Chapter 5 - Cell Respiration and Metabolism Metabolism - the sum of all the chemical reactions that occur in the body. It is comprised of:  anabolism – synthesis of molecules, requires input of energy  catabolism – break down of molecules, releases energy

We have been designed to liberate energy from food molecules by aerobic cellular respiration. This process is described as aerobic because oxygen is required. Why is oxygen required? Oxygen is the final e- acceptor. Aerobic cellular respiration occurs in four stages: glycolysis transition reaction Krebs cycle (citric acid cycle) electron transport pathway

C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O + ATP

WARNING: What follows is a simplified and condensed version of cellular respiration and is only appropriate for this class.

Glycolysis – glucose must be “activated” by the addition of two phosphate groups P. The addition of the P also traps glucose within the cell. 2ADP + P i 2ATP C 6 H 12 O 6 2 C 3 H 4 O 3 glucose pyruvic acid 2NAD + 4H 2NADH 2

AMP + P ADP + P i ATP This reaction is reversible. High energy energy bonds hold the P. When NAD is reduced, a pair of hydrogen atoms donates a pair of e-, one of which then binds one proton and the other proton follows along = NADH + H +. We simplify this with NADH 2.

If oxygen is not present to take the e- from NADH 2, then the e- will be donated to pyruvic acid = Lactic acid pathway (anaerobic respiration) The final product is lactic acid. This meta- bolic pathway only yields 2 ATP/ molecule.

Cells cannot store very much glucose because the glucose affects the cell’s osmolarity (see ch. 6). The glucose is converted to glycogen (or fatty acids) for storage = glycogenesis. glucose glu–6–P glu– 1—P glycogen [glu + glu + glu + glu + … glycogen]

The stored glycogen can be converted to glucose for use by the cell or secreted into the bloodstream (this only in the liver) = glycogenolysis. [glycogen glu + glu + glu + glu + …] glycogen glu–1–P glu– 6—P liver enzymes glucose

Only liver cells contain glucose – 6 – phosphatase, which removes P from glu – 6—P and liberates free glucose. The free glucose is then transported out of the cell into the blood stream.

Gluconeogenesis = liver cells contain another enzyme, lactic acid dehydrogenase, which converts lactic acid to pyruvic acid. The pyruvic acid is then converted to glu – 6—P (this is the reverse of glycolysis). The glu – 6—P can then be used to make glycogen or released as free glucose. The production of glucose from noncarbohydrate molecules, e.g. lactic acid, amino acids, fatty acids, is gluconeogenesis. (The Cori cycle is the production of glu from lactic acid.)

Continuation of Aerobic Respiration Transition reaction = pyruvic acid moves into the matrix of the mitochondrion. CO 2 is cleaved off and at the same time Coenzyme A is added.Coenzyme A is derived from the vitamin pantotenic acid. NAD + 2H NADH 2 2C 3 H 4 O 3 + 2CoA 2C 2 H 3 O-CoA + 2CO 2 pyruvic acid coenzyme A acetyl-CoA carbon dioxide

Krebs Cycle Acetic acid (2C) is added to oxaloacetic acid (4C) to form citric acid (6C). CO 2 is enzymatically removed. 3NAD+6H 3NADH 2 2C 2 H 3 O-CoA 4CO 2 FAD+2H FADH 2 2ADP+P i 2ATP

Electron Transport System e- are passed along a chain of molecules to O 2, which acts as the final e- acceptor. max 30 ADP+P i 30 ADP 2 H + + 2e- + ½ O 2 H 2 O

If the last cytochrome remained in a reduced state, it would be unable to accept more e-. E- transport would then progress only to the next-to-last cytochrome. This process would continue until all of the elements of the chain remained in the reduced state. At this point, the system would stop and no ATP could be produced in the mitochondrion. With the system incapacitated, NADH 2 and FADH 2 could not become oxidized by donating their electrons to the chain and, through inhibition of Krebs cycle enzymes, no more NADH 2 and FADH 2 could be produced in the mitochondrion. The Krebs cycle would stop and respiration would become anaerobic.

Lipids and proteins can also be used in aerobic respiration. Some organs preferentially use molecules other than glucose. Why were we designed this way? To prevent depletion of glucose and conserve it for the brain. We can store only small amounts of ATP. If food molecules are still available and ATP concentration continues to rise, glycolysis is inhibited and glucose is converted into glycogen and fats instead = glycogenesis and lipogenesis

Lipogenesis Excess glucose does not complete respiration but instead is converted into glycerol and fatty acids. The acetyl-CoA subunits from the transition reaction are added together to produce fatty acids. This occurs primarily in adipose tissue and the liver.

Lipolysis Triglycerides are hydrolyzed into glycerol and free fatty acids (FFA) by lipolysis. In some tissues glycerol can be converted into phosphoglyceraldehyde. FFAs are a major energy source and are metabolized by  -oxidation.

Amino Acids Excess amino acids (a.a.) in the diet are not simply stored as additional protein – instead they are deaminated and the carbon skeleton is either respired or converted to carbohydrates or fats. Adequate amounts of amino acids are required for growth and repair. Some a.a. can be make by rearranging parts of carbohydrates and essential a.a. A new amino acid can be obtained by transamination. –Amine group (NH 2 ) transferred from one amino acid to form another amino acid and a keto acid. –Catalyzed by a specific enzyme (transaminase).

Excess amino acids are processed for excretion by oxidative deamination. The amine group is removed and converted to urea, which is then excreted by the kidneys.

Not all cells can use glucose as the energy source. Blood contains a variety of energy sources: –Glucose and ketone bodies, fatty acids, lactic acid, and amino acids. Different tissues preferentially use different energy molecules. –Blood [glucose] maintained as many organs spare glucose. Why?