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USMLE Biochemistry > Fatty acids > Flashcards

Fatty acids Flashcards

1
Q

What 2 molecules make up a triglyceride?

A
  • 3 Fatty acids

- Glycerol

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2
Q

What are most lipids taken up as in the intestine?

A

Degraded to free fatty acids in intestine

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3
Q

What do enterocytes convert fatty acids to?

A

Triacylglycerol (triglycerides)

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4
Q

In what form are lipids carried through the plasma

A

As chylomicrons

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5
Q

What structure/fluid carried the chylomicrons away from the intestine?

A

The lymph in the lacteal

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6
Q

Once the triglycerides reach their target tissue what are the converted back into and by what enzyme?

A

Converted back to free fatty acids by lipoprotein lipase

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7
Q

Where can lipoprotein lipase be found?

A
  • Endothelial surface of capillaries

- Abundant in adipocytes and muscle tissue

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8
Q

What does saturated fat refer to?

A

Contains no double bonds

  • ‘Saturated’ w. hydrogen
  • Solid at room temo
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9
Q

What is an unsaturated fat?

A

Fat / fatty acid contains at least one double bound

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10
Q

What is a polyunsaturated and monounsturated fat?

A
  • Monounsaturated: One double bond

- Polyunsaturated: More than one double bond

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11
Q

What does trans and cis fats refer to?

What fats are good and bad?

A

The location of the double bond in an unsaturated fat

  • Trans fats have double bonds on both sides of the molecule -> making them straight
  • Cis fats have double bonds only on one side
  • Trans can increase LDL, lower HDL
  • Omega 3 (double bond, 3 carbons from omega end), can lower triglyceride levels
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12
Q

Through what process are trans fats created?

A

Partial hydrogenation (food processing method)

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13
Q

What are fatty acids synthesised from?

A
  • Liver
  • Mammary glands
  • Adipose tissue
  • Excess carbs and proteins -> fatty acids
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14
Q

Where are fatty acids stored and in what form?

A
  • Adipose tissue

- Stored as triglycerides

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15
Q

Through what process are fatty acids broken down into Acetyl CoA?

A

Beta-oxidation

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16
Q

What molecule are fatty acids broken down into to then yield ATP?

A

Acetyl CoA

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17
Q

How does a ‘fed’ individual get a high citrate level?

A

Lots of acetyl-CoA -> TCA cycle -> build up of ATP

  • ATP inhibits isocitrate dehydrogenase (rate limiting step of TCA cycle)
  • Citrate then builds up as TCA cycle has slowed down
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18
Q

What does a high citrate levels indicate?

A

Indicates high levels of excess energy in the cell

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19
Q

What enzyme combines acetyl-CoA and oxaloacetate to make citrate?

A

Citrate synthase

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20
Q

What molecule can cross the mitochondrial membrane acetyl coA or citrate?

A

Citrate - via the citrate shuttle

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21
Q

How does citrate block glycolysis?

A

Inhibits PFK1

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22
Q

Describe how citrate is converted to Acetyl-CoA

What are the other substrates?

What enzyme?

A

Citrate -> Acetyl CoA

CoA -> Oxaloacetate
ATP -> ADP

Enzyme: ATP-Citrate Lyase

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23
Q

What is the rate limiting step of fatty acid synthesis?

A

Acetyl coA -> Malonyl-CoA

CO2 -> (adds carbon)

Enzyme: Acetyl-CoA Carboxylase

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24
Q

What is the rate-limiting enzyme of fatty acid synthesis?

