atherosclerosis & CHD

Question 27

DIetary Cholesterol

Answer 27

Rate of syn of cholesterol regulated by feedback I of HMG-CoA reductase by excess cholesterol.

If large amts of dietray cholesterol entering the liver then rate of syn is inhibited.

Excess cholesterol excreted as bile acids which result in 7 a hydroxylase actiavtion

Cholesterol doesn’t get absorbed in intestine.

Question 28

Bile Acid Syn

Answer 28

Question 29

Secondary Bile Acids

Answer 29

in lower parts of small intestine

modified by ba enz

deoxychoic acid & lithocholic acid

Question 30

7 a hydroxylase

Answer 30

controllled by - feeback of bile acids

requires thyroid hormones & vit C for activation

(patients w/ hypothyroidism get hypercholesteronemia)

Question 31

Bile Acid Syn Clinically

Answer 31

Syn & excretion in feces only mech to rid of excess cholestrol

BA & phospholipids solubilize cholesterol in bile preventing precipitation of cholestrol in gallbladder.

facilitate digestion of diet TAG by acting as emulsyfiers that render fats accessible to pancreatic lipases

Facilitate intestinal absorption of fat soluble vitamins

Question 32

Bile duct obstruction

Answer 32

Pale stools= lack of pigments, steatorrhea

itching= bile in blood stream

jaundice= conjugated billirubin (causes brown color for poop)