Lecture 13: tg and fa breakdown Flashcards
Triglyceride
•_____\_cleave _____\_ bonds, releasing FAs and glycerol
Triglycerides
- storage form of FAs (glycerol esterified to 3 FAs)
- stored mainly in adipose tissue (much smaller deposits in muscle and liver)
- lipases cleave ester bonds, releasing FAs and glycerol
60-80% of energy needs of mammalian cardiac and skeletal muscle, liver and kidney and 30% overall are met by _______
60-80% of energy needs of mammalian cardiac and skeletal muscle, liver and kidney are met by FA Oxidation
_______ is major site of FA metabolism
- Synthesis of FAs
- Oxidation of FAs for energy
Liver is major site of FA metabolism
- Synthesis of FAs
- Oxidation of FAs for energy
Epinephrine and glucagon stimulate TG ________\_
- Activates _____________ in adipocytes
- Hydrolyses TG’s to FA’s and Glycerol
Epinephrine and glucagon stimulate TG Lipolysis:
- Activates hormone-sensitive lipase in adipocytes
- Hydrolyses TG’s to FA’s and Glycerol
- Epinephrine: Energy needed immediately*
- Glucagon: no more glucose*
- Insulin: Plenty of energy available, no need to breakdown reserves*
Triglyceride Breakdown in Adipose Tissues:
- An increase in ____\_ activates protein kinase A:
- Activates __________________\_
- Phosphorylates perilipin
- Hormone-Sensitive Lipase gains access to liquid droplet and hydrolysis TG’s releasing Fatty Acids and Glycerol
- FA’s leave adipocyte bound to ___________\_
Triglyceride Breakdown in Adipose Tissues:
- An increase in cAMP activates protein kinase A:
- Activates Hormone-Sensitive Lipase
- Phosphorylates perilipin
- Hormone-Sensitive Lipase gains access to liquid droplet and hydrolysis TG’s releasing Fatty Acids and Glycerol
- FA’s leave adipocyte bound to Serum Albumin
Metabolic Fates of Glycerol
Overview of Beta- Oxidation of FA’s
- FA oxidation occurs in ____________\_
- FAs are activated by linkage to CoA-SH forming fatty acyl CoA
- Occurs _______________________\_
- Oxidized by recurring series of 4 reactions yielding ________\_ for TCA
- Each cycle of 4 reactions generates 1 _____\_and 1 ______\_
Overview of Beta- Oxidation of FA’s
- FA oxidation occurs in Mitochondrial Matrix
- FAs are activated by linkage to CoA-SH forming fatty acyl CoA
- Occurs Outside Mitochondrial matrix
- Oxidized by recurring series of 4 reactions yielding 2C Acycl CoA
- Each cycle of 4 reactions generates 1 NADH and 1 FADH2
FA Activation: Formation of Fatty Acycl CoA
- Esterified to CoA before oxidation
- Catalysed by ________________ in the outer mitochondrial membrane
FA Activation: Formation of Fatty Acycl CoA
- Esterified to CoA before oxidation
- Catalyzed by Acyl-CoA Synthetase in the outer mitochondrial membrane
Fatty Acyl CoA Transport into Mitochondrial Matrix:
- Short-chain fatty acyl less than ______ can freely diffuse into the matrix
- Longer fatty acids must be transported by ________________
Fatty Acyl CoA Transport into Mitochondrial Matrix:
- Short-chain fatty acyl less than 12 Carbons can freely diffuse into the matrix
- Long fatty acids must be transported by Acyl-carnitine / Carnitine Transporter__
Summary of Reactions Involved in Beta-Oxidation of Fatty Acids
Carnitine or Carnitine Acyl Transferase Deficiency:
- Causes?
- Clinical Manifestations?
- Treatment/Managements?
The first step of beta-oxidation is catalyzed by _______________
- 3 Isomers: Long-chain, Medium-chain, short chain
- The product has a ______ double bond
The first step of beta-oxidation is catalyzed by acyl-CoA dehydrogenase
- 3 Isomers: Long-chain, Medium-chain, short chain
- The product has a Trans double bond
_________ __________ fatty acids constitute the majority of FA consumption
Medium-chain fatty acids constitute the majority of FA consumption so absence is significant
_____________________________ Deficiency:
- intermittent hypoglycemia (low blood glucose) and coma
- intolerance to prolonged fasting
- fatigue/lethargy
- impaired ketogenesis
Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency:
- intermittent hypoglycemia (low blood glucose) and coma
- intolerance to prolonged fasting
- fatigue/lethargy
- impaired ketogenesis
Complete oxidation of C16 yields:
- ___acetyl-CoA
- _____ FADH2
- ____ NADH
Complete oxidation of C16 yields
- 8 acetyl-CoA
- 7 FADH2
- 7 NADH
Oxidation of glucose through glycolysis, TCA cycle, & oxidative phosphorylation yields about _____\_ATP
Beta Oxidation of C16 Fatty acid yields __\_ATP and its products go on to yield a total of ___\_ ATP.
Oxidation of glucose through glycolysis, TCA cycle, & oxidative phosphorylation yields about 30-32 ATP
Beta Oxidation of C16 Fatty acid yields 28 ATP and its products go on to yield a total of 108 ATP.
