Metabolic Pathways What is metabolism? Two major catabolic pathways: - glycolysis - citric acid cycle (and electron transport chain) One major anabolic mechanism: protein synthesis

What is Metabolism? n n Metabolism is the sum of all chemical reactions in the body. n n Chemical reactions can either create larger molecules (requires energy) or break down large molecules into smaller molecules (releases energy). n n The process of breaking down large molecules is called catabolism. n n The process of building larger molecules is called anabolism.

Catabolism n n Occurs in an orderly manner (not just random degradation) n n Breaks down large molecules into smaller molecules n n In the process, energy is released

Anabolism n n Occurs in an orderly manner n n Smaller molecules are used to build larger molecules n n This process requires energy n n The smaller molecules and energy are obtained from the catabolism of larger molecules (ie, food)

Catabolic and Anabolic Pathways Involve specific chemical reactions which occur in an orderly manner (not just random breaking or building of the molecule). - Each reaction is catalyzed by a specific enzyme. - Other compounds, besides those being metabolized, are required as intermediates in the reaction - Adenosine Triphosphate (ATP) - Nicotinamide adenine dinucleotide (NAD + ) - acetyl CoA

ATP n n ATP is the energy currency of the cell n n The structure of ATP is similar to that of nucleic acids n n The energy in ATP is “carried” in the phosphate groups - to convert ADP into ATP requires energy - the energy is stored as potential energy in the phosphate group bond - removal of the third phosphate releases that energy

NAD + n n NAD + can accept a hydrogen ion and become reduced to NADH: NAD + + H + ___ > NADH n n The added hydrogen ion can be carried to and used in other reactions in the body. n n Example: NAD + carries hydrogen ions to the enzymes in the electron transport chain of the mitochondria, where it plays a role in ATP production.

Acetyl CoA n n The enzyme coenzyme A converts acetyl groups (2-carbon structures) into acetyl CoA, which can then be used in catabolic reactions n n During the course of acetyl CoA production, energy is released and is used to convert NAD + to NADH

Glycolysis and the Citric Acid Cycle n n NOTE: Your book contains great detail in terms of the structures involved, the enzymes required at each step, and the places where ATP production occurs. DO NOT MEMORIZE THESE DETAILS! Instead, learn the following major features of the catabolic pathways.

Glycolysis n n Glycolysis is the breakdown of glucose into CO 2, H 2 O, and energy: C 6 H 12 O > 6 CO H 2 O + 38 ATP + heat n n Main point: the break down of glucose releases LOTS of energy: - about 40% in usable form (ATP) - about 60% as heat n n Two main steps are involved, occurring in the cytoplasm of cells (no organelles involved).

The two main steps of glycolysis n n First step: phosphorylation of glucose, and conversion of phosphorylated glucose to diphosphorylated fructose. - This step requires an “investment” of 2 ATP molecules - Once you have fructose 1,6-diphosphate, the second step can begin n n Second step: breakdown of fructose 1,6-diphosphate into 2 pyruvic acid molecules. - During these reactions, two NADH are formed - Four ATP molecules formed - Pyruvic acid used in aerobic or anaerobic metabolism

Instant Replay glucose glucose 6-phosphate fructose 1,6- diphosphate Step one: ATP Step two: fructose 1,6- diphosphate 2 ATP 2 NADH 2 pyruvic acid

What happens to pyruvic acid? n n In anaerobic respiration (oxygen absent): - pyruvic acid is converted to lactic acid - no further gain in ATP production occurs - lactic acid goes to the bloodstream, goes to the liver

What happens to pyruvic acid? n n In aerobic respiration (oxygen present): - pyruvic acid moves from cytoplasm to mitochondria - pyruvic acid (3 carbons) is converted to acetyl group (2 carbons), producing CO 2 in the process - CO 2 is produced from the food we eat, not from the O 2 we breath in! - This reaction is irreversible - acetyl group is converted to acetyl CoA by coenzyme A - acetyl CoA is used in the citric acid cycle.

Citric Acid Cycle n n Formerly called the Kreb’s cycle n n Acetyl CoA combines with oxaloacetic acid, forming citric acid n n A series of reactions then occurs resulting in: - one ATP produced - three NADH produced (goes to electron-transport chain) - two CO 2 molecules produced

Electron-transport Chain n n The main point: NADH carries H + ions to the electron- transport chain, resulting in production of ATP n n The H + ions are moved along the transport chain, eventually accumulating in the outer mitochondrial compartment n n The H + ions move back into the inner mitochondrial compartment via hydrogen channels, which are coupled to ATP production n n At the end of the transport chain, four hydrogen ions join with two oxygen molecules to form water: 4 H O > 2 H 2 O n n In the absence of oxygen, the transport chain stalls (no ATP production)

Catabolism of Fats and Proteins n n Fatty acids must be broken down and converted to acetyl CoA, which can then enter the citric acid cycle to generate ATP and NADH (which goes to the electron-transport chain) n n For amino acids, the amino groups are removed, and the remainder is broken down to acetyl CoA or pyruvic acid.

Anabolism: Protein Synthesis n n Recall that the amino acid sequence of proteins is determined by the nucleic acid base sequence of DNA. But how? n n Each amino acid is coded for by DNA codons - a codon is a triplet of bases (ie, CGA codes for alanine) - since there are four bases and 3 bases/codon, you could conceivably encode 64 amino acids (but you don’t!) - the code is degenerate; an amino acid can be encoded by more than one codon (ie; CGG also encodes alanine) - in addition, there are “start” and “stop” codons

Transcription of DNA into RNA n n DNA is transcribed into RNA - two strands of DNA separate - complementary RNA nucleotides pair with DNA - RNA nucleotides join to form single stranded mRNA - mRNA is processed to its final form (splicing) n n DNA also encodes other forms of RNA - ribosomal RNA (rRNA); forms ribosomes - transfer RNA (tRNA); carries amino acids to ribosome, recognizes mRNA codons

Translation of mRNA into protein n n The mRNA is translated into protein on ribosomes - ribosomes are composed of rRNA and protein, have two subunits - mRNA goes to a ribosome - tRNA has an anticodon, which can combine with complementary codon encoding a specific amino acid - the tRNA also carries the amino acid specified by its anticodon to the ribosome - the amino acids join each other (by peptide bonds) n n Proteins are then modified (shortened, glycocylated, assembled); called post-translational processing

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