METABOLISM

Metabolism

1. Metabolism – all chemical reactions necessary to maintain life

2. Catabolism – breakdown from complex to simple

3. Anabolism – synthetic reaction; from simple to complex

4. Oxidation – the gain of oxygen or loss of hydrogen; loss of energy (electron)

5. Reduction – the gain of hydrogen or loss of oxygen; gain of energy (electron)

6. Redox – whenever one compound is reduced, another is oxidized

7. Coenzymes – temporary hydrogen (or electron) acceptor

-a. NAD⁺ (nicotinamide adenine dinucleotide) – from niacin

-b. FAD (flavin adenine dinucleotide) – from riboflavin, B₂

8. ATP synthesis – captured energy

-a. Substrate level phosphorylation –phosphate from phosphorylated substrate

-b. Oxidative phosphorylation – H⁺ pass through ATPase channels; gradient energy

-c. Chemiosmotic process – food energy (chem) push H+ across membrane (osmotic)

Carbohydrate Metabolism

1. Glucose – all carbohydrates are broken down to; taken up by body cells

2. Glucose-6-phosphate – 1 ATP -ADP; trapped in all but liver, kidney, intestine cell

3. Glucose oxidation – cellular respiration; ATP production

-a. C₆H₁₂0₆ + 6O₂→6H₂O + 6CO₂ + 36 ATP + heat

4. Glycogen metabolism – glycogenesis and glycogenolysis

5. Gluconeogenesis – convert glycerol and amino acids to glycogen

Glucose oxidation: glycolysis

1. Sugar activation – energy investment phase

-a. Glucose – 2 ATP to 2 ADP: add phosphate on

-b. Fructose-1,6-diphosphate – the end product of sugar activation

2. Sugar cleavage – fructose-1,6-diphosphate cleaved; 2 3 carbon isomers

-a. Dihydroxyacetone phosphate – one isomer; converts to other isomer

-b. Glyceraldehyde phosphate – other isomer; convert to other isomer

3. Oxidation: ATP formation

-a. Phosphorylation – another phosphate group added to each substrate

-b. ATP production – substrate level phosphorylation; 2 per molecule; 4 (-2)

-c. NADH+H⁺ - reduced coenzyme NAD+; 1 per molecule; 2 total

-d. Pyruvic acid – 2 molecules; end product of glycolysis

Glucose oxidation: anaerobic versus aerobic

1. Anaerobic – NADH+H⁺ returns hydrogens to pyruvic acid; lactic acid

-a. Lactic acid – diffuse out of cell; back to liver

-b. Acid-base problems – some tissue tolerate (muscle); cardiac less; brain not at all

