Term
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Definition
| The breakdown of triacylglycerol stores in the adipose tissue |
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Term
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Definition
| C16:0 (hexadecanoic acid) |
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Term
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Definition
| C18:0 (octadecanoic acid) |
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Term
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Definition
| C18:1 (9) [cis-9-octadecenoic] |
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Term
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Definition
| C18:2 (9,12) [all cis 9,12-octadecadienoic acid] |
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Term
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Definition
| C18:3(9,12,15) [all cis-9,12,15-octadecatrienoic] |
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Term
| What is arachidonic acid? |
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Definition
20:4(5,8,11,14)[all cis5,8,11,14eicosatetraenoic]
Arachidonic acid can be synthesized, synthesis depends on the adequate linoleic acid in the diet. |
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Term
| What are essential fatty acids? |
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Definition
Fatty acids where mammalian tissues can not insert the double bonds in the correct location
Linoleic acid and linolenic acid are essential FA's |
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Term
| What are some important properties of triacylglycerols? |
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Definition
TG are formed from FA’s derived either from hydrolysis of dietary fat or from synthesis are transported to and stored in adipose tissue.
TG's are in insoluble in water and has very little associated water. Thus, the storage form of lipids takes up less volume than does the storage of an equal amount of carbohydrate.
TG’s are a major source of caloric energy yielding 9 Kcal/gm compare to 4 Kcal/gm of protein or carbohydrate. This high energy value is due to the lower oxidation state of the hydrocarbon chains of fatty acids.
TG's insulates the body against heat loss, forms a protective cushion for many tissues organs, and constitutes 10% of the body weight of a normal adult. |
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Term
| What is the role of glucagon in lipolysis? |
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Definition
Glucagon is a positive effector of adenyl cyclase
Adenyl cyclase changes ATP to cAMP
cAMP is a positive effector of cAMP-dependent protein
kinase
cAMP-dependent protein kinase activates hormone-sensitive lipase a
hormone sensitive lipase a is the primary enzyme of lipolysis
increased glucagon leads to increased lipolysis |
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Term
| What is the role of EPI and NE in lipolysis? |
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Definition
EPI and NE are positive effectors of adenyl cyclase
Adenyl cyclase changes ATP to cAMP
cAMP is a positive effector of cAMP-dependent protein
kinase
cAMP-dependent protein kinase activates hormone-sensitive lipase a
hormone sensitive lipase a is the primary enzyme of lipolysis
increased EPI and NE levels lead to increased lipolysis |
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Term
| What is the role of insulin in lipolysis? |
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Definition
Insulin inhibits lipolysis
Insulin is a positive effector of phosphodiesterase which changes cAMP to AMP
This decreases cAMP-dependent protein kinase A activity which will in turn decrease hormone-sensitive lipase a activity.
Insulin also ca inhibit the gene expression of hormone-sensitive lipase a |
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Term
| How do FFA's affect lipolysis? |
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Definition
FFA's are negative effectors
FFA's can inhibit hormone-sensitive lipase a directly (product inhibition)
FFA's also inhibit adenyl cyclase. This leads to decreased cAMP then decreased cAMP-dependent protein kinase activity then decreased hormone-sensitive lipase a activity. |
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Term
| What happens to free fatty acids after they are produced by triacylglycerol breakdown? |
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Definition
TG hydrolysis by adipose tissue releases free fatty acids into the plasma, where they bind to serum albumin (weak binding)
Albumin-bound FA are transported in the circulation until FA are taken up by tissues (including liver, heart, kidney, muscle, lung, testis, and adipose tissue, but not readily by brain - brain is the only tissue that does not take up FFA)
In the tissues, they are either oxidized or re-esterified.
