Metabolic Pathways for Lipids and Amino Acids

Lipids fatty acids and glycerol Proteins amino acids

Gives us the nitrogen to synthesize nitrogen-containing compounds in our cells (new proteins and nucleic acids)

Both categories are further broken down in enzymatic reactions from there.

Adipocytes = fat cells that compose our adipose tissue These store triacylglycerols Body fat is our major source of stored energy

First step of dietary fat digestion: in the small intestine, fat globules mix with bile salts, and emulsification occurs.

Second step of dietary fat digestion: pancreatic lipases hydrolyze the triacylglycerols to yield monoacylglycerols and free fatty acids. These products get reabsorbed through the lining of the small

intestine and recombine once again to form triacylglycerols, then combine with proteins to form a lipoprotein called a chylomicron.

Where are all these internal organs, anyway?

Chylomicrons are transported through the bloodstream (now water soluble!) and can be carried whereever they are needed.

Used as energy when blood glucose is low and glycogen stores are depleted

Fat mobilization: triacylglycerols in the adipose tissue are broken down to fatty acids and glycerol

In the next sets of slides, we’ll learn how the glycerol and the fatty acids get processed once they’re broken apart

Activated by the hormones glucagon or epinephrine

Gets metabolized in the liver Glycerol is converted to dihydroxyacetone

phosphate in two steps, which we will not memorize, but this compound feeds into glycolysis and gluconeogenesis.

Yields a lot of energy! Metabolism of fatty acids: beta () oxidation, which

removes chunks of two carbons at a time. Each two carbon chunk is degraded into an acetyl-CoA unit,

which enters the citric acid cycle. And, the length of the fatty acid determines the number of

times the cycle repeats itself. For instance… myristic acid = 14 carbons = produces 7 acetyl-CoA

groups = goes through cycle 6 times

Beta oxidation: applies to saturated fatty acids with an even number of carbons. But many things we eat contain unsaturated fatty acids.

How are these processed? A cis fatty acid is turned into a trans fatty acid via an isomerase

Then, a hydration reaction adds water across the double bond.

Each cycle of beta oxidation yields one NADH, one FADH2, and one acetyl-CoA.

So, if you have a saturated fatty acid containing 16 carbons, what would be the NADH/FADH2 yield?

When we don’t have enough carbohydrates to meet our energy needs, the body will break down stored fats.

However, the breakdown of large amounts of fat will cause acetyl-CoA molecules to accumulate in the liver. These molecules will combine to form ketone bodies through the ketogenesis pathway. Ketone bodies, once produced in the liver, are then transported

to cells in the heart, brain, and skeletal muscle. Conversion back to acetyl-CoA generates small amounts of energy.

Sometimes ketone bodies are not completely metabolized – leading to ketosis – lowers pH of the blood, causes breathing difficulties.

Occurs when the body has met all of its energy needs and there is acetyl-CoA left over. In other words… a process a lot of us try to avoid, and a

process that has created a multi-billion dollar industry! Called lipogenesis

Overall: two carbon acetyl units are linked together to form palmitic acid (a 16-carbon fatty acid)

Longer or shorter fatty acids may be formed by either stopping the process short, or special enzymes that can continue the process longer

Takes place primarily in adipose tissue – site of formation and storage of triglycerides

When blood glucose is high, insulin moves glucose into the cells. Once inside the cell, insulin stimulates glycolysis and

pyruvate oxidation, which provides acetyl-CoA for synthesis of fatty acids

Why do proteins get digested? Provide amino acids for synthesis of new proteins in the

body Provide N atoms for synthesis of compounds such as

nucleotides Our major energy sources are carbohydrates and lipids, but

when they are not available, proteins can be used as an energy source

Stage 1: the stomach HCl released by glands creates an acidic environment (pH

2). Denatures proteins, activates enzymes that begin to hydrolyze peptide bonds

Stage 2: the small intestine Polypeptides from the stomach move into the small

intestine. Proteolytic enzymes (such as trypsin and chymotrypsin) complete the hydrolysis of the peptides into individual amino acids.

Then, the individual amino acids are absorbed through the intestinal walls into the bloodstream. From here, they get transported to the cells.

Or, proteins do not live forever in our bodies! Old proteins are constantly being replaced with new ones. The process of synthesizing proteins and breaking them

down = protein turnover For example, insulin has a half-life of 10 minutes, and

hemoglobin has a half-life of 120 days If a protein is damaged and/or ineffective, it is also

degraded and replaced The body cannot store nitrogen, so the excess gets

excreted as urea

It wouldn’t be the first choice. Normally, only about 10% of the body’s energy

needs is supplied by amino acids. However, under conditions of fasting or starvation,

when carbohydrate and fat stores are exhausted, amino acids are used as an energy source. If these conditions persist for a long time, breakdown of

body proteins can lead to a destruction of essential body tissues.

First, the amino group is removed, yielding a keto acid.

This keto acid can be converted into an intermediate which can feed into other metabolic pathways.

Most of the amino groups get converted to urea. Degradation of amino acids primarily occurs in the

liver.

What happens to all of the ammonium ions resulting from deamination of amino acids? The ammonium groups are toxic if they are allowed to

accumulate. A pathway called the urea cycle converts them to

urea, which is transported to the kidneys to form urine. In a typical day, an adult will excrete about 25-30 g of urea

in the urine – moreso if the diet is high in protein Occurs in the liver cells

The rest of the amino acid is sent into the citric acid cycle or another metabolic pathway. If the amino acid skeleton has 3 carbons, it can be

converted to pyruvate. If they have 4 or 5 carbons, they can be converted to

another intermediate in the citric acid cycle (oxaloacetate, or ketoglutarate).

Humans (unlike bacteria) can only synthesize 10 of the 20 naturally occurring amino acids. The ones that we can synthesize are called nonessential

amino acids The ones that we cannot synthesize – in other words, we

need to consume them – are called essential amino acids Some amino acids require merely a simple one-step

synthesis (a transamination); others require a multistep reaction. We will not memorize the steps for this class; just be aware that there are different pathways for the different amino acids.