Hardman - Acylglycerols and Sphingolipids Flashcards
Tay Sachs
Hexosaminidase A
Fabry’s Disease
alpha-galactosidase
Methachromatic Leukodystrophy
arylsulfatase A
Krabbe’s Disease
Beta-galactosidase
Gaucher’s Disease
Beta-glucosidase
Niemann-Pick
sphingomyelinase
Farber’s Disease
Ceramidase
What is the common intermediate in synthesis of TAGs and phospholipids
Phosphatidate
Steps in synthesis of phosphatidate
How many fatty acids does this have?
Which on would likely be saturated?
- Dihydroxyacetone + Glycerol = L-Glycerol 3-Phosphate
- Add 1-FA = Lysophosphatidate
- Add 1-FA = Phosphatidate
- 2 Fatty Acids
- Usually Carbon #2
From phosphatidate (2-fatty acids + glycerol + phosphate), how do you add a third Fatty Acid?
- Remove Phosphate (phosphatase)
- Add ACTIVATED fatty acid
- CoA activates
What enzyme in the blood is required to release glycerol from the TAG in blood?
Lipoprotein Lipase
What are the steps of glyceroneogenesis?
Pyruvate
(Pyruvate Carboxylase)
OAA
(Pep CarboxyKinase)
PEP
I
Dihydroxyacetone Phosphate
(Glycerol 3-phosphate dehydrogenase)
Glycerol 3-phosphate
What does elevated FFA in blood result in?
- Increase insulin resistance
- Muscle can’t handle glucose directly
What is result of glucocorticoids (stress hormones) on the TAG cycle?
INHIBITS: PEPCK in Adipose Tissue–shuts down glyceroneogenesis
ACTIVATES: PEPCK in Liver Tissue–increases glyceroneogenesis
How does Thiazolidinediones act on tissues?
What is this a common treatment for?
Activates: PEPCK in Adipose Tissues–spins up glyceroneogenesis
Type II Diabetes
- Increase STORAGE of Fatty Acids in Adipose Tissue
- Reduce Fatty Acid circulation
- Tissues become more dependent on Glucose
What is the effect of insulin on Carb/Protein metabolism, and Acetyl-CoA?
Activates Acetyl-CoA production
Activates Fatty Acid synthesis from Acetyl-CoA
You just ate, insulin high. You want to product Acetyl-CoA to make energy, and use any leftover to begin storage
What are four components of phospholipids?
- Fatty Acid
- Glcyerol or Sphingosine Backbone
- Phosphate Group
- An “Alcohol” (choline, etc)
What is the order for synthesis of phospholipids?
- Synthesis of backbone
- Attach Fatty Acids
- Add hydrophilic head group through phosphodiester bond (phosphate)
- Alter head group with “alcohol”
What must be done before addition of final “alcohol” group to phospholipid?
Either phosphatidate or alcohol must be activated with CDP
What are the three most common “alcohol” moieties?
Choline
Glycerol
Inositol
Cardiolipin
Diphosphatidul Glycerol
Basically two phospholipids with a shared glycerol “alcohol” in the middle
How is phosphatidylcholine synthesized?
Methylation of phosphatidylethanolamine
How is phosphatidylserine synthesized?
Base Exchange reaction with phos-choline or phos-ethanolamine
What is the structure of sphingosine?
Single fatty acid on carbon 3 w/ 2x “open” carbons
- One amine group on open carbon 2
- One alcohol group on open carbon 1
What are starting products of synthesis of 18C sphinganine?
What is end product (initial starter molecule)?
How is this easily recognized?
Starting = Palmitoyl CoA + Serine
End Product = Ceramide
Easily recognized (unique) amide linkage on carbon #2
What is the source of the backbone in sphingomyelin?
Palmitate
Cerebroside
Sphingosine backbone with sugar unit on head–
Glucose or Galactose
Carbon #2 has fatty acid w/Amide Linkage
Ceramide + Phosphatidylcholine
Sphingomyelin
Ceramide + UDP-glucose
Cerbroside
Cerebroside + Activated Sugars
Gangliosides
Farber’s has accumulation of?
Ceramide
Tay Sachs has an accumulation of?
Gangliosides
Plasmalogen
Ether alkene phospholipid
- Prevalent in cardiac tissues
- May protect against ROS
Platelet Activating Factor
Ether Linked Alkane
Ether glycerolphspholipid