Beta Oxidation of Odd numbered Carbon FA’s
- Beta oxidation as normal until 3 carbon segment _______ is reached
- A carboxyl group is then added to create the 4 carbon group _______, a TCA intermediate
Beta Oxidation of Odd numbered Carbon FA’s
- Beta oxidation as normal until 3 carbon segment propionyl-CoA is reached
- A carboxyl group is then added to create the 4 carbon group succinyl-CoA, a TCA intermediate
Oxidation of MUFAS and PUFAS
- Normal beta-oxidation until first C=C bond reached
- Natural cis double bonds must first be converted to trans isomer by _________\_
- In PUFA, Second C=C results in a trans, cis configuration which must be reduced to a single trans isomer by ___________
Oxidation of MUFAS and PUFAS
- Normal beta-oxidation until first C=C bond reached
- Natural cis double bonds must first be converted to trans isomer by Enoyl-CoA Isomerase
- In PUFA, Second C=C results in a trans, cis configuration which must be reduced to a single trans isomer by D_ienoylCoA reductase_
______________ Beta Oxidation:
- Important for oxidation of long or branched-chain FAs
- Transported to membrane-bound organelles rich in oxidative enzymes
- Acetyl CoA is exported and can be oxidized in the TCA cycle
- Once linear chair 18C or less exported for Beta-Xoidation in __________
Peroxisomal Beta Oxidation:
- Important for oxidation of long or branched-chain FAs
- Transported to membrane-bound organelles rich in oxidative enzymes
- Acetyl CoA is exported and can be oxidized in the TCA cycle
- Once linear chair 18C or less exported for Beta-Oxidation in Mitochondria
________________ Disorders: arise from a lack of _________
- Zellweger syndrome
- infantile refsum disease
- neonatal adrenoleukodystrophy
Peroxisomal Biogenesis Disorders: arise from a lack of peroxin
- Zellweger syndrome
- infantile refsum disease
- neonatal adrenoleukodystrophy
Deficiency of peroxisomal FA oxidative enzymes can lead to _____________ disease from a lack of phytanic acid oxidase needed to breakdown Fatty Acids.
Deficiency of peroxisomal FA oxidative enzymes can lead to Adult Refsum disease from a lack of phytanic acid oxidase needed to breakdown Fatty Acids.
X linked adrenoleukodystrophy is associated with?
X linked adrenoleukodystrophy is associated with :
-
The absence of functional FA transporter ABCD1 and inability to transport FA’s into peroxisome
*
Regulation of FA Oxidation:
- __________(a precursor for FA synthesis) inhibits _______\_ and thus reduces FA entry into mitochondria, reducing rate of FA oxidation
- Insulin ______ and glucagon _____ malonyl-CoA levels respectively by regulating activity of enzyme _________________\_
Regulation of FA Oxidation:
- Malonyl-CoA (a precursor for FA synthesis) inhibits carnitine acyltransferase I and thus reduces FA entry into mitochondria
- Insulin Increases and glucagon Decreases malonyl-CoA levels respectively by regulating the activity of enzyme acetyl CoA carboxylase(ACC)
Excess Acetyl-CoA produced by FA oxidation can be converted to Acetoacetate and Beta-hydroxy-butyrate also known as ___________:
- formed mainly in ______ _______
- Increased production during prolonged fasting, carbohydrate deprivation, and in some metabolic disorders such as _________\_
- Ketones can be taken up by cells, brain, and heart, in particular, converted back into Acetyl CoA which can then re-enter the TCA. Very important for _________ as it cannot take up fatty acids.
- Are _______ soluable
- The smell of _______ on breath indicative of ketoacidosis
Excess Acetyl-CoA produced by FA oxidation can be converted to Acetoacetate and Beta-hydroxybutyrate are also known as Ketones:
- formed mainly in Liver Mitochondria
- Increased production during prolonged fasting, carbohydrate deprivation, and in some metabolic disorders such as type 1 diabetes
- Ketones can be taken up by cells, brain, and heart, in particular, converted back into Acetyl CoA which can then re-enter the TCA. Very important for the brain as it cannot take up fatty acids.
- Are water soluble
- In ____________\_ due to impaired glucose uptake due to insulin deficiency cells are ‘starved’
- cells switch metabolism to gluconeogenesis and fat/protein catabolism
- excess acetyl-CoAshunted towards ketone body formation _______\_
- excessive levels of Acetoacetate and Beta-hydroxybutyrate lower blood pH dangerously (______\_) and increase _________\_ of plasma
- A clinical way to easily diagnose?
- In type 1 diabetes due to impaired glucose uptake due to insulin deficiency cells are ‘starved’
- cells switch metabolism to gluconeogenesis and fat/protein catabolism
- excess acetyl-CoAshunted towards ketone body formation Ketogenesis
- excessive levels of Acetoacetate and Beta-hydroxybutyrate lower blood pH dangerously (acidosis) and increase osmolarity of plasma
- Acetone can be detected on the breath of type I diabetics
FAs are the major energy source in almost all tissues except the _____ and ______
FAs are the major energy source in almost all tissues except the brain and RBCs
FAs are oxidized by the Beta-oxidation pathway into acetyl-CoA in the ____________
FAs are oxidized by the Beta-oxidation pathway into acetyl-CoA in the mitochondrial matrix
_____ and ______ formed during oxidation can yield large quantities of ATP in the electron transport chain
NADH and FADH2 formed during oxidation can yield large quantities of ATP in the electron-transport chain
FA oxidation and synthesis are reciprocally regulated through the production of __________\_
FA oxidation and synthesis are reciprocally regulated through the production of malonyl CoA
Acetyl-CoA can be either oxidized via the _________ or converted to __________ in the liver that can serve as fuel for other tissues
Acetyl-CoA can be either oxidized via the citric acid cycle or converted to ketone bodies in the liver that can serve as fuel for other tissues