The utilization of glycerol depends upon whether such tissues possess glycerol kinase, found in significant amounts in liver, kidney, intestine, brown adipose tissue, and lactating mammary gland. |
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Term
| What is the role of carnitine palmitoyl transferase 1 (CPT I) in fatty acid metabolism? |
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Definition
It is used in tandem with CPT II to transfer acyl CoA from the cytosol to the mitochondrial matrix
The step involving CPT I (transferring the acyl group onto carnitine) is the regulatory or rate limiting step |
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Term
| What are the important concepts of beta-oxidation? |
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Definition
- occurs in the mito. matrix
- each cylce of the pathway produces acetyl CoA, NADH, FADH2
- each cycle removes two C's from the chain and the final product is a two C carbon (acetyl Coa), thus a C16 carbon will go through 7 cycles
- NO ATP is used nor produced |
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Term
| What are the different enzymes in beta oxidation? |
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Definition
Acyl CoA dehydrogenase (several chain length specific versions)
enoyl CoA hydratase
l-beta-hydroxyacyl-CoA dehydrogenase
acetyl CoA lyase (thiolase) |
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Term
| Explain long‑chain acyl‑CoA dehydrogenase (LCAD) deficiency |
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Definition
Affects the beta oxidation of fatty acids with more than 12 carbons
Symptoms - Appears in infancy, infants show failure to thrive, hepatomegaly, nonketotic hypoglycemia |
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Term
| Explain medium‑chain acyl‑CoA dehydrogenase (MCAD) deficiency |
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Definition
Affects beta oxidation of fatty acids with 6-12 carbons
Symptoms - The most common deficiency, mild myopathy starting in childhood |
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Term
| Explain short‑chain acyl‑CoA dehydrogenase (SCAD) deficiency |
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Definition
Affects beta oxidation of fatty acids with less than 6 carbons
symptoms - very rare deficiency, some infants have failure to thrive and nonketotic hypoglycemia, myopathy in a few patients |
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Term
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Definition
Carnitine Palmitoyl Transferase Deficiency (CPT) is an inherited fatty acid oxidation disorder.People with CPT cannot properly break down fats to energy.
There are two forms of this disorder: Carnitine palmitoyltransferase I (CPT-I) Carnitine palmitoyltransferase II (CPT-II)
These result from mutations in the CPT1 and CPT2 genes giving defective versions of each enzyme.
CPT is inherited in an autosomal recessive manner, meaning that a person affected with CPT must inherit two mutated copies of the CPT gene. Usually, both parents are carriers who have one working and one defective copy of the gene.
Typically, there is no family history of CPT in an affected person.
CPT is a rare fatty acid oxidation disorder; the total number of people affected with CPT is not known. |
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Term
| How is beta-oxidation of FA's regulated? |
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Definition
Overall a high energy ratio inhibits the beta-oxidation of FA
A high ATP/ADP inhibits the ETC.
Inhibition of the ETC leads to increased levels of NADH and FADH2
Increased levels of NADH and FADH2 inhibit the beta-oxidation pathway |
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Term
| How does beta-oxidation of odd chain FA's differ from normal beta-oxidation? |
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Definition
Odd-chain fatty acids produce propionyl CoA in addition to acetyl CoA
In odd chain FA beta-oxidation the last step is now going from a C5 to a C3 and a C2 (as opposed to the normal C4 to two C2's)
Propionyl CoA is the C3 |
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Term
| How does beta-oxidation of unsaturated FA's differ from normal beta-oxidation? |
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Definition
Unsaturated fatty acids require one or two additional enzymes in order for double bonds to moved into the right positions for the products to continue in ß-oxidation:
1) Δ4cis-Δ2trans enoyl CoA isomerase
2) Δ3trans-Δ4cis-dienoyl CoA reductase |
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Term
| What is alpha-oxidation of FA? |
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Definition
The removal of one carbon units as CO2 from the carboxy terminal of FAs.
The first step in alpha-oxidation is the hydroxylation of the alpha-C (the #2 C). This process requires oxygen, Fe2+ and ascorbic acid.
