Lecture 13: tg and fa breakdown

Question 1

Triglyceride

•_____\_cleave _____\_ bonds, releasing FAs and glycerol

Answer 1

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

Question 2

60-80% of energy needs of mammalian cardiac and skeletal muscle, liver and kidney and 30% overall are met by _______

Answer 2

60-80% of energy needs of mammalian cardiac and skeletal muscle, liver and kidney are met by FA Oxidation

Question 3

_______ is major site of FA metabolism

• Synthesis of FAs
• Oxidation of FAs for energy

Answer 3

Liver is major site of FA metabolism

• Synthesis of FAs
• Oxidation of FAs for energy

Question 4

Epinephrine and glucagon stimulate TG ________\_

• Activates _____________ in adipocytes
• Hydrolyses TG’s to FA’s and Glycerol

Answer 4

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*

Question 5

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 ___________\_

Answer 5

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

Question 6

Metabolic Fates of Glycerol

Answer 6

Question 7

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 ______\_

Answer 7

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

Question 8

FA Activation: Formation of Fatty Acycl CoA

• Esterified to CoA before oxidation
• Catalysed by ________________ in the outer mitochondrial membrane

Answer 8

FA Activation: Formation of Fatty Acycl CoA

• Esterified to CoA before oxidation
• Catalyzed by Acyl-CoA Synthetase in the outer mitochondrial membrane

Question 9

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 ________________

Answer 9

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__​

Question 10

Summary of Reactions Involved in Beta-Oxidation of Fatty Acids

Answer 10

Question 11

Carnitine or Carnitine Acyl Transferase Deficiency:

• Causes?
• Clinical Manifestations?
• Treatment/Managements?

Answer 11

Question 12

The first step of beta-oxidation is catalyzed by _______________

• 3 Isomers: Long-chain, Medium-chain, short chain
• The product has a ______ double bond

Answer 12

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

Question 13

_________ __________ fatty acids constitute the majority of FA consumption

Answer 13

Medium-chain fatty acids constitute the majority of FA consumption so absence is significant

Question 14

_____________________________ Deficiency:

• intermittent hypoglycemia (low blood glucose) and coma
• intolerance to prolonged fasting
• fatigue/lethargy
• impaired ketogenesis

Answer 14

Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency:

• intermittent hypoglycemia (low blood glucose) and coma
• intolerance to prolonged fasting
• fatigue/lethargy
• impaired ketogenesis

Question 15

Complete oxidation of C16 yields:

• ___acetyl-CoA
• _____ FADH₂
• ____ NADH

Answer 15

Complete oxidation of C16 yields

• 8 acetyl-CoA
• 7 FADH2
• 7 NADH

Question 16

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.

Answer 16

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.

Question 17

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

Answer 17

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

Question 18

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 ___________

Answer 18

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_

Question 19

______________ 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 __________

Answer 19

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

Question 20

________________ Disorders: arise from a lack of _________

• Zellweger syndrome
• infantile refsum disease
• neonatal adrenoleukodystrophy

Answer 20

Peroxisomal Biogenesis Disorders: arise from a lack of peroxin

• Zellweger syndrome
• infantile refsum disease
• neonatal adrenoleukodystrophy

Question 21

Deficiency of peroxisomal FA oxidative enzymes can lead to _____________ disease from a lack of phytanic acid oxidase needed to breakdown Fatty Acids.

Answer 21

Deficiency of peroxisomal FA oxidative enzymes can lead to Adult Refsum disease from a lack of phytanic acid oxidase needed to breakdown Fatty Acids.

Question 22

X linked adrenoleukodystrophy is associated with?

Answer 22

X linked adrenoleukodystrophy is associated with :

• The absence of functional FA transporter ABCD1 and inability to transport FA’s into peroxisome
  *

Question 23

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 _________________\_

Answer 23

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)

Question 24

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

Answer 24

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

Question 25

• 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?

Answer 25

• 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

Question 26

FAs are the major energy source in almost all tissues except the _____ and ______

Answer 26

FAs are the major energy source in almost all tissues except the brain and RBCs

Question 27

FAs are oxidized by the Beta-oxidation pathway into acetyl-CoA in the ____________

Answer 27

FAs are oxidized by the Beta-oxidation pathway into acetyl-CoA in the mitochondrial matrix

Question 28

_____ and ______ formed during oxidation can yield large quantities of ATP in the electron transport chain

Answer 28

NADH and FADH₂​ formed during oxidation can yield large quantities of ATP in the electron-transport chain

Question 29

FA oxidation and synthesis are reciprocally regulated through the production of __________\_

Answer 29

FA oxidation and synthesis are reciprocally regulated through the production of malonyl CoA

Question 30

Acetyl-CoA can be either oxidized via the _________ or converted to __________ in the liver that can serve as fuel for other tissues

Answer 30

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