Class 25 metabolism

Metabolism

What is Lipogenesis

• The process of making and storing fat when the body has more energy than it needs right away

• occurs mainly in adipose tissue and in the liver

1st step of Lipogenesis

extra glucose from food goes through glycolysis to make pyruvate

2nd step of Lipogenesis

pyruvate moves into mitochondria and is converted into acetyl-CoA

3rd step of lipogenesis

When the cell already has plenty of energy, that acetyl coA is redirected. instead of going through the citric acid cycle (to make atp), it leaves the mitochondria and is used in the cytoplasm to build fatty acids 

4th step of lipogenesis

These fatty acids are then combined with glycerol to form triglycerides which are stored for later use

1st step in fatty acid and triglyceride synthesis

1. make acetyl-CoA (the building block)

• glucose is broken down through glycolysis into pyruvate, which enters mitochondria and is converted into acetyl-CoA

2nd step in fatty acid and triglyceride synthesis

2. Make Malonyl- CoA (the carbon donor of fatty acids) 

• The enzyme acetyl coA carboxylase adds one carbon to acetylene coA, forming malonyl coa, which has three carbons  

• Malonyl coa is the immediate source of the two carbon untis used to elongate the fatty acid chain  

3rd step in fatty acid and triglyceride synthesis

3. Build fatty acids  

• The enzyme fatty acid synthase is a large multi enzyme complex in the cytoplasm  

• It constructs the fatty acid chain 

• It repeatedly links together two carbon units from malonyl coA 

• After several rounds of elongation the product is typically palmitate, a fatty acid that is 16 carbons long  

4th step of fatty acid and triglyceride synthesis

4. Assemble triglycerides  

• Newly formed fatty acids combine with glycerol to form triglycerides 

• These are then packaged and stored in adipocytes (fat cells) for future energy use  

Lipogenesis is the process of converting excess ______ into _____ for storage

glucose, fat

What molecule is the starting building block for fatty acid synthesis

Acetyl-CoA

The enzyme that converts acetyl-CoA to malonyl-CoA is

___acetyl-CoA carboxylase .

What is the role of fatty acid synthase? 

builds fatty acid chains from malonyl-CoA

What is Palmitate?

a fatty acid that is 16 carbons longs

newly formed _______ combine with glycerol to form triglycerides

fatty acids

What is Lipolysis?

the break down of fat for energy, becomes active when body needs extra fuel.

1st step of lipolysis

• Triglyceride breakdown

• In adipocytes, the enzyme hormone sensitive lipase (HSL) cuts stored triglycerides into free acids and glycerol  

2nd step of lipolysis

• Fatty acid mobilization

• the free fatty acids travel through the bloodstream to other tissues such as muscle and liver   

3rd step of lipolysis

• Beta Oxidation (energy extraction)

• inside target cells fatty acids enter the mitochondria  

  - here they are broken down by beta oxidation  

  - this process removes two carbon units from the fatty acid to produce acetyl- CoA 

  - each cycle of beta oxidation also produces NADH and FADH2

4th step of lipolysis

• atp production

- the acetyl coa produced then enters the citric acid cycle (krebs cycle) and then oxidative phosphorylation which produces ATP.  

Lipolysis is the process of breaking down______ into ______and ______

triglycerides, fatty acids, glycerol

When is lipolysis most active?

during fasting or exercise

Which enzyme is responsible for breaking down triglycerides in adipose tissue?

Hormone sensitive lipase (HSL)

fatty acids released from adipose tissue travel to ____________ and ____________ to be used for energy.

muscle and liver

what process breaks fatty acids into acetyl-CoA

Beta oxidation

what happens to acetyl CoA after it is produced from fatty acids

enters the citric acid cycle to produce atp

what is a product of lipolysis

fatty acids

during prolonged exercise why does lipolysis increase

To provide an alternative energy source (fat) when glucose is limited

lipolysis allows the body to _____ when glucose is low

use fat for energy / generate ATP from fat

what are ketone bodies

• molecules made by the liver when glucose levels are low

• the liver takes the acetyl-CoA produced from the beta oxidation of fatty acids and uses it to form the two main ketone bodies: Acetoacetate and β-hydroxybutyrate

what happens to ketone bodies once they are produced?

• released into bloodstream and transported to tissues

• primarily to brain, heart, and skeletal muscle

• in these tissues ketone bodies are converted back to acetyl-CoA which then enters the citric acid cycle to generate atp

What is ketogenesis?