Alpha-oxidation is important in the oxidation of both branched chain and odd chain fatty acids. It occurs in mitochondria and in the endoplasmic reticulum (microsomes). |
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Term
| What is Refsum's disease? |
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Definition
| It results from an inability to oxidize highly branched chain fatty acids (e.g., phytanic acid) due to a genetic deficiency in the α-oxidation system, and can result in a storage disorder. |
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Term
| How is alpha-oxidation of a branched chain FA related to beta-oxidation? |
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Definition
| After alpha-oxidation subsequent ß-oxidation of the branched chain FA will give propionyl CoA wherever there was a branching methyl group. Hence branch chain FA are glucogenic and ketogenic, like odd-chain FA. |
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Term
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Definition
| This type of oxidation involves the hydroxylation of the terminal methyl group of a fatty acid or branched chain amino by a mixed function oxidase requiring NADPH and Cytochrome P-450 in microsomes. This results in the formation of a primary alcohol which is subsequently oxidized to a carboxy acid which requires two oxidation steps and H2O. |
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Term
| What is dicarboxylic acidosis? |
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Definition
Individuals excrete medium chain dicarboxylic acid due to a deficiency in mitochondrial medium chain acyl CoA dehydrogenase.
These dicarboxylic acids include adipic (C6), suberic (C8), sebacic (C10), and dodecanedioic (C12). Each is formed by omega-oxidation in an attempt, without success, to begin oxidation at the opposite end of the fatty acid.
These omega-oxidation products appear in urine and a diagnosis can be made expeditiously |
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Term
| What is peroxisomal fatty acid oxidation |
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Definition
Peroxisomal fatty acid oxidation has the same sequence of reactions as does beta-oxidation by mitochondria (activation, desaturation, hydration, dehydrogenation and thiolysis).
The enzymes are quite different however. The most important change in peroxisomal oxidation is the use of a FAD linked Acyl CoA dehydrogenase (oxidase) which transfers the electrons and hydrogens directly to diatomic oxygen. This results in the formation of H2O2.
The enzymes in the peroxisomes do not oxidize fatty acids with chain lengths less than eight. Thus ocatanoyl CoA and four acetyl CoA are the products of oxidation of palmitoyl CoA. |
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Term
| What is Zwellweger's syndrome? |
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Definition
| An inherited absence of peroxisomes (in all tissues) leading to the accumulation long chain polyenoic acids in brain tissues. |
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Term
| What are the basics behind ketone metabolism? |
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Definition
Acetoacetate and ß-hydroxybutyric acid are synthesized in the liver from acetyl CoA
3 acetyl CoA's lead to one HMG-CoA which leads to acetoacetate which can be reduced by NADH to form ß-hydroxybutyric acid
These ketone bodies leave the mitochondrion and the liver cell by diffusion and enter the blood. They can be utilized by brain, heart, and muscle |
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Term
| What are the different possible problems with ketone body metabolism? |
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Definition
ketonemia - increased blood ketone bodies
ketonuria - level of ketone bodies high enough that they appear in urine
ketosis - level of ketone bodies higher than ability of tissues to utilize them
ketoacidosis - level of ketone bodies higher than the blood buffering capacity and blood pH falls - this is the most sever problem, occurs in diabetics because they have increased FA oxidation |
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Term
| What are the important concepts behind the net yield of ATP from fatty acids? |
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Definition
FA oxidation creates several different products that can lead to ATP production
NADH and FADH2 which can be used in the ETC
Acetyl CoA which can be oxidized in the TCA cycle and then coupled to the ETC
the amount of double bonds in the FA affects the gross yield
the net yield is always 2 ATP less (per FA) than the gross yield because 2 ATP are needed in the activation of FA to FA-CoA. glycerol uses 1 ATP |
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Term
| Why is it important for acetoacetate to be reduced to beta-hydroxybutyric acid? |
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Definition
| Acetoacetate can spontaneously form acetone which is not utilized by any of the tissues |
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Term
| Explain the transport of fatty acids and triacylglycerols in the circulation |
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Definition
FA's can leave the adipose tissue as FFA and can enter the liver or muscle tissue
TG's from the liver or the small intestine can be in the blood plasma and lipoprotein lipase metabolizes them into FA's at the adipose tissue and/or muscle. |
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