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OVERVIEW OF LIPIDS & LIPID METABOLISM
Lecture 3 Part 2
Terms in this set (39)
What are the 4 learning objectives to know by the end of this lecture?
1) Be familiar with common lipids other than Trigycerides
2) Understand the structure and function of phospholipids and their synthesis/catabolism.
3) Know the key building blocks of sphingolipids and key aspects of their synthesis and catabolism
4) Understand the structure and function of steroids, the key aspects of cholesterol synthesis and its regulation
In the CLASSIFICATION of LIPIDS - excluding isoprenoids and steroids - what should you focus on first?
What are the 3 structural elements of GLYCERO PHOSPHOLIPIDS?
1) Head-group substituent
2) Saturated fatty acid (e.g. palmitic acid)
3) Unsaturated fatty acid (e.g. oleic acid)
Describe the very unique glycero phospholipids that some tissues in the body have
Docosahexaenoic acid (DHA) is an Omega 3 fatty acid that can be generated from alpha Linolenic acid (ALA). DHA is heavily utilized in phospholipids in the retina, sperm, testis and the cerebral cortex.
Give examples of COMMON GLYCEROPHOSPHOLIPIDS and their alcohol substituent esters
1) Phosphatidyl serine
2) Phosphatidyl choline
3) Phosphatidyl ethanolamine
4) Phosphatidyl inositol
5) Diphosphatidyl glycerol (cardiolipin)
What three glycerophospholipids are interrelated and can undergo rxns to convert to the other cmpds?
How is Cardiolipid synthesized?
Cardiolipin is synthesized from phosphatidyl-CMP and phosphatidylglycerol
What are the 6 LIPID DISTRIBUTIONs IN DIFFERENT MEMBRANES?
3) Minor Lipids
In the COMMON LIPID ANCHORS IN MEMBRANES, what lipids are found on the outside?
Glycosyl Phosphatidyl Inositol (GPI) anchors
In the COMMON LIPID ANCHORS IN MEMBRANES, what lipids are found on the inside?
Direct Acylation or Isoprenylation
The Common ones are:
1) Palmityl, Myristyl
What is the importance of Phosphatidyl Inositol?
Non covalent binding of Phosphatidyl Inositol by specialized protein domains (PH) - involved in the outside lipid anchors
What is the 1st step in the Synthesis of Glycerophospholipids?
Step 1: SYNTHESIS OF PHOSPHATIDATE and DAG
Note: Up to DAG, same as first steps in Triglyceride synthesis
What is going on in the Synthesis of Glycerophospholipids with diacylglycerol?
Phosphatidate derived diacylglycerol can be further converted through activated Diacylglycerol OR activated Substituents
In the CLASSIFICATION of LIPIDS (excluding isoprenoids and steroids) what should you focus on second?
Sphingolipids derived from both Phospholipids (PO4 a d choline) and Glycolipids (Mono or oligosaccharides)
What is common to all sphingolipids?
R group (specific to different types)
What are the TYPES OF SPHINGOLIPIDS and Substituents that you should know?
3) Ganglioside GM2
What do MOST DEFECTS OF SPHINGOLIPID METABOLISM relate to?
Most defects of sphingolipid metabolism relate to the strictly sequential mode of degradation
What is at play in Cholesterol Homeostasis?
- Primary sites of Cholesterol Production: Liver, Intestine, Adrenal Cortex, Reproductive Tissue
- The liver is the only site of regulated Cholesterol redistribution and disposal
What is happening at the Primary sites of Cholesterol Production?
1) Cholesterol is being synthesized in extrahepatic tissue - HDL
2) De novo synthesis in the liver
What is happening in the liver during regulated Cholesterol redistribution and disposal?
1) Free cholesterol secreted in the bile
2) Secretion of VLDL
3) Conversion to bile acids and bile salts
What are the 3 levels on which Cholesterol Synthesis is regulated?
1) Sterol dependent
2) Sterol independent through phosphorylation/dephosphorylation (AMP -> ATP level sensitive)
Describe Sterol dependent regulation of Cholesterol Synthesis
Sterol dependent: Stability of SREBP (+HMGCoA reductase) through ER Cholesterol levels (Destabilization)
Describe Hormonal regulation of Cholesterol Synthesis
3) Hormonal: Insulin upregulates and Glucagon down regulates HMGCoA reductase expression
- Statins act as competitive inhibitors of HMGCoA reductase
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Progesterone?
Progesterone: Female sex hormone and general precursor
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Cortisone?
Antiinflammatory Increases Gluconeo-genesis and muscle protein breakdown
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Aldosterol?
Na reabsorbtion, K secretion
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Testosterone?
male sex characteristics
based on T/E ratio
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Estrogen?
female sex characteristics based on T/E ratio
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Calcitriol?
Regulation of Calcium absorption and homeostasis
Neuromuscular and immune function (2011 update of RDA)
Serum Calcidiol (25(OH)D) is usually being measured.
When thinking about Cholesterol as the universal precursor for steroid and related hormones, what is the role of Bileacids?
Main component of bile needed for lipid absorbtion
(In addition bileacid receptors are classic steroid hormone receptors)
Where are Cortisone and Aldosterol stored and created?
In the Adrenal Gland (Adrenal Cortex)
Where are Testosterone and Estrogen stored and created?
Primarily synthesized in Gonads
Where do the bile acids come from?
What derivative of cholesterol is found in the skin?
7-Dehydrocholesterol from UV light
What derivative of cholesterol is found in the liver?
What derivative of cholesterol is found in the kidney?
Calcidiol (D2) and Calcitriol (vitamin D3)
What is the most basic description of Steroid Hormone Receptors (SHR)?
1) Hormone present
2) Steroid Hormone receptor (SHR) binds to hormone
3) Transcription of a particular gene is up-regulated
Describe in detail the first part of SHR reception before DNA transcription
Steroid Hormone Receptors (SHR) act as hormone dependent nuclear transcription factors. Upon entering the cell by passive diffusion, the hormone (H) binds the receptor (1), which is subsequently released from heat shock proteins (2), and translocates to the nucleus (3).
Describe in detail the DNA transcription process of Hormone reponse
In the cell nucleus, the receptor dimerizes (4), binds specific sequences in the DNA, called Hormone Responsive Elements (HREs) (5), and recruits a number of coregulators (7) that facilitate gene transcription (8). This latter step can be modulated by receptor antagonists like tamoxifen (T) (11), and cellular signalling pathways (6 + 10).
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