METABOLISM

1
METABOLISM

• GLUCOSE IS THE PRINCIPLE SUBSTRATE USED TO FORM
  ATP

2
GLYCOLYSIS

• OCCURS IN CYTOPLASM
• ANAEROBIC

3
HIGHLIGHTS OF GLYCOYLYSIS

• TWO ATP CONVERTED TO ADP
• FOUR ADP CONVERTED TO ATP
• NET YIELD OF TWO ATP
• TWO NICOTINAMIDE ADENIN DINUCLEOTIDE (NAD)
  PRODUCED
• REDUCTION

4
FATE OF PRODUCTS

• NADH AND PYRUVATE

5
PYRUVATE

• LACTATE FERMENTATION
• KREBS CYCLE

6
ANAEROBIC

• LACTIC ACID FERMENTATIN
• MUSCLE CELLS MAINLY

7
AEROBIC

• KREBS
• ELECTRON TRANSPORT

8
KREBS CYCLE

• MITOCHONDRIA
• DOES NOT DIRECTLY REQUIRE OXYGEN BUT WILL NOT RUN
  WITH OUT IT

9
CONVERSION OF PYRUVATE TO ACETYL CO A

• TECHNICALLY NOT PART OF KREBS
• OCCURS IN INTERMEMBRANAL SPACE
• PRODUCTS INCLUDE ACETYL COA
• CARBON DIOXIDE
• NADH

10
ACETYL CO ENZYME A

• ENTRY MOLECULE FOR THE KREBS CYCLE

11
KREBS CYCLE

• BEGINS WITH OXALOACETATE
• ENDS WITH OXALOACETATE
• CITRATE BINDS WITH ACETYL COA
• NADH
• FADH2
• CARBON DIOXIDE

12
FATE OF PRODUCTS

• NADH AND FADH2 -- ETS
• CARBON DIOXIDE -- AWAY

13
ELECTRON TRANSPORT

• SET OF ELECTRON CARRIERS
• OXIDATION -- REDUCTION REACTIONS
• COENZYMES
• PROTEINS
• OXYGEN IS FINAL ELECTRON

14
NADH DEHYDROGENASE COMPLEX

• COENZYE Q SHUTTLES ELECTRONS TO NEXT COMPLEX

15
CYTOCHROME REDUCTASE COMPLEX

• CYTOCHROME C SHUTTLES ELECTRONS TO THIRD COMPLEX

16
CYTOCHROME OXIDASE COMPLEX

• ELECTRONS ARE PASSED TO WATER BY CYTOCHROME
  OXIDASE

17
ELECTROCHEMICAL PROTON GRADIENTS

• ELECTRONS LOSE ENERGY AS THE PASS DOWN ETS
• ENERGY IS USED TO PUMP PROTONS OUT INTO
  INTERMEMBRANE SPACE

18
IMPORTANCE OF PROTON GRADIENT

• MORE CHARGES LEADS TO VOLTAGE GRADIENT

19
ATP SYNTHETASE

• ASSOCIATED WITH INNER MEMBRANE
• ONLY PATH FOR H TO REACH MATRIX
• ENERGY RELEASED CAN BE USED TO MAKE ATP

20
ENERGY YIELD

• ONE ATP IS PRODUCED FOR EVERY TWO ELECTRONS THAT
  PASS THROUGH AN ATPase COMPLEX

21
WHY WE GET A YIELD OF 36-38 ATP

• NADH VS FADH2

22
NADH

• DONATES PAIR OF ELECTRONS TO NADH DEHYDROGENASE
  COMPLES
• ELECTRONS PASS THROUGH ALL THREE COMPLEXES
• MAKE THREE ATPs

