Metabolism Chapter 25

An Introduction to Cellular Metabolism Figure 25–1

Essential Nutrients 45 – 50 molecules must be ingested. This includes representatives from the 4 major organic molecule groups, plus a number of inorganic substances such as including water, vitamins and minerals (Na, Fe, etc.) The USDA has made major revision in its nutritional recommendations. http://www.health.gov/dietaryguidelines/dga2005/document/

It was never based on solid science

Nutrient – A substance in food used by the body for growth, maintenance, energy and repair. USDA IOM for young adult female Carbohydrates: 271g (55%) 130g (45 - 65%) Lipid: total 65g (17%) 20 – 25% saturated 17g (7.8%) Protein: 91g (18%) 56g (10 – 35%) Water: 1500 ml (average) per day.

Uses of nutrients Carbohydrate: Primary energy molecule. Also found on cell membranes and as part of structure of connective tissue matrix molecules Lipid: Energy storage, plasma membrane structure, cushioning, steroid hormones. Proteins: Enzymes, receptors, hormones, structures of all kinds. Must be “complete” or “complimentary” in order to supply essential amino acids.

Nutrient Use in Cellular Metabolism

Essential amino acids

10 Essential Amino Acids 8 not synthesized: isoleucine, leucine, lysine, threonine, tryptophan, phenylalanine, valine, and methionine 2 insufficiently synthesized: arginine and histidine

4 Types of Nitrogen Compounds Amino acids: framework of all proteins, glycoproteins, and lipoproteins Purines and pyrimidines: nitrogenous bases of RNA and DNA

4 Types of Nitrogen Compounds Creatine: energy storage in muscle (creatine phosphate) Porphyrins: bind metal ions essential to hemoglobin, myoglobin, and cytochromes

Energy Metabolism Metabolism = catabolism + anabolism Cellular respiration is a series of catabolic reactions that provide energy for the production of This energy is used to generate ATP from phosphorylation of ADP. It is a series of Redox reactions. ATP

Energy Metabolism: Generation of ATP

Overview of aerobic respiration

Summary of steps of energy metabolism

Generation of ATP by “substrate-level phosphorylation”

Oxidative phosphorylation

Overview of cellular respiration

Carbohydrate Metabolism Oxidation of Glucose C6H12O6 + 6 O2 6 CO2 + 6 H2O + 36 ATP + Heat

Glycolysis It is the first stage in cellular respiration

Steps of glycolysis

Aerobic vs anaerobic pathways

Overview of TCA (Krebs cycle)

TCA (Krebs) Cycle

Summary: The TCA Cycle CH3CO — CoA + 3NAD + FAD + GDP + Pi + 2 H2O  CoA + 2 CO2 + 3NADH + FADH2 + 2 H+ + GTP

The ETS creates an chemiosmotic gradient

The Electron Transport System

The ETS

Summary of ATP synthesis Gains & losses

Visual summary of cellular respiration

Carbohydrate Breakdown and Synthesis Figure 25–7

Glycogenesis/ Glycogenolysis

Gluconeogenesis Is the synthesis of glucose from noncarbohydrate precursors: lactic acid glycerol amino acids Stores glucose as glycogen in liver and skeletal muscle

Summary of metabolic pathways

Lipid metabolism: oxidation

3 Energy Benefits of Beta-Oxidation For each 2-carbon fragment removed from fatty acid, cell gains: 12 ATP from acetyl-CoA in TCA cycle 5 ATP from NADH Cell can gain 144 ATP molecules from breakdown of one 18-carbon fatty acid molecule Fatty acid breakdown yields about 1.5 times the energy of glucose breakdown

Lipid Transport and Utilization Figure 25–9

5 Classes of Lipoproteins Chylomicrons Very low-density lipoproteins (VLDLs) Intermediate-density lipoproteins (IDLs) Low-density lipoproteins (LDLs) High-density lipoproteins (HDLs)

Chylomicrons Are produced in intestinal tract Are too large to diffuse across capillary wall Enter lymphatic capillaries Travel through thoracic duct: to venous circulation and systemic arteries

Distribution of Other Lipoproteins: Step 1 Liver cells synthesize VLDLs: for discharge into bloodstream

Distribution of Other Lipoproteins: Step 2 Lipoprotein lipase removes many triglycerides from VLDLs: leaving IDLs Triglycerides are broken down: into fatty acids and monoglycerides

Distribution of Other Lipoproteins: Step 3 When IDLs reach liver: additional triglycerides are removed protein content of lipoprotein is altered LDLs are created LDLs are transported to peripheral tissues to deliver cholesterol

Distribution of Other Lipoproteins: Step 4 LDLs leave bloodstream through capillary pores: or cross endothelium by vesicular transport

