Fatty acid catabolism -defects, ketones and regulation

Question 1

How do fatty acid catabolism defects come about?

Answer 1

Genetic defects in acyl CoA dehydrogenase (AD) (1st enzyme)

3 isoenzymes involved for different length carbon chains.

Question 2

Can acyl CoA dehydrogenase deficiency be treated?

Answer 2

Partially (low fat, high CHO diet) - leads to low energy, fat accumulation, vomiting, sleeplessness and even come can result from this deficiency. MCADD - most common

Question 3

How are fatty acid catabolism defects tested?

Answer 3

Heel prick screening - 3-5 days after birth.
Tested for 8 different inherited diseases.
MCADD

Question 4

How are ketones formed?

Answer 4

Acetyl CoA formed during fatty acid breakdown - forms this in stage 2 & 3 of catabolism (used to transfer metabolic energy)

Question 5

What makes up ketone bodies?

Answer 5

Acetone
Acetoacetate
D - Beta - hydroxybutyrate

Question 6

When does ketone body formation happen?

Answer 6

• carb unavailable ex: low carbohydrate

- starvation, fasting, untreated diabetes.

Question 7

Where is acetyl CoA from Beta- oxidation synthesised into ketone bodies?

Answer 7

In the liver.

Question 8

Which parts of ketone/reconverted acetyl co a are blood soluble and able to be exported to organs to conver to energy?

Answer 8

Acetoacetate, beta hydroxybutyrate. - acetyl coA makes these when it can’t join to anything
Produced ATP energy

Question 9

What promotes gluconeogenesis?

Answer 9

untreated diabetes, severely reduced food intake - slow the citric acid cycle as oxaloacetate used for essential glucose synthesis.

Question 10

When is the ketogenic diet useful?

Answer 10

To treat epilepsy.

Question 11

What does overproduction of ketone bodies do to the body?

Answer 11

Dangerous blood pH - lowers, acidosis - ketosis - coma

Question 12

How can ketosis be quantified?

Answer 12

By measuring the acidity of urine.

Sampling exhaled air for acetone via gas chromatography

Question 13

How is the regulation of fat catabolism measured?

Answer 13

The level of carnitine acyl-transferase-1 enzyme.

Question 14

What is AMP an indicator of?

Answer 14

Low energy.

Question 15

When is carnitine acyl-transferase -1 inhibited?

Answer 15

When fat breakdown at sufficient level for energy output and when fats start to be synthesised for fat synthesis and degradation will not happen at the same time.

Question 16

How is carnitine acyl-transferase-1 inhibited?

Answer 16

Allosterically by high concentrations of the first product in fatty acid synthesis = malonyl CoA blocks fatty acid import into mitochondria.

Question 17

What is the first product in fatty acid synthesis?

Answer 17

Malonyl CoA - it blocks fatty acid import into the mitochondria.

Question 18

What is another name for carnitine acyl-transferase-1?

Answer 18

Palmitate.

Question 19

What is AMP-kinase?

Answer 19

It is a key regulator.
When energy is low AMP/ATP ratio high = AMP kinase is turned on (phosphorylates and inactivated acetyl CoA carboxylase - which activated malonyl CoA) = UNBLOCKS

Question 20

How is fatty acid catabolism regulated?

Answer 20

• high energy indicators.
• high NADH/NAD = inhibits (dehydrogenase
• high acetyl coA - inhibits thiolase

Question 21

What do transcription factors do?

Answer 21

Up regulate transcription fat catabolism.

Question 22

What are 2 examples of transcription factors?

Answer 22

CREB - glucagon activated, turns on catabolism

PPAR - nuclear receptors, low energy, starvation