1 - Lipid Metabolism Flashcards
1
Q
Fat Metabolism
A
Fat metabolism is closely associated with carbohydrate metabolism
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2
Q
Fatty acids’ roles
A
- Fatty acids’ roles include the following:
- Storage/transport as triacylglycerols for fuels
- Components of membrane sphingolipids and glycerophospholipids
- Precursors of eicosanoids
- Precursors of regulatory molecules
3
Q
Saturated fatty acids
A
- Saturated fatty acids can be packed together very tightly on account of their geometry (linear and zigzagged), while unsaturated fatty acids do NOT pack well together because of their geometry (double bonds introduce bends in molecule). This explains the fact that saturated fatty acids have higher melting points than unsaturated fatty acids.
- Saturated ones can yield a lot of NADPH (a reducing agent)?
- Saturated fatty acids have no double bonds, while unsaturated have one or more double bonds. They can be mono-unsaturated or polyunsaturated fatty acids (P.U.F.A)
- Double bonds are almost always in the cis configuration
- Double bonds are spaced at intervals of three carbons
- Trans fats are the product of partial hydrogenation of cis-unsaturated fats. They have been strongly implicated in coronary heart disease and might be possibly associated with other diseases.
- Trans fats are bad in general; not found in nature
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4
Q
Classification of fatty acids
A
- In physiological systems, fatty acids are generally ionized at the ambient pH (RCOO-) and technically should be written with the suffix “ate,” not “oic acid”
- The most common fatty acid in the human are palmitic (16:0) or palmatate and stearic acid (18:0)
- Structural lipids and triacylglycerols contain primarily fatty acids of at least sixteen carbons
- Essential fatty acids:
-
Linoleic acid - 18:2 (9,12)
- Omega-6 since 18-12=6
- liNoleic (N located 6 from the end)
-
α-Linolenic acid - 18:3 (9,12,15)
- Omega-3 since 18-15=3
- linoleNic (N located 3 from the end)
- Essential fatty acids are polyunsaturated (PUFA)
- These 2 essential fatty acids are linoleic acid and α-linolenic acid
-
Linoleic acid - 18:2 (9,12)
- Precursor of postaglandins:
- Arachidonic acid - 20:4 (5,8,11,14)
- Here, the second number designate number of double bonds there are; numbers in paranphases designate the location of the double bonds
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5
Q
Lipid acid numbering
A
- Carbon 2 is known as the alpha carbon; carbon 3 is the beta carbon, and so forth
- The carbon of the terminal methyl is known as the omega (last) carbon regardless of the total length
- The asterisk (in the book) designates one of the double bonds found in omega-6 (no need to know this point)
- Dr. Marvit said we don’t have to know how to actually number any fatty acids (confirm it for me)
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6
Q
Ovierview of the lecture
A
- There are minimally 4 processes that will be discussed at length in this unit:
- Synthesis of fatty acids
- Synthesis of TAG’s
- Release of fatty acids from TAG’s
- Oxidation of fatty acids
- Unless stated otherwise, all processes discussed in this lecture are in reference to palmitate (a long-chain saturated fatty acids containing 16 carbons)
- Generally, fatty acid synthesis “de novo” (“de novo” = “from scratch”) occurs during times of excess energy. This is because fatty acids are supplied dietarily
- Major site for fatty acid synthesis is liver. Other sites include: adipose tissue, mammary gland, brain, and kidney
7
Q
Carboxylation of Acetyl-CoA
A
- The first committed step of fatty acid synthesis is the carboxylation of acetyl-CoA to malonyl-CoA
- The carboxylation of acetyl CoA yields malonyl CoA
-
Acetyl CoA carboxylase (ACC):
- Utilizes biotin
- Biotin serves as a coenzyme in other carboxylations (pyruvate carboxylase)
- Carboxylation rxn requires ATP
- Utilizes biotin
- The dimer of ACC is the inactive enzyme
- The polymer of ACC is the the active enzyme
- Citrate is involved in the fat metabolism (since it involves ATP for building things up)
- CO2 is added to Acetyl CoA and thus becomes biotin (blue-lettered part of Malonyl CoA in the figure)
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8
Q
AMP-activated protein kinase
A
- AMPK (AMP-activated protein kinase) phosphorylates ACC, thusly inactivating the enzyme
- AMP-activated means High level of AMP (or low level of ATP) activates AMPK
- Glucagon and epinephrine both inactivate ACC
- Insulin activates ACC
- What effect would elevated levels of palmitoyl-CoA have on ACC?
- Allosteric control occurs as feedback inhibition by palmitoyl-CoA and activation by citrate.
- When there are high levels of palmitoyl-CoA, the final product of saturated fatty acid synthesis, it allosterically inactivates acetyl-CoA carboxylase to prevent a build-up of fatty acids in cells.
