Fasting/Fed states

Question 1

What is the primary source of energy (and the hormone associated) of the body in the fed state? Are there exceptions?

Answer 1

Primary source in a fed state is glucose, which requires the presence of Insulin. Insulin is only secreted if it detects high levels of glucose, and the brain, liver, RBC’s, muscle and fat all use glucose as the primary source of energy in fed state. EXCEPTION: Heart, which needs fatty acids due to higher energy conc. It however prefers Ketones (made only in between meals) as its PRIMARY source of energy.

Question 2

What is the calorie production of sugar, fat, protein and alcohol?

Answer 2

Sugar and protein both produce 4 kcal of energy, whereas fat produces 9 kcal. Alcohol produces 7 kcal of energy however only the liver can use it.

Question 3

In the fed state, what is the molecule the body is all trying to produce and how does it get there?

Answer 3

The point is to produce Acetyl CoA. Sugars and carbs go through glycolysis to make pyruvate, and pyruvate turns to Acetyl CoA via Pyruvate DH. Fats make Acetyl CoA via Beta oxidation. Proteins get broken down (often to pyruvate and then PDH to acetyl CoA).

Question 4

What is the consequence of having high ATP?

Answer 4

High ATP shuts down the ETC, resulting in high NADH and FADH2, which in turn shuts down leading to high Acetyl CoA, high pyruvate and high glucose. Hepatocytes at this point is going to shift to energy storage mode.

Question 5

What is “glycogen” and what are the 2 things that must be present in order to make glycogen?

Answer 5

Glycogen is composed of sugar molecules being connected together both horizontally and vertically (branches). In order to produce glycogen, insulin must be present (which is only present in the fed state) and the hepatocytes must detect high levels of ATP.

Question 6

What are the 2 organs that make glycogen and how do they differ?

Answer 6

Liver and Muscles can both produce glycogen. However, the muscles can only store glycogen to use the it for itself, whereas the liver can store glycogen but also ship it out for the use of other tissues.

Question 7

What is a “fatty acid?”

Answer 7

Long chains of Acetyl CoA linked together horizontally (no branches) made by the liver.

Question 8

How does a fat differ from a fatty acid?

Answer 8

A fat is 3 fatty acids held together by glycerol, aka Triacylglycerols, TAGs.

Question 9

How does fatty acids and glycerol differ in the liver in terms of storage?

Answer 9

Fatty acids are converted to TAGs and exported out of the liver, but glycogen is stored in the liver.

Question 10

What is the fate of excess acetyl CoA in the liver?

Answer 10

It can be converted to fatty acids to be shipped out, or it can be converted to cholesterol.

Question 11

How are TAG’s shipped out of the liver, what protein is necessary to do this?

Answer 11

Since TAGs are lipids and therefore not soluble in the blood, it requires apolipoprotein B100 to convert TAGs into VLDLs, which gets shipped out in the blood.

Question 12

What is the fate of cholesterol?

Answer 12

Some of it goes with the VLDL as cholesterol esters, but most gets converted into bile salts, stored in the gall bladder and released into the bile in order to emulsify fats.

Question 13

What are the 2 sources of TAGs?

Answer 13

From excess sugars in the liver as VLDL’s, and from our diet in the gut as Chylomicrons.

Question 14

What is the apolipoprotein necessary to make chylomicrons?

Answer 14

B48, found in the gut.

Question 15

What enzyme turns the TAGs to glycerol and what is the fate of glycerol? Where do the TAG’s go?

Answer 15

TAG’s from the VLDL’s and Chylomicrons gets dumped into adipose tissue, and the TAG’s are converted back to fatty acids and glycerol is released, via the enzyme LIPOPROTEIN LIPASE (LPL). The glycerol gets reabsorbed into the liver.

Question 16

What induces the enzyme LPL to break down TAGs into fatty acids (stored in the adipocytes) and glycerol (released into the blood and back into the liver?)

Answer 16

Induced by insulin.

Question 17

How does adipose tissues uptake glucose and why is it important for adipose tissues to uptake glucose?