Ketone body production

1st step of Ketogenesis

• formation of acetoacetyl-CoA

• two Acetyl-CoA molecules combine to form

  Acetoacetyl-CoA

2nd step of ketogenesis

• formation of HMG-CoA

• Acetoacetyl-CoA combines with another Acetyl-

  CoA to make HMG-CoA

3rd step of ketogenesis

Production of Acetoacetate:

 HMG-CoA is cleaved to release Acetoacetate

 This is the first ketone body

4th step of ketogenesis

4. Formation of Beta-Hydroxybutyrate

 Acetoacetate is reduced and forms β-

hydroxybutyrate

 This is the second ketone body

Ketone Body Breakdown for Energy

In target tissues, the ketones (acetoacetate and beta-hydroxybutyrate) are converted to Acetyl CoA, which can enter the Citric Acid Cycle and be used to generate ATP.

1. Acetoacetate is converted into acetoacetyl-CoA

 This step uses the enzyme thiophorase.

2. Acetoacetyl-CoA is split into two acetyl-CoA molecules

1. Beta-hydroxybutyrate can also feed into this pathway

 Beta-hydroxybutyrate is first converted into acetoacetate.

2. Acetoacetate is converted into acetoacetyl-CoA

 This step uses the enzyme thiophorase

3. Acetoacetyl-CoA is split into two acetyl-CoA molecules

Why are ketone bodies made by the liver

Through beta-oxidation, fatty acids are converted into acetyl-CoA. Under normal conditions, this acetyl-CoA would enter the citric acid cycle to produce ATP. However, during fasting, the liver is prioritizing gluconeogenesis.

What does the liver do when glucose is scarce?

1. makes new glucose through gluconeogenesis

2. breaks down stored fat (triglycerides → fatty acids → beta-oxidation)

Both gluconeogenesis and the citric acid require what?

oxaloacetate (OAA)

where does OAA go during fasting

OAA is diverted toward gluconeogenesis to make glucose.

this leaves insufficient OAA for the citric acid cycle

As a result, acetyl-CoA cannot enter the cycle and is instead converted into ketone bodies.

what happens to ketone bodies

The ketone bodies are released from the liver into the bloodstream and transported to tissues such as thebrain, heart, and skeletal muscle.

In these tissues OAA is available (they are not performing gluconeogenesis).

The ketone bodies are therefore converted back into acetyl-CoA and the Acetyl-CoA enters the citric acid cycle to produce ATP.

During fasting, fatty acids are broken down through __________________________ to produce

__________________________.

Beta-oxidation → Acetyl-CoA

During fasting, oxaloacetate (OAA) in the liver is primarily used for what?

gluconeogenesis

Why is Acetyl CoA diverted to ketone body production in the liver?

Not enough oxaloacetate (OAA) available for the citric acid cycle

what are the two ketone bodies?

Acetoacetate; β-hydroxybutyrate

In other tissues, ketone bodies are converted back into __________________________.

acetyl-CoA

Why is OAA available in other tissues but not in the liver during fasting?

They are not performing gluconeogenesis, so OAA is available

Both carbohydrates and fats are ultimately broken down into __________________________.

acetyl-CoA

In protein metabolism proteins are broken down into

individual amino acids, which are then broken down into carbon skeletons and ammonia

proteins metabolism is tightly linked to what

carbohydrate metabolism, since the two share many of the same molecules and energy pathways

Deamination

• the key reaction in amino acid breakdown

• which removes the amino group (–NH₂) from

  the amino acid.

• This process occurs primarily in the liver and produces ammonia (NH₃) and a corresponding keto acid. The keto acid can then enter various metabolic pathways, while the toxic ammonia is converted to urea for safe excretion through urine.

After deamination, the remaining keto acid can enter several metabolic pathways (remember each amino acid forms its own unique keto acid):

• a keto acid may be funneled into the citric acid cycle to produce atp

• another may serve as the starting point for gluconeogenesis to form glucose

• another may be converted to acetly-coa and lead to the production of ketone bodies

Fed (absorptive) state

• lasts for about four hours after a meal

• blood levels of glucose, amino acids, and fatty acids rise

• pancreas releases insulin

Fasted (Post absorptive) state

• blood glucose starts to fall

• pancreas releases glucagon

• breaks down glycogen, fat and sometimes protein to keep supplying energy

Carbohydrate Metabolism in the Fed State

• carbs are broken into glucose, which enters the bloodstream

• Insulin helps move glucose into muscle and fat cells and encourages liver and muscles to store it as glycogen