Distribution of Other Lipoproteins: Step 5 In peripheral tissues: LDLs are absorbed through receptor-mediated endocytosis Amino acids and cholesterol enter the cytoplasm

Distribution of Other Lipoproteins: Step 6 & 7 Cholesterol not used by the cell: diffuses out of cell Cholesterol reenters bloodstream: is absorbed by HDLs and returned to liver

Distribution of Other Lipoproteins: Step 8 In the liver: HDLs are absorbed cholesterol is extracted Recovered cholesterol is used: in synthesis of LDLs in excreted in bile salts

Distribution of Other Lipoproteins: Step 9 Free HDLs are released into bloodstream: travel into peripheral tissues absorb additional cholesterol

Composition of Lipoproteins

Proteins The body synthesizes 100,000 to 140,000 proteins: each with different form, function, and structure All proteins are built from the 20 amino acids

Amino Acid Catabolism Figure 25–10 (Navigator)

Amination Figure 25–11

Amino acid use in TCA cycle

Protein metabolism in the Liver

Summary: Pathways of Catabolism and Anabolism Figure 25–12

5 Metabolic Tissues Each tissue has its own requirements Liver Adipose tissue Skeletal muscle Neural tissue Other peripheral tissues

Other Peripheral Tissues Do not maintain large metabolic reserves Can metabolize glucose, fatty acids, and other substrates Preferred energy source varies: according to instructions from endocrine system

Metabolic Interactions Relationships among 5 components change over 24-hour period Body has 2 patterns of daily metabolic activity: absorptive state postabsorptive state

Regulatory Hormones: Effects on Peripheral Metabolism Table 25–1

Pathways of the Absorptive state

The effects of insulin on metabolism

The Postabsorptive state

Influences of Glucagon on blood glucose levels

Lipid and Amino Acid Catabolism Generates acetyl-CoA Increased concentration of acetyl-CoA: causes ketone bodies to form

Ketone Bodies Acetoacetate Acetone Betahydroxybutyrate

Ketone Bodies Liver cells do not catabolize ketone bodies: compounds diffuse into general circulation peripheral cells absorb ketone bodies Cells reconvert ketone bodies to acetyl-CoA for TCA cycle

Ketone Bodies Are acids that dissociate in solution Fasting produces ketosis: a high concentration of ketone bodies in body fluids

Ketonemia Is the appearance of ketone bodies in bloodstream Lowers plasma pH, which must be controlled by buffers

Ketoacidosis Is a dangerous drop in blood pH: caused by high ketone levels exceeding buffering capacities

Severe Ketoacidosis Circulating concentration of ketone bodies can reach 200 mg dl: pH may fall below 7.05 may cause coma, cardiac arrhythmias, death

Minerals and Vitamins Are essential components of the diet The body does not synthesize minerals Cells synthesize only small quantities of few vitamins

Minerals and Mineral Reserves Table 25–3

Minerals Are inorganic ions released through dissociation of electrolytes

Importance of Minerals Ions such as sodium, chloride and potassium determine osmotic concentrations of body fluids Ions are essential: cofactors in many enzymatic reactions in many important physiological processes

Metals Each component of ETS requires an iron atom Final cytochrome of ETS requires a copper ion

Mineral Reserves The body contains significant mineral reserves: that help reduce effects of variations in diet

The Fat-Soluble Vitamins Table 25–4

Fat-Soluble Vitamins Vitamins A, D, E, and K: are absorbed primarily from the digestive tract along with lipids of micelles normally diffuse into cell membranes and lipids in liver and adipose tissue

Vitamin A Vitamin D Vitamin E A structural component of visual pigment retinal Vitamin D Is converted to calcitriol: which increases rate of intestinal calcium and phosphorus absorption Vitamin E Stabilizes intracellular membranes

Vitamin K Helps synthesize several proteins: including 3 clotting factors

Vitamin Reserves The body contains significant reserves of fat-soluble vitamins Normal metabolism can continue several months without dietary sources

The Water-Soluble Vitamins Table 25–5

Metabolic Rate If daily energy intake exceeds energy demands: body stores excess energy as triglycerides in adipose tissue If daily caloric expenditures exceeds dietary supply: body uses energy reserves, loses weight

Cholecystokinin (CCK): Adrenocorticotropic hormone (ACTH): Leptin: Hormonal Effects Thyroxine: controls overall metabolism T4 assay measures thyroxine in blood Cholecystokinin (CCK): suppresses appetite Adrenocorticotropic hormone (ACTH): Leptin: released by adipose tissues during absorptive state binds to CNS neurons that suppress appetite

Heat Balance

Regulatory pathways for homeostatic control of body temperature

Temperature regulation mechanisms

Maynard or Hans?