Metabolism Basics Title - metabolism basics

Two faces of metabolism Catabolism - degradation Anabolism - biosynthesis There are two faces to metabolism - breakdown (degradation) and synthesis

Catabolism Catabolic sequences yield energy Oxidative ATP, NADH Catabolic sequences yield energy. The oxidation of NADH to NAD+ is catalyzed by the electron transport chain and the synthesis of ATP is catalyzed in the process of oxidative phosphorylation (oxphos).

Catabolic Pathways ATP, NADH Glycolysis GTP, NADH, FADH2 NADPH ATP ATP, NADPH Glycolysis TCA (Krebs) cycle -oxidation of fatty acids Oxidation of -keto acids (from amino acids) Hexose monophosphate path Oxidative phosphorylation Photophosphorylation Examples of catabolic pathways with the compounds produced.

Catabolism is Convergent The Krebs citric acid cycles collects and completely oxidizes the acetyls from carbohydrate, fat and protein catabolism. The electron transport chain and oxphos regenerate the coenzymes and make ATP. The oxygen is utilized in the process - not produced as intimated in the figure.

Catabolic Regulation Allosteric Covalent Hormonal Altered gene expression ATP and PFK-1 Phosphorylation of glycogen phosphorylase Epinephrine  [cAMP] Protein phosphorylation AA oxidizing enzymes Metabolic process are regulated by various means - examples are listed.

Localization of Catabolism Mitochondria (matrix, membrane) -oxidation AA oxidation Pyruvate oxidation Oxidative phosphorylation Catabolism may occur in specific sites within the cell. The mitochodria does lots of oxidations.

Localization of Catabolism Cytosol Glycolysis Hexose-P Chloroplast Photophosphorylation Other compartments are also involved.

Compartmentation of Catabolism With two compartments there must be separate pools and there is exchange between tem catalyzed by carriers.

Tissue Specialization in Catabolism Glycolysis Krebs Cycle Fatty acid oxidation Urea cycle -keto acid oxidation Every Cell Almost every cell (not RBC) Most tissues (not brain) Liver Liver (except branched chains) Certain tissues carry out specialized catabolic reactions.

Irreversibility of Catabolism The breakdown is irreversible. Energy in the form of ATP is a product.

Summary: Catabolism Oxidative Convergent Tightly regulated Localized intracellularly Separate pools Tissue-specific Universal “Irreversible” Exergonic The key facts of catabolism.

Anabolism (Biosynthesis) Reductive Cofactor: usually NADPH Pentose-P pathway Glutamate dehydrogenase Photosynthetic electron transfer NADH + NADP+ NAD+ + NADPH The other side of the coin is biosynthesis (anabolism). Reducing power and energy usually required.

Anabolism: Divergent There are standard simple precursors with divergent pathways leading to specific products.

Anabolism: Regulation Anabolism is also regulated. Glutamine goes to several different products.

Anabolism: Localization in Cells Gluconeogenesis Fatty acid synthesis Glycogen synthesis Starch synthesis Amino acid synthesis Cytosol (mainly) Cytosol (Chloroplasts) Chloroplast Anabolism is also localized. Distinct pools: In mitos: [NAD+]/[NADH] high In cytosol: [NADPH]/[NADP+] high

Anabolism: Tissue-Specific Gluconeogenesis Fatty acid synthesis Steroid hormones Glycogen synthesis Vitamins Liver (kidney) Liver, mammary gland Adrenal cortex, ovaries, testes Muscle, liver No tissue; thus required in diet Anabolism is also tissue-specific.

Anabolism: “Irreversible” Anabolism is also irreversible. Thus catabolism and anabolism are like a pair of one-way streets.

Two Separate Pathways Catabolic path  Anabolic path Two separate pathways - at least for a few reactions.

Reciprocal Regulation Anabolic and catabolic pathways are reciprocally regulated Regulation occurs at reactions unique to the path Same regulator has opposite effect on path Epinephrine Stimulates -oxidation Inhibits fatty acid synthesis The regulation occurs doubly - activation of one pathway and inhibition of the other and visa versa.

Summary: Anabolism Reductive (NADPH) Divergent Regulated Localized At branch points Reciprocally with catabolism Localized Generally in the cytosol Anabolism facts

Summary: Anabolism Tissue-specific Liver “Irreversible” Use of ATP Separate path from catabolism More facts