Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MET1 > Fat Metabolism > Flashcards

Fat Metabolism Flashcards

1
Q

How much fat do most people store and where?

A
  • Most energy in the body is actually stored in fats – most people store between 5 and 20 kg of fat in their adipose tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are important stores of energy in the body and why?

A
  • Lipids and their derivatives (ketone bodies) are important stores of long-term energy.
  • Lipids: great storage – high density energy in relatively small space and limitless storage capacity.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where and when does lipolysis occur?

A
  • Lipolysis occurs mostly in adipose tissue.

- Only occurs in aerobic conditions – needs oxygen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the main enzyme that regulates lipolysis? What is it activated/inhibited by? What controls its switching, and what can block this?

A
  • Hormone-sensitive lipase (HSL: aka diglyceride lipase)
    o Activated by adrenaline and noradrenaline (epinephrine and norepinephrine)
    o Inhibited by insulin
    o Switching is controlled by cAMP signalling that activates kinases to phosphorylate HSL which becomes active and degrades triglycerides to fatty acids.
    o Insulin blocks cAMP activity and keeps HSL de-phosphorylated (inactive)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why must there be more than one enzyme controlling lipolysis?

A
  • Experiments with knock out mice with no active HSL still are able to break down lipids…there must be more control!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What other enzyme has been identified as controlling lipolysis? What does it do and how is it regulated?

A

Adipose triglyceride lipase (ATGL)
o Breaks down triglycerides to diglycerides and fatty acid
o An important pre-cursor to HSL which is able to free up fatty acids from lipids.
- ATGL is regulated separately from HSL and is regulated and activated by glucagon via cAMP
- ATGL is also found in low levels in other tissues such as heart.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why are free fatty acids dangerous and how do we get around that?

A
  • Free FA in blood are toxic so have to be transported attached to albumin.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are fatty acids converted to acetyl Co-A?

A
  • The conversion of FA to acetyl CoA is a 3-step process:
    1. Conversion of FA -> fatty acyl-CoA on outer mitochondrial membrane
    o (enzyme: acyl CoA synthase [ACS])
    o uses ATP -> AMP
    1. Fatty acyl CoA transported into mitochondrial matrix by the Carnitine shuttle
    1. Beta-oxidation of fatty acyl-CoA to acetyl CoA + NADH/FADH2 (Krebs cycle….)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What happens in the Carnitine Shuttle?

A
  • Fatty acyl Co-A is linked to a carnitine molecule (enzyme – carnitine acyl-transferase I [CATI]). CoA is released.
  • Acyl-carnitine complex transferred across IMM into the matrix (enzyme – translocase)
  • Acyl-carnitine reacted with CoA to produce acyl-CoA inside the matrix and carnitine shuttled back out (enzyme – carnitine acyl transferase II, CATII)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When does the main regulation of FA metabolism occur? How is transport of FA into the mitochondria inhibited/activated?

A
  • Main regulation of FA metabolism occurs during the carnitine shuttle.
  • Transport of FA into the mitochondria:
  • Inhibited by malonyl Co-A (a product of the conversion of acetyl CoA -> fat in fat synthesis to prevent futile cycling)
  • Activated by glucagon through cAMP signalling to transport more fatty acyl-CoA into the mitochondria to be converted to energy.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the short and long term methods of controlling FA breakdown?

A 
-	Short-term control:
o	allosteric activation/inhibition 
o	malonyl CoA and glucagon
-	Long-term control:
o	changes in gene expression of 
o	CAT1/CPT1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the last step of FA breakdown?

A
  • The last step of FA break down is the actual removal of carbons from the long chain of the FA to give acetyl-CoA with each 2 carbons removed.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How many reactions are there in each cycle of beta oxidation of acyl-CoA? What happens with each cycle? What does unsaturated FA require?

A
  • A cycle of 4 reactions and with each cycle the FA loses 2 carbons in the form of one acetyl CoA molecule. (How many cycles of break down does palmitic acid, a 16-carbon fatty acid, undergo?)
  • Unsaturated FA require more enzymes.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which enzymes break down FA?

A
  • FA are broken down by a number of enzymes, mostly dehydrogenases (remove hydrogen)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which four reactions does each cycle of FA breakdown involve? What are the products? Where does beta oxidation occur?

A
  • Each cycle involves oxidation, hydrolysis, oxidation, thiolysis (“OHOT”)
    o In the process, 1 NADH and 1 FADH produced per cycle
  • Products of β-oxidation of a C-16 FA (palmitic acid):
    o ? acetyl Co-A – TCA cycle – 96 ATPs
    o ? NADH – TCA cycle – 21 ATPs
    o ? FADH - TCA cycle – 14 ATPs – ? total ATPs from 1 FA
  • B-oxidation of FA occurs in most tissues except brain and RBC.
    o FA oxidation cannot guarantee rapid enough ATP production in neurons of brain
    o No mitochondria in RBC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is lipogenesis?

A

Lipid Synthesis: Lipogenesis

- Process by which glucose is converted to FA to form fat.

17
Q

What two steps are involved in the process of lipogenesis?

A
  • Essentially a 2 step process:
    1. Glucose -> pyruvate -> TCA cycle -> citrate leaves cycle and mitochondrion
    2. Citrate in cytosol broken down by ATP-citrate lyase (ACLY) -> acetyl Co-A + HCO3 - + ATP (acetyl CoA carboxylase: ACCA) -> Malonyl CoA (2 carbon elongator) -> FA
18
Q

What determines the extension of the FA during lipogenesis?

