WEEK3: OVERVIEW OF POST ABSORPTIVE STATE AND METABOLISM Flashcards

1
Q

What is post absorptive state?

Outline the events that happen in post absorptive state.

A

When there is no food left in the gut after digestion,the body enters the post absorptive state.

If this continues and no more food is taken in the body goes into fasting.

Commonly this happens overnight, between the evening meal and breakfast.

The overnight fast is often the only time when most people go into the fasted state.

If fasting continues, the body will eventually move from long-term fasting into starvation.

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2
Q

When does insulin secretion stop, at what glucose concentration?
State the functions of glucagon during onset of fasting.

A

*The post absorptive state the blood glucose level falls from the fed state level- 7mM towards the level reached in the fasted state- 3mM

*Blood glucose concentration falls below 5mM secretion of insulin from the b- cells of the Islets of Langerhans of the pancreas stops.

*As the concentration drops further, the hormone glucagon, is secreted from the a- cells of the Islets of Langerhans of the pancreas.

*Glucagon is a peptide hormone which mobilize food reserves from stores, to replace glucose which is no longer being taken up from the intestine.

*Glucagon stimulates the breakdown of liver glycogen (but not muscle glycogen) releasing glucose into the blood

*It breaks down triacyl glycerol in adipose tissue, producing fatty acid, which is released into the blood, forming an alternative source of metabolic energy to glucose in many tissues

*Glucagon also stimulates synthesis of key gluconeogenic enzymes in the cytoplasm of liver cells.

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3
Q

What is the major food reserve in the body?

Name the hormone which hydrolyze the ester bond linking each fatty acid to glycerol.

Describe how TAG is broken down.

What happens to the fatty acids released?

Outline hormones that can activate hormone sensitive lipase.

A

1.The major food reserve in the body is triacyl glycerol (TAG)

  1. hormone sensitive lipase.

Exist in inactive form but can be activated when the adipocyte is stimulated by hormones.

3.
*Hormone sensitive lipase releases a fatty acid from TAG, leaving a diacyl glycerol.

*This is then hydrolyzed first by a diacyl glycerol lipase, then by a monoacylglycerol lipase, releasing the remaining two fatty acids.

4.
*The fatty acid released is not soluble in the blood and can only leave the cell by binding to plasma albumin forming a fatty acid – albumin complex

Hormone sensitive lipase is activated by a number of hormones including:

*Glucagon, adrenaline (epinephrine), thyroid stimulating hormone (TSH), and adrenal corticotropic hormone (ACTH)

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4
Q

State Blood Concentrations of Glucose and Fatty acids in different metabolic states.

Fed state
Normal
Fasted state

A

GLUCOSE

FED= 7-8
NORMAL= 5
FASTED =3

FATS
FED=0.2
NORMAL=0.4
FASTED 1.2

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5
Q

How many fatty acids molecules are carried per albumin?

What is the maximal fatty acid concentration in blood?

A

1.Each albumin molecule has two high affinity binding sites for fatty acid, so will normally carry a maximum of two fatty acid molecules per albumin

This limits the blood concentration of fatty acid to a maximum of about 1.2 – 1.4 mM, and it normally does not exceed this.

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6
Q

How and Where are Fatty Acids Used?

Name the substance which acyl CoA is transformed into to get through the inner mitochondrial membrane.

A
  1. Fatty acids are taken up into cells and converted to acyl CoA form immediately inside the cell.
    They are transported to the mitochondria in this form but get through the inner mitochondrial membrane by transferring to a carrier molecule, carnitine.

Acyl carnitine crosses the inner membrane into the matrix where the carnitine again exchanges with CoA to form acyl CoA.

Acyl CoA is broken down by the b-oxidation pathway, which splits off successive two carbon units in the form of acetyl CoA. NADH and FADH2 are formed in the process.

The acetyl CoA formed readily feeds into the Krebs’ cycle where it is oxidized to two molecules of CO2.
More NADH and FADH2 are formed in this process.

Thus, fatty acids can be readily broken down in the mitochondria to generate energy in the form of ATP.

However, all the carbons of the molecule are converted to CO2. There is no mechanism for salvage of carbons from acetyl CoA, which cannot therefore be used for synthesis.

Any cell containing sufficient mitochondria can get its energy from fatty acid, provided that the fatty acids can get into the mitochondria quickly enough.

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7
Q

Which cells are not able to use fatty acids in fasted state?
Why?

A

1.Red blood cells
*They do not have mitochondria.

2.Nervous tissue of the brain and spinal cord
*This is because fatty acids cannot get into the cells fast enough, their uptake is impeded by the blood-brain barrier.

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8
Q

Describe the BBB.

A

*Its anatomical basis is probably the unusually tight connections between the endothelial cells lining the capillaries of the CNS

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9
Q

What is gluconeogenesis?

A

This is a metabolic pathway which synthesizes glucose from non-carbohydrate substrates.

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10
Q

State the non-carbohydrate substances which can be used in gluconeogenesis.

A

Amino acids
Glycerol
Lactate
Pyruvate

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11
Q

NOTE: Gluconeogenesis is the reverse of Glycolysis.
Describe the process of Gluconeogenesis.

A
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12
Q

State the 2 major tissues that carry out gluconeogenesis.

A

The major gluconeogenic tissues are liver and kidneys.

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13
Q

The first thing to clarify is that fatty acids cannot be used as a substrate.
Why is that the case?

A

The reason for this is that all carbons from fatty acids are converted to acetyl CoA, and acetyl CoA is completely broken down in Krebs’ cycle to CO2.

Thus, no carbons from fatty acid are available to be used for biosynthesis.

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14
Q

State the 3 ketones produced during starvation.

Which tissue uses ketones mostly?

How are the ketones used to release energy?

A

There are two main ones – acetoacetate, and b-hydroxybutyrate, though small amounts of acetone are also present (and sometimes makes the breath of fasting individuals smell)

Brain, skeletal muscles.

Ketones are readily oxidized by many tissues, especially muscles.

When they are present in the blood, they are the preferred metabolite for energy production.

They are oxidized in the mitochondrial matrix, where they are converted to acetyl CoA which then enters Krebs’ cycle.

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