- Citrate acts to activate acetyl-CoA carboxylase under high levels, because high levels indicate that there is enough acetyl-CoA to feed into the Krebs cycle and produce energy
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9
Q
Fatty acid synthase
A
- In bacteria, fatty acid synthesis is catalyzed by six separate enzymes, plus acyl carrier protein
- In mammals, fatty acid synthesis is catalyzed by separate domains of multi-catalytic, homo-dimeric, polypeptide, which includes acyl carrier protein
- ACP contains phosphopantetheine, a derivative of pantothenic acid
- 5-chloro-2-(2,4-dichlorophenoxy)phenol inhibts one of the bacterial enzymes associated with fatty acid synthesis
- Questions associated with the usage of this product have arisen.
- This product can be found in some:
- Soaps
- Cosmetics
- Deodorants
- Toothpastes
- Triclosan is another example where its use is being questioned; used to prevent bacterial contamination
10
Q
Elongation cycle of fatty acid synthesis
A
- Elongation cycle of fatty acid synthesis consits of 4 stages:
- Condensation of acetyl-ACP and malonyl-ACP, forming acetoacetyl-ACP
- Reduction of acetoacetyl-ACP, with the utilization of NADPH i.e. reductive =synthesis
- Dehydration
- Reduction with the utilization of NADPH
11
Q
Interrelationship between glucose metabolism and palmitate metabolism
A
(Dr. Marvit said details are not important; get the bigger picture)
- The glycolytic pathway produces pyruvate, which is the primary source of the mitochondrail acetyl CoA to be used for fatty acid synthesis. It also produces cytosolic reducing equivalents of NADH. Pyruvate enters the mitochondria
- Mitochondrial oxaloacetate (OAA) is produced by the first step in the gluconeogenic pathway
- Acetyl CoA is produced in the mitochondria and condenses with OAA to form citrate, the first step in the tricarboxylic acid cycle
- Citrate leaves the mitochondria and is cleaved in the cytosol to produce cytosolic acetyl CoA
- Cytosolic reducing equivalents (NADH) produced during glycolysis contribute to the reduction of NADP+ to NADPH needed for palmitoyl CoA synthesis
- The carbons of cytosolic acetyl CoA are used to synthesize palmitate, with NADPH as the source of reducing equivalents for the pathway
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12
Q
Generation of NADPH from NADH
A
Understand the bigger picture first
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13
Q
Palmitate
A
- Palmatate (Palmitic acid)
- Excess carbohydrates in the body are converted to palmitic acid.
- Palmitic acid is the first fatty acid produced during fatty acid synthesis and the precursor to longer fatty acids.
- As a consequence, palmitic acid is a major body component of animals
- Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC), which is responsible for converting acetyl-CoA to malonyl-CoA, which in turn is used to add to the growing acyl chain, thus preventing further palmitate generation.
- Palmitate (palmitic acid) can undergo:
- Elongation in the smooth endoplasmic reticulum
- 16, 18, 20, etc… can be elongated
- Desaturation in the smooth endoplasmic reticulum i.e. double bond formation
- Incorporation into TAG
- Elongation in the smooth endoplasmic reticulum
14
Q
Triacylglyceride (TAG)
A
- Typically TAG consist of the following:
- Fatty acid at carbon 1 is saturated
- Fatty acid at carbon 2 is unsaturated
- Fatty acid at carbon 3 can be either saturated or unsaturated
- Synthesis of TAG’s can occur in both liver and adipose tissue
- The glycerol released during TAG degradation can NOT be metabolized by adipocytes because they apparently lack glycerol kinase.
- Rather, glycerol is transported through the blood to the liver, where it can be phosphorylated. The resulting glycerol phosphate can be used to form TAG in the liver, or can be converted to DHAP by reversal of the glycerol phosphate dehydrogenase reaction; DHAP can
participate in glycolysis or gluconeogenesis.
- Most of the TAG in the body is stored in adipocytes. The liver packages the TAG into VLDL (very low density lipoprotein), which it secretes into the bloodstream and delivers to peripheral tissues
- Implications with child development at starvation state
- Chylomicron is another type of lipoprotein
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15
Q
Glycerol
A
- Glycerol can serve as the starting material for gluconeogenesis
- In both liver and adipose tissue, glycerol phosphate can be produced from dihydroxyacetone phosphate (DHAP), an intermediary of glycolysis
- The liver utilizes glycerol kinase to produce glycerol phosphate from glycerol. Glycerol kinase is not found in adipose tissue
- The glucose transporter in adipocytes, GLUT-4, is insulin-dependent. What does this mean?
- (Hint: if you answered that adipose production of TAG is controlled by plasma levels of glucose, you would be CORRECT)
- Please remember that glycerol can serve as the starting material for gluconeogenesis. Please explain.–> *refer to the very first card*
- The fact that there is glycerol in your system may be indicative of you being in starvation state where gluconeogenesis kicks in to make glucose
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