A

Acetyl-CoA carboxylase

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25
What is the cofactor for acetyk-CoA Carboxylase?
Biotin
26
What substances increase the activity of Acetyl-CoA carboxylase?
- Citrate | - Insulin
27
What substances decrease the activity of Acetyl-CoA carboxylase?
- Glucagon | - Epinephrine
28
What does Malonyl-coA inhibit?
B-oxidation
29
What does biotin act as a cofactor for?
Caboxylation enzymes - Adds 1-carbon groups via CO2 - Pyruvate carboxylase (gluconeogenesis) - Acetyl-CoA carboxylase (fatty acid synthesis) - Propionyl-CoA carboxylase
30
What is Palmitate a result of combining?
- Acetyl CoA | - Malonyl CoA
31
How many carbons are in palmitate?
16
32
What enzyme converts Acetyl CoA and Malonyl CoA into Palmitate?
Fatty acid synthase (final step of fatty acid synthesis)
33
What does Fatty acid synthase require to convert Acetyl CoA and Malonyl CoA into Palmitate?
NADPH (from HMP shunt)
34
What are fatty acids stored as?`
Triacylglycerols in adipose tissue
35
What is the key enzyme in fatty acid breakdown?
Hormone sensitive lipase
36
What is hormone sensitive lipase activated by?
- Glucagon | - Epinephrine
37
What does Hormone sensitive lipase do?
Removes fatty acids from TAG in adipocytes
38
What intermediate of glycolysis/gluconeogenesis can Glycerol be converted into in the liver?
Dihydroxyacetone Phosphate
39
What is Glycerol first converted into before Dihydroxyacetone Phosphate?
Glycerol-3-Phosphate (via Glycerol Kinase)
40
What enzyme converts Glycerol into Glycerol-3-Phosphate?
Glycerol Kinase
41
What enzyme converts Glycerol-3-Phosphate into Dihydroxyacetone phosphate?
Glycerol-3-Phosphate Dehydrogenase
42
What are fatty acids transported via?
Albumin | - Glycerol is soluble so can freely transport
43
What tissues do not use fatty acids as energy?
- RBCs (glycolysis only, no mitochondria) | - Brain (glucose and ketones only)
44
What does B-oxidation produce from fatty acids?
- Acetyl CoA - NADH - FADH2
45
What does the first step of Beta-oxidation involve?
Fatty acid being converted to fatty acyl CoA by: - Long chain fatty acyl CoA synthetase - CoA added - ATP -> ADP
46
What does the second step od B-oxidation involve?
Transport of fatty acyl coA to the inner mitochondria
47
How is fatty acyl coA transported to the inner mitochondria?
Carnitine shuttle
48
How can you get carnitine?
Diet From lysine and methionine - Liver and kidney denovo - Muscle and heart depened on diet or other tissues
49
How is fatty acyl CoA transported to the mitochondrial matrix?
Can pass into inner membrane space - Converted here to Acyl Carnitine by Carnitine Palmitoyl Transferase-1 (requires carnitine) - Acyl Carnitine can travel through inner membrane - CPT-2 enzyme with CoA can convert Acyl Carnitine into Fatty acyl CoA
50
What does Carnitine Palmitoyl Transferase-1 do?
Replaces the CoA on Fatty Acyl CoA with Carnitine to make Acyl Carnitine
51
Where is Carnitine Palmitoyl Transferase-1 found?
On the outer membrane of the mitochondria | - Molecules in cytosol can effect it
52
What inhibits Carnitine Palmitoyl Transferase-1?
Malonyl-CoA
53
What enzyme converts Acyl Carnitine in the mitochondrial matrix into Fatty Acyl CoA?
CPT-2 (with CoA)
54
What can cause carntine deficiency?
- Malnutrition - Liver disease - Increased requirements (trauma, burns, pregnancy) - Hemodialysis (decreased synthesis; loss through membranes)
55
What does carnitine deficiency result in?
- Inability to transport LCFA to mitochondria - Accumulation of LCFA in cells - Low serum carnitine and acylcarnitine levels
56
What are the symtpoms/signs of carnitine deficiency?
- Muscle weakness, esp during exercise - Cardiomyopathy - Hypoketotic hypoglycemia when fasting, tissues overuse glucose, poor ketone synthesis w/o fatty acid breakdown
57
What is primary systemic carnitine deficiency a mutation in?
- Mutation affecting carnitine uptake into cells
58
What are the signs symptoms of primary systemic carnitine deficiency?
Infantile phenotype presents in first two years of life - Encephalopathy - Hepatomegaly - Hyperammonia (liver dysfunction) - Hypoketoic hypoglycemia - Low serum carnitine, kidneys cannot resorb it - Reduced carnitine levels in muscle, liver, heart (biopsies) All due to build-up of fatty acids which cannot be metabolised
59
What does Beta oxidation involve? What does it generate?
Removal of 2 carbons in each beta oxidation cycle - Shortens chain - Generates NADH, FADH2, Acetyl CoA
60
What is the enzyme in the first step of B-oxidation?
Acyl-CoA dehydrogenase - Adds double bond between alpha and B carbon - B carbon is oxidised - alpha carbon and acetyl coA broken off - Genrates an FADH2
61
What are the 4 acyl-CoA Dehydrogenases?
- Short - Medium - Long - Very long
62
What acyl-CoA Dehydrogenase is most commonly deficient?
Medium chain Aceyl-CoA dehydrogenase (MCAD)
63
What are the specific signs of MCAD deficiency? why do you get these signs?
- Poor oxidation of 6-10 carbon fatty acids - Dicarboxylic acids 6-10 carbons in urine - High acylcarnitine levels (as build up) - Severe hypoglycemia w/o ketones - Gluconeogenesis shut-down as pyruvate carboxylase requires acetyl oA which is low in absnce of B-oxidation
64
How is MCAD deficiency inherited?
Aut Recessive
65
How is MCAD deficiency exacerbated?
Fasting/infection | - Treatment is to avoid fasting
66
What are odd chain fatty acids broken down into by B-oxidation (acyl-CoA Dehydrogenase)?
Propionyl-CoA (cannot be broken down further)
67
What is propionyl coA then converted into if it cannot be fully broken down by B-oxidation (acyl-CoA Dehydrogenase)?
Converted to Succinyl-CoA
68
What enzyme breaks down propionyl-CoA into Succinyl-CoA?
Propionyl-CoA Carboxylase (biotin cofactor)
69
Can odd or even FA be converted to glucose?
Only odd chain
70
What is proprionyl coA first converted into before Succinyl-CoA?
MethylMalonyl-CoA (biotin required)
71
What reaction requires B12?
MethylMalonyl-CoA to Succinyl-CoA
72
What can be converted to Proprionyl coA?
Amino acids Cholesterol Odd chain fatty acids
73
What is methylmalonic acidemia due to a deficiency in?
Deficiency in Methylmalonyl-CoA mutase Converts: - MMCoA -> Succinyl CoA
74
What are the signs/symptoms of Methylmalonic acidemia?
- Anion gap acidosis - CNS dysfunction - Often fatal in early life
75
How are Methylmalonyl-CoA and Succinyl-CoA similar?
Isomers of each other

USMLE Biochemistry (44 decks)

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