2. Aerobic – pyruvic acid to mitochondria fluid matrix

Glucose oxidation: Acetyl Coenzyme formation

1. Decarboxylation – one of pyruvic acids carbon removed; CO₂; total 2

2. Oxidation – Hydrogen ions are removed

3. NADH+H⁺- coupled reduction of NAD⁺; total 2

4. Acetic acid – by product

5. Coenzyme A – from pantothenic acid (B₅); combines with acetic acid; acetyl CoA

6. Acetyl CoA – on to Kreb’s cycle

Glucose oxidation: Kreb’s (citric acid) cycle

1. Acetyl CoA – enters the Kreb’s cycle

2. Oxaloacetic acid – combines with acetic acid, which disassociated from CoA

3. Citric acid – where cycle gets its name

4. Decarboxylation – for each acetyl CoA, 2 C removed as 2CO₂; total 4

5. NADH+H⁺ - reduction of NAD⁺; 3 per acetyl CoA; total 6

6. FADH₂ – reduction of FAD; 1 per acetyl CoA: total 2

7. Oxidation – hydrogen removal from intermediates coupled to coenzyme reduction

8. ATP production – GTP; substrate level phosphorylation; 1 per acetyl CoA; total 2

Glucose oxidation: Electron transport chain

1. Cristae – inner mitochondrial membrane; where it takes place

2. Components – of the electron transfer chain; proteins bound to metal ions

-a. Flavins – flavin mononucleotide (FMN); from riboflavin (B₂); to protein

-b. Cytochoromes – iron containing pigments; mostly

3. Respiratory enzyme complex – three of them; grouped together

-a. Coenzyme oxidation – hydrogen is split into H⁺ and e^-; e^- moved along

-b. H⁺ pump – at each complex; use energy from the movement of e^-

-c. Matrix – watery; Hydrogen is pumped out of

-d. Intermembrane space – hydrogen is pumped into

4. ATP synthase – uses electrical energy of H⁺ returning to matrix; makes ATP

5. Reduced cofactors – carry the electron and hydrogen

-a. NADH+H⁺ - each results in movement of 3 H⁺; the production of 3 ATP

-b. FADH₂ – each results in movement of 2 H⁺; production of 2 ATP

6. Oxygen – has the highest affinity for e-; binds to hydrogen

-a. 2H (2H⁺+2e^-) + ½O₂ → H₂O

-b. Physiological water – the water resulting from cellular respiration

7. ATP – 2, glycolysis; 2, Krebs cycle; 34, transport chain; minus 2; 36 ATP

Glycogen metabolism

1. Glycogenesis – high ATP levels, glycolysis stops; glucose stored as glycogen

-a. Hexokinase – in all body cells; uses ATP to ADP to phosphorylate glucose

-b. Glucose-6-phosphate – trapped in most body cells

-c. Glucose-1-phosphate – isomer of G6P

-d. Glycogen synthase – phase in between; glucose added to glycogen chain

-e. Skeletal muscle – does this a lot

-f. Liver – also does this; stores glucose for rest of body

2. Glycogenolysis – from low blood glucose level; glucagon

-a. Glycogen phosphorylase – cleaves off glucose monomers

-b. Glucose-1-phosphate – isomer

-c. Glucose-6-phosphate – can be used in glycolysis

- d. Glucose-6-phosphatease – G6P back to glucose; liver (kidney and intestinal)

Gluconeogenesis

1. Gluconeogenesis – glucose from noncarbohydrate sources; proteins and glycerol

2. Liver – where this takes place

3. Hypoglycemia – the trigger for this to take place

4. Protection – protects nervous system

Lipid metabolism: catabolism

1. Lipolysis – stored fats are broken down to glycerol and fatty acids

2. Glycerol oxidation– to glyceraldehyde phosphate; a glycolysis intermediate

-a. Glyceraldehyde phosphate – plugged into glycolysis; 18 ATP

-b. Gluconeogenesis – all phases of glycolysis are reversible; to glucose-6-phosphate

3. Fatty acids oxidation– are broken down by beta oxidation; in mitochondria

-a. Beta oxidation – fatty acid chains are broken down; from carboxyl side; 2 carbon

-b. Reduced coenzymes – NADH+H⁺ and FADH₂ are formed

-c. Acetic acid – by product of beta oxidation

-d. Acetyl Coenzyme A – formed when acetic acid combines with coenzyme A

-e. Krebs cycle – acetyl Co A enters

4. Ketone bodies – include acetone; from acetyl co A; can’t be fed into Krebs cycle

-a. Ketosis – ketone bodies; diabetes, low carbohydrate diet; metabolic acidosis

Lipid metabolism: anabolic

1. Lipogenesis – reverse of lipolysis; glycerol and fatty acids; dehydration synthesis

-a. Glycerol – from glyceraldehyde phosphate; glycolysis intermediate

-b. Fatty acids – from acetyl coenzyme A

2. Structural materials – many are synthesized from

-a. Cell membrane – phospholipids and cholesterol needed; myelin sheath

-b. Liver – lipoprotein (transport); tissue factor; cholesterol

-c. Cholesterol – from acetyl coenzyme A; steroidal hormones; vitamin D

Amino acid oxidation: catabolic

1. Transamination – in liver, amino and oxygen between amino and keto acids

-a. α-Ketoglutaric acid – keto acid of Krebs cycle, receives amino group

-b. Glutamic acid – amino acid, what the α-ketoglutaric acid

-c. Keto acid – the original amino acid; amino group now an oxygen

2. Oxidative deamination – removal of amino group from glutamic acid

-a. α-Ketoglutaric acid – is reconstituted, back to Krebs cycle

-b. Ammonia – what the amino group becomes; toxic

-c. Urea – ammonia combines with carbon dioxide; removed in urine

3. Keto acid modification – into some intermediate in cellular respiration

-a. Krebs cycle intermediate – acetyl CoA, α-ketoglutaric acid, or oxaloacetic acid

-b. Pyruvic acid – from keto acid modification; used for energy or

-d. Gluconeogenesis – glycolysis is reversible; glucose from pyruvic acid

Proteins / amino acids: anabolic

1. Protein synthesis – mRNA, tRNA; transcription, translation; ribosomes

2. Nonessential amino acids – transamination of keto acids in the liver, mostly

Absorptive state

1. Absorptive state – fed state; nutrients flushing into blood from intestine

2. Anabolism – outweighs catabolic ones

3. Glucose – major fuel; excess stored as glycogen or fat

4. Amino acids – most used to replenish body proteins

5. Triglycerides – broken down, used as fuel; taken up resynthesized by adipose

6. Insulin – released due to high blood glucose; cause body cells to take up glucose

Postabsorptive state

1. Postabsorptive state – empty small intestine; energy from breakdown of reserves

2. Catabolism – breakdown of reserves

3. Glucose – homeostatic mechanism; maintain about 100 mg/ 100 ml blood

-a. Glycogenolysis – liver; skeletal muscle to pyruvic acid, back to liver

-b. Gluconeogenesis – several sources; pyruvic acid from muscle

-c. Glucose sparing – organs which can use other fuels

4. Lipolysis – in liver and adipose tissue

-a. Glycerol – converted to glucose; gluconeogenesis in liver

-b. Fatty acids – directly or used by cells after liver converts to ketone bodies

