CHAPTER 24

1. Metabolic Pathways for Lipids and Amino Acids CHAPTER 24

2. 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. How do we digest things that aren’t carbs?

3. 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. A. Digestion of Triacylglycerols

5. Where are all these internal organs, anyway?

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

7. 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 Mobilization of fat stores

8. 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. Metabolism of Glycerol

9. Yields a lot of energy! • Metabolism of fatty acids: beta (b) 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 B. Oxidation of fatty acids

10. 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. Unsaturated Fatty Acids: What’s the Difference?

11. 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? C. ATP and Fatty Acid Oxidation

12. 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. D. Ketogenesis and Ketone Bodies

13. 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 E. Fatty Acid Synthesis

14. 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 Regulation of Fatty Acid Synthesis

15. 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 F. Digestion of Proteins

16. 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. Process of Protein Digestion

17. 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 Protein Turnover

18. 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. Does Our Body Obtain Energy from Amino Acids?

19. First, the a-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. G. Degradation of Amino Acids

20. 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 H. Urea Cycle

21. 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 a-ketoglutarate). J. Fates of the Carbon Atoms from Amino Acids

22. 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. K. Synthesis of Amino Acids