Glycogenesis

• making glycogen from glucose

• part of carb metabolism in fed state

Glycolysis

• Breaking glucose down to make atp

• part of carb metabolism in the fed state

Carbohydrate Metabolism in the fasted state

• insulin decreases and glucagon increases

• liver becomes main source of glucose through glycogenolysis and gluconeogenesis

• muscle tissues uses its own glycogen for energy but doesn’t release glucose into the blood bc it lacks the enzyme glucose 6 phosphate

Fat Metabolism in fed state

• dietary fats are absorbed and reassembled into triglycerides

• the triglycerides are then packaged into chylomicrons for transport in the blood

• insulin promotes lipogenesis (making triglycerides/fat storage)

Glycogenolysis

• breaking glycogen back into glucose

• part of carb metabolism in fasted state

Gluconeogenesis

• making new glucose from amino acids and glycerol

• part of carb metabolism in fasted state

fat metabolism in fasted state

• low insulin and high glucagon, fat metabolism shifts

• Lipolysis: fat stores in adipose tissue are broken down into fatty acids and glycerol

• beta oxidation: fatty acids travel to the liver and muscles and are converted into acetyl-CoA

• Ketogenesis: in prolonged fasting, liver converts fatty acids into ketone bodies, which serve as an alternative source of acetyl CoA

Protein metabolism in fed state

amino acids from dietary protein are used for

protein synthesis: building new proteins for growth and repair

minor energy use: a small portion may be broken down for energy

insulin encourages cells to take up amino acids, promotes protein synthesis, and inhibits protein breakdown

Protein metabolism in the fasted state

• when glucose and fat are limited the body turns to protein

• Proteolysis: muscle proteins are broken down into amino acids

• Gluconeogenesis: some amino acids are converted into glucose

• energy use: the carbon skeletons of amino acids can be oxidized to make atp

• prolonged fasting can cause muscle wasting as more protein is broken down to maintain blood glucose

Anabolism

builds complex molecules (like proteins and fats) and uses energy

Catabolism

breaks large molecules down into smaller ones and releases energy

Insulins role in hormone regulation

• made by the beta cells of the pancreas and released after eating

• when blood glucose rises it the body’s main anabolic (building) hormone

• Carbohydrates: Insulin helps cells take in glucose and promotes glycogenesis (storing glucose as glycogen in the liver and muscles).

• • Fats: Insulin stimulates fat storage (lipogenesis) and prevents fat breakdown (lipolysis).

• Proteins: Insulin promotes amino acid uptake and protein synthesis, while preventing protein breakdown.

Glucagons role in hormone regulation

• made by the alpha cells of the pancreas

• released when blood glucose levels drop

• Carbohydrates: Stimulates breaking glycogen into glucose (glycogenolysis) and making new glucose (gluconeogenesis).

• Fats: Promotes fat breakdown (lipolysis).

• Proteins: Encourage protein breakdown (proteolysis) in the liver to supply amino acids for glucose production.

Cortisol

• the stress hormone

• released during stress or when blood sugar is low

• Carbohydrates: Increases glucose production (gluconeogenesis) in the liver and makes tissues

  less sensitive to insulin; this keeps glucose available for the brain.

  • Fats: Stimulate fat breakdown (lipolysis).

  • Proteins: Increases protein breakdown in muscle (proteolysis), providing amino acids for

  gluconeogenesis.

  In Summary: Cortisol is mainly catabolic. It breaks down stored nutrients to provide energy

  during stress.

Growth Hormone

Growth hormone (GH) is produced by the pituitary gland and supports growth, repair, and metabolism.

• Carbohydrates: Decrease glucose uptake by cells, helping maintain blood glucose.

• Fats: Increases fat breakdown (lipolysis).

• Proteins: Stimulates protein synthesis and reduces protein breakdown.

In Summary: GH is anabolic for proteins (builds tissue) but catabolic for fats and carbs (uses

them for fuel).

Thyroid Hormones

The thyroid gland produces thyroxine (T₄) and triiodothyronine (T₃), which control how fast metabolism

runs.

• Carbohydrates: Increase glucose absorption and stimulate both glycogen breakdown

(glycogenolysis) and glucose production (gluconeogenesis).

• Fats: Increase fat breakdown (lipolysis) and fatty acid oxidation.

• Proteins: Stimulate both protein synthesis and breakdown; yes, you read that right – it can do

both; overall, it increases overall protein turnover

In Summary: Thyroid hormones act like a metabolic accelerator, speeding up both anabolic

and catabolic reactions.