5. Proteins – after carbohydrate and fats; skeletal muscle first to go

6. Glucagon – causes glycogenolysis and gluconeogenesis; lipolysis of adipocytes

7. Sympathetic nervous system – causes epinephrine release by adrenal medulla

-a. Lipolysis – in adipose tissue increased

-b. Glycogenolysis – stimulated in muscle and liver

-c. Gluconeogenesis – stimulated in liver

Metabolic role of liver: general

1. Carbohydrates – glycogenolysis; glycogenogensis; glucose to lipids

2. Protein metabolism – most plasma proteins; deamination; nonessential AAs

3. Urea – formed to get rid of toxic ammonia from deamination & intestinal bacteria

4. Fats – beta oxidation; acetyl CoA; ketone bodies; cholesterol synthesis

5. Vitamin storage – vitamins A, D, and B₁₂

6. Iron storage – most not in RBCs in liver as ferritin

7. Detoxification – of drugs and alcohol

Metabolic role of liver: cholesterol regulation

1. Chylomicrons – intestine; lymph to blood; lose some triglycerides; back to liver

2. VLDL – from liver; deliver triglycerides to adipose (mostly) and other tissue

3. LDL – from VLDL; cholesterol to body cells; endocytosis

4. HDL – protein shell made in liver; excess cholesterol back to liver; bile salts

BODY ENERGY BALANCE

Regulation of food intake

1. Hypothalamus – control hunger and satiety

2. Nutrient levels – glucose receptors in brain; high glucose levels inhibit hunger

3. Leptin – protein from adipose tissue; high reserve, high leptin, inhibits hunger

4. Insulin – an important satiety signal

5. Other hormones – epinephrine, hunger; cholecystokinin, satiety

6. Body temperature – high temperatures depress hunger

7. Psychological factors – can override automatic factors

8. Hypothetical model – interrelationship of factors that control food intake

-a. Leptin – a satiety signal produced by adipose tissue

-b. Hypothalamus – leptin acts on

-c. Neuropeptide Y – an appetite stimulant produced by hypothalamus, is inhibited

Metabolic rate

1. Metabolic rate – body’s rate of energy output; kcal/hour

2. Calorimeter – direct measure; heat produced by energy raises water temperature

3. Respirometer – indirect measure; oxygen consumption related to energy output

4. Basal metabolic rate – at rest; postabsorptive state; energy for basal functions

-a. 70 kcal/hour – for a normal 70 kg (154 lb)

-b. Influences – age, sex, stress, thyroxine

5. Total metabolic rate – to fuel all organic activities

-a. Skeletal muscle – activity causes greatest increase

-b. Dietary thermogenesis – food intake increases TMR; especially proteins

Regulation of body temperature

1. Body temperature – balance between heat production and heat loss

2. Skeletal muscle – produce much of the heat

3. Average body temperature – 36.2 C (98.2 F); homeostatic range

4. Over homeostatic range – depressed neurons; proteins denature; 106 convulsions

5. Under homeostatic range – more tolerated; used in heart surgery

6. Core body temperature – brain, thoracic and abdominal cavity; constant

7. Shell body temperature – fluctuates 20 to 40 degrees C

8. Heat exchange – always from hotter to colder

-a. Radiation – loss of heat in form of infrared waves

-b. Conduction – direct contact; heat transferred

-c. Convection – air warmed by conduction moved away; replaced by cooler

-d. Evaporation – of sweat; mucosa; water molecules absorb energy; evaporate

9. Hypothalamus – among others; chief controller of body temperature regulation

10. Heat promoting mechanisms – initiated by the hypothalamus

-a. Cutaneous vasoconstriction – slows down heat loss; frostbite

-b. Chemical thermogenesis – norepinephrine; increased metabolic rate

-c. Shivering – involuntary contraction of skeletal muscle

-d. Thyroxine – enhanced release; seasonal changes; gradual; more released, winter

-e. Behavior – more clothes; hot drinks

11. Heat loss mechanisms – again, initiated by the hypothalamus

-a. Cutaneous vasodialtion – increase heat loss to the skin

-b. Sweating – heat loss by evaporation

-c. Behavior – take off clothes; slow down; get out of sun

-d. Heat exhaustion – dehydration; low BP; confusion; cooling mechanism working

-e. Heat stroke – hypothalamus depressed; heat incresses metabolism; brain damage

NUTRITION

General

1. Kilocalorie – energy to raise 1 kilogram water 1 degree Celsius

2. Nutrient – needed for growth, maintenance, and repair

3. Categories – carbohydrates, proteins, lipids, vitamins, minerals, and water

4. Food groups – grains; fruits; vegetable; meat; and dairy

5. Essential nutrients – not synthesized by body; must be obtained in diet

Carbohydrates

1. Sources – complex from starch food; simple from sweet foods

2. Use in body – mostly glucose as fuel; nucleic acids and cell membrane

3. Deficits – proteins and fats broken down; wasting and metabolic acidosis

4. Excesses – obesity; especially simple carbohydrates

Lipids

1. Sources – animal (saturated); plants (unsaturated)

2. Use in body – energy; cell membrane; insulation; padding; hormones

3. Deficits – weight loss; loss of adipose tissue; staying warm

4. Excesses – obesity; atherosclerosis

Proteins

1. Sources – both plant and animal sources

-a. Complete proteins – animal sources; meat; eggs; dairy

-b. Incomplete proteins - plant sources

-c. Essential amino acids – must be obtained from diet

2. Use in body – structure; function (enzymes, hemoglobin); fuel if needed

3. Deficits – tissue wasting; growth retardation; anemia

4. Excesses – obesity

Vitamins

1. Vitamins – organic molecules; coenzyme or part; helps enzyme catalyze

2. Source – most we can’t make; bacteria K and pantothenic acid (B); vitamin D

-a. Provitamin – like β carotene; used to make vitamin A (retinol)

3. Water soluble – C and B complex

-a. Absorption – most with water in GI tract; B₁₂ needs intrinsic factor

-b. Hypervitaminosis – rare with water soluble; not stored in body

4. Fat soluble – A, D, E, and K

-a. Absorption – with fats in GI tract

-b. Hypervitaminosis – all except K can accumulate in body

5. Antioxidants – A, C, and K disarm free radicals; superoxide ion; anticancer

Fat soluble vitamins

1. Vitamin A – retinal; photopigment synthesis; skin, mucosa, skin, bone, repro

-a. Source - β carotene; yellow, green vegetables; liver; egg yolk

2. Vitamin D – antirachitic factor; calcium absorption in intestine

-a. Source – UV light; made in skin; fish liver oil; egg yolk

3. Vitamin E – antisterility factor; antioxidant; protects cell membrane

-a. Source – wheat germ; vegetable oil; nuts

4. Vitamin K – coagulation vitamin; liver synthesis; coagulation and other proteins

-a. Source – mostly enteric bacteria

Water soluble vitamins

1. Vitamin C – ascorbic acid; connective tissue formation; serotonin; bile salts

-a. Source – fruits and vegetable; citrus fruits

2. Vitamin B₁ – thiamine; carbohydrate metabolism

3. Vitamin B₂ – riboflavin; cellular respiration

4. Niacin – nicotinamide; also cellular respiration

5. Vitamin B₆ – pyridoxine; amino acid metabolism

6. Vitamin B₅- pantothenic acid; cellular respiration; fat oxidation and synthesis

7. Biotin – Krebs cycle; nonessential amino acid synthesis

8. B₁₂ – cyanocobalamin; in GI tract; nervous system; red marrow DNA synthesis

9. Folic acid – folacin; amino acid; DNA synthesis; red blood cell formation

Minerals

1. Calcium (Ca) – bones; blood clotting; normal muscle and nervous functioning

-a. Source – dairy; leafy green vegetables

2. Chlorine (Cl) – Cl^- chief anion in extracellular fluid; Cl shift; HCl in stomach

3. Sulfur – proteins (disulfide bonds); vitamins (biotin, thiamine); connective tissue

4. Potassium (K) – intracellular cation; osmotic pressure; nerve, muscle function

5. Sodium (Na) – cation in extracellular fluid; osmotic pressure; neuromuscular

6. Magnesium (Mg) – ATP to ADP; muscle and nerve irritability

-a. Source – dairy; nuts; green vegetables

7. Phosphorus (P) – bone, teeth, nucleic acids, ATP, phospholipids

Trace minerals

1. Fluorine (F) – tooth structure; prevent dental caries; osteoporosis

-a. Source – fluoridated water

2 Cobalt (Co) – part of vitamin B₁₂; red blood cell maturation

3. Chromium (Cr) – glucose metabolism; enhanced effectiveness of insulin

4. Copper (Cu) – hemoglobin synthesis; electron transport chain

5. Iodine (I) – thyroid metabolism

-a. Source – iodized salt; shellfish; cod liver oil

6. Iron (Fe) – hemoglobin; cytochromes in oxidative phosphorylation

7. Manganese (Mn) – synthesis of lipids; hemoglobin; neural function

-a. Source – nuts; legumes; leafy green vegetables

8. Selenium (Se) – antioxidant; spares vitamin E

9. Zinc (Zn) – in several enzymes; carbonic anhydrase