Lecture Twenty-Seven - Triacylgleycrols Phospholipid & Sphingolipid Metabolism

Glycerolipids contain ____ while sphingolipids contain _____

Glycerol; sphingosine

Ether glycerophospholipids differ from other glycerophospholipids in that the alkyl or alkenyl chain is joined to carbon I of the glycerol moiety by an ether rather than what type of bond?

Ester

What serve as an energy source for metabolic fatty acids?

Triglycerides (TG)

What are particularly important in forming the myelin sheath surrounding nerves in thecentral nervous system?

Sphingolipids

Since adipose tissue does not have what enzyme, it must derive glycerol-3-phosphate entirely from glycolysis?

Glycerol kinase

In liver, the source of glycerol-3-P is produced from the phorsphorylation or dephosphorylation of glycerol by what enzyme mainly?

Phosphorylation of glycerol by glycerol kinase

What is another way in which the source of glycerol-3-P is produced from in the liver that involves reduction?

Reduction of dihydroxyacetone phosphate (DHAP)

In liver and adipose tissue, triacylglycerols (TG) are produced by a pathway containing a what type of intermediate?

Phosphatidic acid

Regarding the incorporation of TG into VLDL, the TG produced in the ________ ___________ __________ of the liver, is packagedwith cholesterol, phospholipids, and proteins (ApoB-100) synthesized in the ________ ___________ __________ and ______ _____________ and is secreted into the blood by the liver.

Smooth endoplasmic reticulum; Rough endoplasmic reticulum; Golgi complex

What enzyme do adipose cells synthesize? Once this enzyme is synthesized, it is secreted into the capillaries of adipose tissue when the insulin/glucagon ratio is high (fed state).

LPL

What enzyme digests the TG in VLDL & chylomicrons to FA which enter adipose cells forming FACoA that reacts with glycerol-3P to form TG that is added to TG formed from glucose?

LPL

What are TGs from food are packaged into?

Chylomicrons

What are synthetic TGs are packaged into?

VLDL

When insulin is low & glucagon is elevated, CAMP increases & activates protein kinase A, which does what to HSL and in turn initiates what pathway?

Phosphorylates HSL; Initiates lipolysis

What is the name of the type of phospholipid that has a glycerol backbone, 2 fatty acids, with a head group attached through a phosphate?

Glycerophospholipids

In the initial step of synthesizing glycerophospholipids, glycerol-3-p reacts with fatty acyl CoA to form what?

Phosphatidic acid

How many different mechanisms are used to add a hydrophilic head group after phosphatidic acid is formed in the synthesis of glycerophopholipids?

Two different mechanisms

In both of the two different mechanisms that are used to add a hydrophilic head group after phosphatidic acid is formed in the synthesis of glycerophopholipids, what is used to drive the reaction?

Cytidine triphosphate (CTP)

What are the three interconversions of phospholipids involved in the synthesis of glycerophospholipids?

Phosphatidyicholine (PC), Phosphatidylethanolamine (PE) and Phosphatidylserine(PS)

What are the four enzymes involved in the degradation of glycerophospholipids?

Phospholipase A1, phospholipase A2, phospholipase C and phospholipase D

Which of the four enzymes involved in the degradation of glycerophospholipids removes the fatty acyl group on carbon 1 of the glycerol moiety?

Phospholipase A1

Phospolipases are found where in the cell?

Lysosomes

Which of the four enzymes involved in the degradation of glycerophospholipids removes the fatty acid on carbon 2?

Phospholipase A2

Which of the four enzymes involved in the degradation of glycerophospholipids cleaves the bond joining carbon 3 of the glycerol moiety to phosphate?

Phospholipase C

Which of the four enzymes involved in the degradation of glycerophospholipids cleaves the bond between the phosphate and the head group?

Phospholipase D

Do degradation products of Glycerophospholipids play important biological roles in a variety of cellular functions?

Yes

What is made by type II epithelial cells lining the inside of the terminal air sacs (alveoli) of the lung preventing collapse?

Lung surfactant

What is the name of the syndrome that occurs in some newborn infants due to a problem in lung surfactant production or secretion?

Infant respiratory distress syndrome (IRDS)

Diagnosis of surfactant levels in utero is made by obtaining a sample of what fluid?

Amniotic fluid

Is a high or low phophatidyl choline (PC)/sphingomyelin ratio indicative of deficiency in lung surfactant and is predictive of IRDS in the newborn?

Low ratio

What is the type of phospholipids that have an ether bond in the glycerol backbone, 1 fatty acid, and a phosphate attached to the head group?

Ether glycerolipids

What glycerolipid type is synthesized from the glycolytic intermediate dihydroxyacetone phosphate (DHAP)?

Ether glycerolipid

In the synthesis of an ether glycerophospholipid, what does the formation of a double bond between C1 & C2 of the alkyl group produce?

Plasmalogen

What type of plasmalogen in the synthesis of an ether glycerophospholipid is found in myelin?

Ethanolamine plasmalogen

What factor is derived from ether glycerophospholipid with an acetyl group at C2 of the glycerol moiety and a saturated alkyl group on C1?

Platelet activating factor (PAF)

What group of sphingolipids has a sphingosine backbone with one fatty acid and a head group attached via phosphate?

Sphingophospholipids

What group of sphingolipids has a sphingosine backbone with one fatty acid and a carbohydrate?

Glycolipids

What are the four functions are sphingolipids?

1. Components of the plasma membranes.2. Provide receptors for pathogenic bacteria and bacterial toxins 3. Serve as antigen determinants of the ABO blood groups.4. Serve in intercellular communication

What are the two stages of the biosynthesis of Sphingolipids?

1) Formation of Ceramide in the smooth ER2) Attachment of different head groups to Ceramide (in the Golgi Complex)

What two things are involved in the formation of the Ceramide in the smooth ER?

Dihydrososphingosine and 3-ketosphinganin

Where are sphingolipids degraded in the cell?

Lysosomes

What are the four specific enzymes that help sphingolipid degradation in the lysosomes?

Exoglycosidases, sphingomyelinase, arylsulfatase A, and ceramidase

Which one of the four specific enzymes that help sphingolipid degradation in the lysosomes catalyze hydrolysis of specific carbohydrate head groups sequentially from outside in sequentially toward?

Exoglycosidases

Which one of the four specific enzymes that help sphingolipid degradation in the lysosomes cleaves the phospho-choline group?

Sphingomyelinase

Which one of the four specific enzymes that help sphingolipid degradation in the lysosomes is a sulfatidase?

Arylsulfatase A

Which one of the four specific enzymes that help sphingolipid degradation in the lysosomes cleaves between acyl groups and sphingosine?

Ceramidase

What is the term for inherited diseases that are due to an inherited mutation that results in a missing or defective enzyme that plays a role in the degradation of sphingolipids? Characterized by pathologic accumulation of particular sphingolipids in cells of affected individuals

Sphingolipidoses

Which disease is due to a spingolipidoses where there is a lack in the enzyme hexosaminidase A? Make spingolipids can't be broken down

Tay-Sachs disease

Which disease is due to a spingolipidoses where there is a lack in the enzyme b-glucosidase? Make spingolipids can't be broken down

Gaucher's disease

Which disease is due to a spingolipidoses where there is a lack in the enzyme sphingomyelinase? Make spingolipids can't be broken down

Niemann-Pick disease

Which disease is due to a spingolipidoses where there is a lack in the enzyme ceraminidase? Make spingolipids can't be broken down

Farber's disease