Metabolism II

• Nearly all of the energy needed by the human body is provided by the oxidation of carbohydrates and lipids. Whereas carbohydrates provide a readily available source of energy, lipids function primarily as an energy reserve.

• It is interesting to compare the relative amounts of energy provided by various biochemicals in a typical 154 lb male. The free glucose in the blood provides only a 40 kcal energy reserve -- only enough to maintain body functions for a few minutes.

• Glycogen remaining stored in the liver and muscles after an overnight fast, amounts to about 600 kcal energy. Glycogen reserves can maintain body functions for about one day without new inputs of food. Protein (mostly in muscle) contains a substantial energy reserve of about 25,000 kcal.

• Finally, lipid reserves containing 100,000 kcal of energy can maintain human body functions without food for 30-40 days with sufficient water. Lipids or fats represent about 24 pounds of the body weight in a 154 pound male.

Lipid Metabolism

• Lipolysis – breakdown of lipids for entry into TCA cycle

• Triglycerides are predominant lipid in body used for energy

• Stored in adipose tissue• Glycerol backbone & 3 fatty acidsThe first step in lipid metabolism is the hydrolysis

of the lipid in the cytoplasm to produce glycerol and fatty acids.

Glycerol• Has a 3 carbon backbone that fatty acids attach to• it is metabolized quite readily into an intermediate in

glycolysis, dihydroxyacetone phosphate, which may be converted into pyruvic acid

• dihydroxyacetone may also be used in gluconeogenesis to make glucose-6-phosphate for glucose to the blood or glycogen depending upon what is required at that time.

Fatty Acids• Chain of hydrocarbons• Can be saturated or unsaturated• Fatty acids are oxidized to acetyl CoA in

the mitochondria using the fatty acid spiral.

Fatty Acid Spiral

• One turn of the fatty acid spiral produces ATP from the interaction of the coenzymes FAD (step 1) and NAD+ (step 3) with the electron transport chain. Total ATP per turn of the fatty acid spiral is:

• Step 1 - FAD into e.t.c. = 2 ATPStep 3 - NAD+ into e.t.c. = 3 ATP Total ATP per turn of spiral = 5 ATP

• In order to calculate total ATP from the fatty acid spiral, you must calculate the number of turns that the spiral makes. Remember that the number of turns is found by subtracting one from the number of acetyl CoA produced.

• Example with Palmitic Acid = 16 carbons = 8 acetyl groups

• Number of turns of fatty acid spiral = 8-1 = 7 turns

• ATP from fatty acid spiral = 7 turns and 5 per turn = 35 ATP. [activation energy = 1 ATP] NET ATP from Fatty Acid Spiral = 35 - 1 = 34 ATP

Beta Oxidation• The acetyl CoA produced from the fatty

acid spiral enters the TCA cycle. When calculating ATP production, you have to show how many acetyl CoA are produced from a given fatty acid as this controls how many "turns" the citric acid cycle makes.

• Used palmitic acid (16 carbons) The fatty acid spiral ends with the production of 8 acetyl CoA

• 1 ATP, 3 NADH, & 1 FADH2 = 12 ATP per acetyl CoA in TCA cycle

• All NADH & FADH2 will enter Electron Transport system

 Step ATP produced

One acetyl CoA per turn C.A.C.

+12 ATP

8 Acetyl CoA = 8 turns C.A.C.

8 x 12 = 96 ATP

Fatty Acid Spiral 34 ATP

GRAND TOTAL  130 ATP

• These events occur in liver and muscle. During sustained exercise the cells of slow twitch muscle fibers (which possess mitochondria) utilize ß-oxidation as the major source of ATP.

Protein Metabolism

• Proteins make up the structural tissue for muscles and tendons, transport oxygen or hemoglobin, catalyze all biochemical reactions as enzymes, and regulate reactions as hormones. Our bodies must be able to synthesize the many proteins, amino acids, and other non-protein nitrogen containing compounds needed for growth, replacement, and repair. Proteins in excess are used to supply energy or build reserves of glucose, glycogen, or lipids.

nitrogen or amino acid pool

• mixture of amino acids available in the cell derived from dietary sources or the degradation of protein. Since proteins and amino acids are not stored in the body, there is a constant turnover of protein. Some protein is constantly being synthesized while other protein is being degraded

Synthesis of New Amino Acids

• these reactions can also be used to synthesize amino acids needed or not present in the diet. An amino acid may be synthesized if there is an available "root" ketoacid with a synthetic connection to the final amino acid. Since an appropriate "root" keto acid does not exist for eight amino acids, (lys, leu, ile, met, thr, try, val, phe), they are essential and must be included in the diet because they cannot be synthesized

• if there are excess proteins in the diet those amino acids converted into pyruvic acid and acetyl CoA can be converted into lipids by the lipogenesis process. If carbohydrates are lacking in the diet or if glucose cannot get into the cells (as in diabetes), then those amino acids converted into pyruvic acid and oxaloacetic acids can be converted into glucose or glycogen.

• The hormones cortisone and cortisol from the adrenal cortex stimulate the synthesis of glucose from amino acids in the liver and also function as antagonists to insulin.

oxidative deamination

• Deamination is also an oxidative reaction that occurs under aerobic conditions in all tissues but especially the liver. During oxidative deamination, an amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia and the amine functional group is replaced by the ketone group. The ammonia eventually goes into the urea cycle.