Answer 17

Energy storage requires energy input and the only time adipocytes will store energy as fat is when it has enough ATP (thus enough glucose uptake to perform ETC and make ATP). Glucose uptake in the adipocytes need GLUT-4, which is induced by insulin.

Question 18

What is the intermediate in adipose tissues between glucose and TAGs?

Answer 18

It requires the intermediate glycerol P. Only time Glycerol P will be made from glucose is if the adipocytes have enough energy of its own to divert the glucose from the ETC to making glycerol P.

Question 19

What is the serum lipid count in a diabetic and why?

Answer 19

Diabetics will have hyperlipidemia because insulin in required for uptake of glucose into adipocytes (via GLUT-4), and the adipocytes need enough ATP for itself before it can divert the glucose from making ATP to storing fat. No insulin = no uptake of glucose by adipose tissues = no storage of fat = increased accumulation of VLDLs and chylomicrons in the blood = hyperlipidemia.

Question 20

In the fasting state, what are the predominant hormones?

Answer 20

Glucagon and “stress hormones” which includes cortisol, epi, GH.

Question 21

What is “substrate level phosphorylation?”

Answer 21

Basically glycolysis, which DOES NOT REQUIRE O2 in order to make ATP.

Question 22

In the fasting state, what is the primary source of Acetyl CoA among all body tissues and what are exceptions?

Answer 22

Instead of glucose, the primary source of acetyl CoA which is then converted to energy via ETC in the fasting state is TAGs. RBC’s cannot do ETC, it can only do glycolysis so it can only use glucose, and the brain also the brain (although under emergency conditions the brain can use other sources of energy).

Question 23

What feeds the brain and the RBCs (two tissues that use glucose regardless of feeding or fasting) at times of fasting?

Answer 23

The liver, via breaking down glycogen (glycogenlysis, however glycogen stores are limited) and more importantly, via gluconeogenesis.

Question 24

Regardless of feeding or fasting what is the energy levels of the liver and how?

Answer 24

Liver is always high in ATP in feeding (via using glucose) and high in fasting (via burning fats). This is necessary because the liver is always active in both feeding and fasting states.

Question 25

What is important about the enzyme pyruvate DH in terms of when it works and the direction it works?

Answer 25

Pyruvate can turn to acetyl CoA, but not vice versa, so PDH can only go one-way and is irreversible. Further, it only works under the influence of insulin.

Question 26

If fats cannot be used to turn back into glucose (why?) how can we re-make glucose in the body?

Answer 26

PDH is irreversible and only works in presence of insulin, so acetyl CoA cannot be converted back to pyruvate, pyruvate needs to come from other sources. Other sources include protein breakdown (primarily Alanine) and lactate breakdown.

Question 27

What is the main protein that can be broken down to pyruvate for the purposes of making glucose? What enzyme is necessary?

Answer 27

Alanine is the main amino acid that is used to convert to pyruvate, via the enzyme ALT (alanine transaminase) and this requires vit B6.

Question 28

Why does lactate never build up in the body (barring liver injury?)

Answer 28

The Cori cycle always converts lactate back into glucose in the liver, unless there is liver injury.

Question 29

What is the organ that creates Ketones and what are ketones composed of?

Answer 29

Ketones are made in the liver, composed of acetyl CoA.

Question 30

What is the fate of increased acetyl CoA in the liver?

Answer 30

The liver can turn the Acetyl CoA into a fat and ship it out via VLDLs, or it can produce Ketone Bodies from the acetyl CoA. Of course, to do either the liver must first ensure it has high enough ATP for its own use, so the conversion of acetyl CoA to fats or ketones occur only to excess Acetyl CoA.

Question 31

What is the point of Ketones?

Answer 31

It is the primary source of energy of muscles, particularly the Heart. Also the Kidneys use ketones.

Question 32

In the fed state, basically what is the body trying to do?

Answer 32

This is the insulin world, so in the fed state glycogen and fat is being made.

Question 33

In the fasting state, what is the body trying to do?

Answer 33

Fasting state is the world of glucagon, and thus glycogenlysis, gluconeogenesis (both used to make glucose) and ketones are being produced.