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 FADH 2, and one acetyl-CoA.  So, if you have a saturated fatty acid containing 16 carbons, what would be the NADH/FADH 2 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 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.