Exam 4 L2: TAG Degradation Flashcards
Explain what Glucagon and Epi do overall to lipid metabolism
Think: this means ____ state, so TAGS will be ______
Glucagon and Epi: think fasted state
TAGs will be mobilized into Fatty Acyl-CoA’s by the enzyme HSTL.
Then through beta oxidation, the fatty acyl CoA’s will be turned into Acetyl CoA by carinitine palmitoyltransferase I (rate limiting enzyme).
Then acetyl-coA can be turned into ketone bodies by an enzyme present only in the mitochondria: HMG-COA synthase
Triacylglycerols:
- Account for ____ of dietary fat
(Glycerol>>>>> Glucose)
- FAs account for ____ of biologically available energy
- Dietary TAG consumption should be less than ____ total calories
- Most of the TAG-FA’s is ____
TAGs:
Account for 90-95% of dietary fat
FAs account for 95% of biologically available energy
Dietary TAG consumption should be less than 30% of total calories
46% of TAG-FAs is oleic acid (18:1)
When there is a need for substrates for energy production (ATP) fatty acids are mobilized from _______
When there is a need for substrates for energy production (ATP) fatty acids are mobilized from adipose tissue TAGs
HSTL is activated by ______
_____ is phosphorylated at the same time. This is necessary for HSTL to translocate to the surgace of fat droplet and hydrolyze TAGs
(Explain what HSTL does)
HSTL: activated by cAMP-dependent protein kinase A.
HSTL takes TAGS and clips them into glycerol (which can go to gluconeogenesis) AND Fatty Acids, which become “free fatty acids” within the bloodstream and bind to albumin.
Perilipin is phosphorylated at the same time; this is necessary for HSTL to translocate to surface of fat droplet and hydrolyze TAGs.
Explain insulin vs epinephrine’s effects on HSTL
Think about this intuatively
Insulin is an inhibitor of HSTL (we already have enough energy available why would we start to breakdown TAGs)
Epinephrine is an activator of HSTL. We need energy, so we will breakdown TAGs
_____ is a major activator of HSTL
____ is also an activator of HSTL
_____ and ____ are permissive. That means they don’t activate the enzyme but their presence is needed for normal function.
______ and ____ inhibit HSTL activity
Epinephrine is a major activator of HSTL
ATCH is also an activator of HSTL
Thyroid hormone and adrenal cortical hormones are permissive.
Prostaglandins (PGE) and insulin inhibit HSTL (called “anti-lipolytic”
Fates of the Products of TAG Breakdown:
Released FAs:
- Enter the ____
- Bind to ____
- Are carried to ___
- For ___ and ___
Released glycerol:
- Is transported to the ___ and ___
Glycerol kinase phosphorylates glycerol to glycerol-3-P, which can be used in _____
Fates of the Products of TAG Breakdown:
Released Fatty Acids: Enter the bloodstream, bind to albumin, are carried to muscle, liver, etc, for beta oxidation and energy production
Released Glycerol: is transported to liver and kidney, glycerol kinase phosphorylates it into glycerol-3-P, which can be used in gluconeogenesis
Epinephrine ______ HSTL and mobilizes ______ from _____
Epinephrine activates HSTL and mobilizes fatty acids from adipose tissue TAGs
Mobilization of Fatty Acids from Adipose Tissue Influences what pathways?
Mobilization of FAs from Adipose TAGs influences:
- Fatty acid oxidation
- Ketone body formation
- Fatty acid biosynthesis
- Glycolysis (muscle)
- Gluconeogenesis (liver)
Epinephrine activates HSTL, which then breaks down TAGs into glycerol and FA’s:
What happens to the following processes:
Fatty Acid Biosynthesis
Beta-Oxidation of FA’s
Ketone Body Formation
Glycolysis
Gluconeogenesis
Fatty Acid Biosynthesis: INHIBIT
Beta Oxidation of FA’s : Increased
Ketone Body Formation: Increased
Glycolysis: Inhibit
Gluconeogenesis: Increased
So it inhibits both fatty acid biosynthesis and glycolysis
And it increases beta-oxidation of fatty acids, ketone body formation, and gluconeogenesis
Where does Beta-Oxidation of Fatty Acids occur?
Beta-Oxidation of fatty acids occurs in the mitochondria
What is the MAJOR energy-producing (ATP-producing) pathway in the body?
Mitochondrial Beta-Oxidation of Fatty Acids
What are good users of fatty acids:
1.
2.
3.
4.
Good users of fatty acids:
- Liver
- Kidney cortex
- Heart.
- Skeletal Muscle
Tissues that do not or cannot use FA’s as energy:
1.
2.
3.
4.
5.
RBCs
Brain
Nervous System
Adrenal Medulla
Lens
ALL cannot use FA’s as energy sources
Stoichiometry check:
Using 1 Palmitoyl CoA…. how many acetyl coA’s do you synthesize, and how many ATP do you get?