Where does lipogenesis occur?

A
  • The formation of malonyl CoA determines the extension of the FA since each malonyl CoA formed is added to growing FA chain using enzyme fatty acid synthase.
  • Occurs mostly in liver, white adipose tissue and lactating mammary glands.
  • Essential (poly unsaturated) vs non-essential FA?
19
Q

How is lipogenesis regulated?

A
  • Main regulating step of lipogenesis is the conversion of acetyl CoA  malonyl CoA controlled by the enzyme:
    o acetyl CoA carboxylase (ACC)
  • Malonyl Co-A acts as an allosteric inhibitor of the Carnitine shuttle.
  • ACC is regulated in 3 ways:
  • Polymerization which occurs in the presence of citrate, depolymerization by palmitoyl CoA
  • Phosphorylation by cAMP-dependent kinases renders it inactive (glucagon) but insulin opposes phosphorylation and makes it active.
  • Gene/protein expression level (long term)
20
Q

What are ketone bodies? How are they different to fatty acids? Which organs can they be used by? Where are they synthesised?

A
  • Name given to 3 molecules produced during the break down of FA
  • Only difference is that they are water-soluble so easier to transport.
  • Can be used by a number of organs (including brain) to generate energy
  • Synthesized ONLY in the liver from acetyl CoA during ketogenesis
21
Q

Which ketone bodies can be formed from acetyl CoA during ketogenesis? Which steps then follow this? What stimulates this process?

A
  • Ketone bodies (acetoacetate and hydroxybutyrate) are produced from 3 acetyl CoA that join to form hydroxy-methyl-glutaryl-CoA.
  • HMG-CoA is then broken down to acetoacetate which can be converted to beta-hydroxybutyric acid or acetone.
  • Main limiting/regulatory step is the formation of HMG-CoA by HMG-CoA synthase
  • Synthesis of HMG-CoA synthase is stimulated by fasting, dietary fat, glucagon or insulin deficiency
22
Q

How and where can ketone bodies be used as energy?

A
  • Ketone bodies are used by many tissues (except liver) as a source of acetyl CoA which can be shuttled immediately into the TCA cycle.
    o Mostly used by brain and muscle under starvation; new born babies.
23
Q

What is a serious condition caused by ketone bodies?

A
  • A serious complication of diabetes is called ketoacidosis:
    o Untreated diabetes causes excessive high levels of ketone bodies which when released into the blood decrease the pH of the blood leading to an increase in acidity (acidosis).
    o Insulin inhibits important enzymes that stop ketogenesis: this is lost in diabetes
    o Acetoacetate and 3-hydroxybutyrate spontaneously form acetone when in excess – acetone breath
24
Q

What is ketoacidosis? What are its symptoms, triggers and treatment?

A
  • Leading cause of death in people under 24 with diabetes
  • Symptoms: bad breath (acetone), extreme thirst & urination, nausea, vomiting, lethargy, confusion, hyperventilation.
  • Triggers: low carb diet (body switches to lipolysis and ketogenesis for energy); missing a dose of insulin; infections, stress; alcohol; some medications; acute illness (anything that effects the body’s ability to use or produce insulin)
  • Treatment: IV fluids, replacement of electrolytes, IV insulin
25
Q

What can acetyl Co-A be produced from?

A 
-	Acetyl Co-A can be produced from:
o	Glucose
o	Fatty acids (B-oxidation)
o	Ketone bodies
o	Some amino acids
26
Q

What can Acetyl Co-A be transferred to?

A
  • Acetyl Co-A can be transferred to:
    o Fatty acids
    o Ketone bodies
    o TCA cycle
27
Q

What is end-product regulation of acetyl Co-A?

A

o Various pathways exist to prevent the over –production of acetyl Co-A

28
Q

What is metabolic flexibility? How can it be improved? What is metabolic inflexibility, when does it occur and what does it cause?

A
  • The ability to switch from glucose to fats as a source of energy as a response to the changes in metabolic demands (exercise vs fasting)
  • People who exercise regularly tend to have good metabolic flexibility
  • Metabolic inflexibility tends to occur in obese and diabetic people
    o Energy shift is impaired or slowed down resulting in inefficient energy consumption
    o Have decreased ability to burn fat
29
Q

Summarise fat metabolism.

A
  • Triglycerides are an essential source of energy
  • Broken down mostly in liver & muscle only in the presence of oxygen.
  • Lipolysis (break down of fats) is controlled by hormone-sensitive lipase through cAMP-kinase-phosphorylation and by adipose triglyceride lipase (ATGL) enzyme.
  • Fatty acids are then broken down to acetyl Co-A (β-oxidation) in mitochondria and controlled mainly through the Carnitine shuttle (regulation of carnitine palmitoyl transferase I [CPT] enzyme)
  • Spiral β-oxidation process generates acetyl Co-A + NADH and FADH2, occurs in most cells except brain + RBC
  • Lipogenesis occurs through intermediates such as malonyl Co-A and regulated mainly by enzyme acetyl Co-A carboxylase (ACC) through polymerisation, phosphorylation & gene expression.
  • Ketone bodies – important source of energy during exercise and starvation; formed from acetyl CoA and regulated by hydroxymethylglutaryl CoA synthase (HMG-CoA synthase).
  • Ketoacidosis – clinically relevant complication of diabetes.
  • Metabolic flexibility.

MET1 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions