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METABOLISM
Metabolism
1. Metabolism – all chemical reactions necessary to maintain life
2. Catabolism – breakdown from complex to simple
*Chemical reactions in which complex molecules are broken down to simple ones:
a. anabolism
b. catabolism
c. reduction
d. oxidation
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)
*This results from the gain of hydrogen or loss of oxygen:
a. anabolism
b. catabolism
c. reduction
d. oxidation
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
*This coenzyme is derived from riboflavin:
a. ATP
b. cyclic AMP
c. FAD
d. NAD+
-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
*All carbohydrates are broken down to this:
a. glucagon
b. glucose
c. glycine
d. glycogen
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
*The end product of glycolysis is:
a.
b.
c.
d.
glycerol
glycogen
acetyl coenzyme A
pyruvic acid
*Glycolysis results in the net formation of _____ molecules of ATP per glucose:
a.
b.
c.
d.
1
2
8
16
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
*This molecule enters the Kreb’s cycle:
a. acetone
b. acetyl CoA
c. lactic acid
d. pyruvic acid
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
*The electron transport chain is located here:
a. cytosol
b. inner mitochondrial membrane
c. outer mitochondrial membrane
d. plasma membrane
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
*ATP synthase uses the movement of this ion to make ATP:
a. calcium
b. hydrogen
c. potassium
d. sodium
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
*Glucose-6-phosphate can be converted back to glucose here:
a. adipose tissue
b. adrenal gland
c. cardiac muscle
d. liver
-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
*Fatty acids are broken down by:
a. alpha oxidation
b. beta oxidation
c. alpha reduction
d. glycolysis
-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
*Too many of these by products lipolysis can lead to acidosis:
a. glycerol
b. glycine
c. ketone bodies
d. cholesterol
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
*Oxidative deamination of glutamic acid results in the release of this toxic substance:
a. ammonia
b. carbon monoxide
c. lactic acid
d. pyruvate
-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
*The formation of most nonessential amino acid occurs here:
a. intestine
b. liver
c. kidney
d. skin
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
*During the absorptive state this is the major fuel used by the body:
a. amino acids
b. lipids
c. glycogen
d. glucose
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
*Of the following which is less likely to occur during the postabsorptive state?
a. lipid synthesis
b. glycogenolysis
c. gluconeogenesis
d. glucose sparing
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
*These lipoproteins transport excess cholesterol back to the liver:
a. chylomicrons
b. VLDL
c. LDL
d. HDL
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
*This part of the brain controls hunger:
a. basal nuclei
b. thalamus
c. hypothalamus
d. pineal
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
*Of the following which is not a fat soluble vitamin?
a. A
b. B
c. D
d. E
-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