The complete oxidation of palmitate yields ____ ATP
1 Palmitoyl CoA (16 carbon molecule)
uses 7 FAD, 7 NAD+, 7 CoA’s and some water to form
8 Acetyl Co-A’s and 106 ATP’s
Each cycle of beta-oxidation generates:
___ Acetyl-CoA
__ NADH
__ FADH2
Each cycle of beta-oxidation generates
1 Acetyl CoA
1 NADH
1 FADH2
How do the long chain fatty acids get into the mitochondria for beta oxidation?
Inhibition of this transport results in:
1.
2.
Carnitine transports long chain fatty acids into the mitochondrial matrix for beta-oxidation
Inhibition of this transport results in:
- Inhibition of Fatty Acid Oxidation
- Decreased Production of ATP
Explain the functions of CPT-1 and CTP-II
CPT-1: takes fatty acyl group and transports the acyl group onto carnitine within the mitochondria inner layer (making acylcarinitine)
Then, a translocase brings it into the mitochondrial matrix where CPTII can transport the acyl group from acylcarnitine back onto CoASH so that it can undergo beta oxidation
What is the only known inhibitor of CPT-1?
The only known inhibitor of CPT-I is malonyl coA
This makes sense because malonyl coA is a sign that fatty acids are being synthesized, so energy is up, you wouldn’t need to break down FA’s for beta oxidation
When the liver is actively synthesizing FAs… a concurrent decrease in beta-oxidation is due to…
Inhibition of translocation between cellular compartments
Inhibition of CPT1 by malonyl coA
Malonyl coA is the product of the rxn catalyzed by _____, the rate limiting step in FA biosynthesis
Increased Malonyl CoA _____ CPT-I and ____ beta oxidation of fatty acids
Decreased Malonyl CoA ____ fatty acid oxidation
Malonyl CoA is the product of the reaction catalyzed by Acetyl-CoA Carboxylase, the rate limiting enzyme in fatty acid biosynthesis
Increased Malonyl-CoA inhibits CPT-1 and inhibits Beta oxidation of fatty acids
Decreased Malonyl coA increases fatty acid oxidation
For Beta Oxidation of Fatty Acids, what are the four general steps?
- oxidation
- hydration
- oxidation
- cleavage (by the enzyme thiolase)
Deficiency of _________ accounts for as much as 10% of sudden infant death syndrome (SIDS)
Deficiency of medium chain FA-CoA dehydrogenase
Ketone bodies are formed in the ____ when there is a high rate of ______
Ketone bodies are formed in the liver mitochondria when there is a high rate of beta oxidation of fatty acids
Explain how ketone bodies are synthesized from acetyl coA in liver mitochondria
Acetoacetyl-coA plus an acetyl-coA are added together by HMG Co-A Synthase to create HMG-CoA
Then that gets turned into acetoacetate and finally beta-hydroxybutarate
Explain what happens during ketone body utilization
Ketone bodies are made in liver, NOT used by liver
In tissues where ketone bodies are used, thiophorase transfers coA from succinyl coA onto acetoacetate, making acetoacetyl coA
The rate limiting enzyme in ketone biosynthesis is mitochondrial _______
The key enzyme in UTILIZATION of ketone bodies is ______, which transfers CoA from succinyl coA onto acetoacetate
The rate limiting enzyme in ketone biosynthesis is mitochondrial HMG-CoA Synthase (this is found only in the liver)
The key enzyme in the utilization of ketone bodies is Thiophorase, which transfers CoA from succinyl coA onto acetoacetate. Thiophorase is NOT found in the liver.
Epi will ______ the mobilization of FA’s from TAG
Insulin will _____ the mobolization of FA’s from TAG
Epi will INCREASE the mobolization of FA’s from TAG
Insulin will inhibit it
Citrate and Insulin _______ to FA synthesis via the enzyme acetyl-coA carboxylase
Glugacon and Epi _____ the beta-oxidation of fatty acids to form ketone bodies via the enzyme ___
Citrate and insulin increase FA synthesis via the enzyme acetyl coA carboxylase
Glucagon and Epi (need energy) will INCREASE the beta oxidation of fatty acids by activating CPT-1
Glucagon and Epi will _____ fatty acid biosynthesis
Glucagon and Epi will inhibit synthesis of fatty acids because you NEED energy (want to break them down)
This is due through inhibition of acetyl coA carboxylase
The only known inhibitor of CPT-1 is _____
Which is the product of ____
Therefore insulin indirectly ______
The only known inhibitor of CPT-1 is malonyl coA
Which is the product of the rate limiting enzyme in fatty acid biosynthesis (acetyl coA carboxylase)
Therefore, insulin (which promotes fatty acid biosynthesis) will indirectly inhibit (downstream) beta oxidation of fatty acids
