Ketogenesis

Question 0

What is the function of Ketogenesis?

Answer 0

• there are limitations to the metabolism of NEFA. The NEFA are toxic to membranes at concentration above 2mM- thus places limitation on how much fat can be utilised.
• to allow more fat to be utilised in times of need the liver has pathway called KETOGENESIS which can metabolise Anefa to ketone bodies
• ketone bodies are water soluble and readily utilised by many aerobic tissues (muscle, kidney, and brain but only in humans) and so is a less toxic form of fat.
• The overall effect is to allow more fat to be mobilised and more glucose to be spared

Question 1

What are ketone bodies?

Answer 1

Simply chemicals that occur free in solution in the body fluids. 2 major ketone bodies
1. Butyric acid
2. Acetoacetic
These are acids that are soluble and easily transported into tissues.
-there are also 2 minor compounds derived by spontaneous non enzymic decarboxylation of these ketone bodies.
A) isopropanol
B)acetone -hence in animals with elevated levels of ketone you can smell acetone breath

They are primarily in the liver, carried in the blood free in solution and utilised by several anaerobic tissues.

Question 2

What is the location of ketogenesis?

Answer 2

Liver, mitochondrial matrix

-the rumen wall (of ruminants) can also synthesis butyric acid

Question 3

The pathway of ketogenesis- apparently is discussed in the lecture

Answer 3

Better find it and learn it homie G

Question 4

Regulation of ketogenesis?

Answer 4

Substrate supply is the major feature I’d the supply of acetylCoA within the mitochondria of the liver. Major factors:
A) high rates of fat mobilisation (the ultimate substrate) ie factors controlling the balance between lipolysis and esterification in adipose tissue
B) high activity of CPT1- allows fat to enter mitochondria for B oxidation to produce acetylCoA. b oxidation produces NADH/ FADH that allows rapid ATP production and inhibition of the TCA cycle - therefore more acetyleCoA goes to ketogenesis.

C) the interacting factor is a relative shortage if glucose for the tissues. This could be a high demand, low supply or and endocrine fault (diabetes). Whatever the reason it causes exaggerated endocrine changes which impact on the fat mobilisation.

Question 5

What are the special features of ketone body formation?

Answer 5

The key feature is 2 levels if ketone body formation
1) physiological ketosis- controlled and useful
2) pathological ketosis- uncontrolled and damaging
Look at page 48

Question 6

What is the definition of the below: 
Ketone bodies 
Ketogenesis 
Ketosis 
Ketanaemia
Ketonuria
A-keto-acids

Answer 6

Ketone bodies: butyric acid or acetoacetate
Ketogenesis: the pathway
Ketosis: the syndrome associated with elevated blood levels of ketone bodies
Ketanaemia: elevated ketone bodies in the blood
Ketonuria: ketone bodies can be detected in the urine
A-keto-acids

Question 7

Ketone body utilisation:

What enzymes are the key requirments?

Answer 7

Acetoacetate, succinylCoA transferase (called CoA transferase for short) is the key enzyme requirement:
Butyrate + NAD➡ Acetoacetate + NADH

SuccinylyCoA + Acetoacetate ➡ (CoA transferase)➡ AcetoacetylCoA + succinate

AcetoacetylCoA + CoA➡ 2acetylCoA

Many aerobic tissues can utilise ketone bodies ie muscle, gut, kidneys. These tissues will preferentially utilise ketone bodies when available and thus spare blood glucose for those tissues with an absolute glucose requirement.
The nervous system of MOST animals CANNOT utilise ketone bodies, except the human brain