23
FADH2

• DONATES ELECTRONS TO COENZYME Q.
• DOES NOT PASS THROUGH NADH DEHYDROGENASE COMPLEX
• PRODUCE ONLY TWO ATPs

24
BLAME IT ALL ON THE OUTER MEMBRANE

• MALIC ACID VS GLYCERAL PHOSOPHATE SHUTTLES

25
MALIC ACID SHUTTLE

• GIVES ELECTRONS TO NADH
• 3 ATPS
• LIVER AND HEART HAVE LOTS

26
GLYCEROL PHOSPHATE SHUTTLE

• GIVES ELECTRONS TO FADH2

27
ENERGY YIELD FROM GLUCOSE BREAKDOWN
28
AEROBIC

• 36-38 ATP
• TWO FROM GLYCOLYSIS
• TWO FROM KREBS
• 32-34 FROM ELECTRON TRANSPORT

29
SUBSTRATE VS OXIDATIVE PHOSPHORYLATION
30
WHY WE USE METABOLIC PATHWAYS

• UNCONTROLLED COMBUSTION PRODUCES 686,000 calories
  PER MOLE
• BREAKING DOWN IN SMALL STEPS WE OPTIMALLY (38
  ATP) PUT 40 OF ENERGY INTO ATP
• 60 LOST AS HEAT
• ATP YEILD IS GENERALLY LOWER

31
METABOLISM

• AMINO ACIDS AS ENERGY SOURCES

32
AMINO ACID METABOLISM

• LOSE AMINO GROUPS
• ALPHA KETO ACIDS THAT ENTER THE KREBS CYCLE AS
  PYRUVIC ACID OR OXALOACETATE

33
TRANSAMINATION REACTIONS

• AMINO GROUP OF AMINO ACID IS EXCHANGED FOR OXYGEN
  OF ALPHA KETO ACID
• ALPHA KETOGLUTARATE IS MOST COMMON

34
FATE OF MOLECULES

• ORIGINAL AMINO ACID BECOME ALPHA KETO ACID AND
  CAN BE THROWN INTO KREBS
• ALPHA KETOGLUTARATE BECOMES GLUTAMIC ACID AND
  UNDERGOES OXIDATIVE DEAMINATION

35
OXIDATIVE DEAMINATION

• AMINO ACID GROUP IS REMOVED
• CONVERTED TO AMMONIA
• ALPHA KETOGLUTARATE

36
METABOLISM

• TRIGLYCERIDES

37
PRODUCTS OF TRIGLYCERIDE HYDROLYSIS

• GLYCEROL
• FATTY ACIDS

38
GLYCEROL

• CAN BE PLUGGED INTO GLYCOLYSIS AS DHAP
• CONVERTED TO GYCERALDEHYDE -3- PHOSPHATE

39
BETA OXIDATION OF FATTY ACIDS

• BROKEN DOWN INTO MOLECULES ACETYL CO A
• MAY ENTER THE KREBS CYCLE

40
USES OF CATABOLIC PRODUCTS FOR ANABOLISM

• PRODUCTS AND INTERMEDIATES MAY BE USED TO BUILD
  LARGER MOLECULES
• ALLOWS BODY TO SYNTHESIZE MANY PRODUCTS THEY NEED

41
ESSENTIAL NUTRIENTS

• CAN NOT BE MADE BY BODY MUST BE INCLUDED IN DIET
• SOME AMINO ACIDS
• SOME FATTY ACIDS
• VITAMINS

42
NUTRIENT POOLS

• MATERIALS THE BODY CAN DRAW UPON DURING PERIODS
  OF NEED
• MUSCLE PROTEIN --PROVIDES AMINO ACID
• ADIPOSE TISSUE -- PROVIDES FATTY ACIDS
• CARBOHYDRATES CAN BE CONVERTED TO LIPIDS

43
METABOLIC STATES

• ABSORPTIVE VS POSTABSORPTIVE STATE

44
ABSORPTIVE STATE

• CARBOHYDRATE
• PROTEIN
• TRIGLYCERIDE

45
TYPICAL MEAL

• 65 CARBOHYDRATE
• 25 PROTEIN
• 10 TRIGLYCERIDE

46
CARBOHYDRATE

• GLUCOSE IS MAJOR ENERGY SOURCE
• EXTRA STORED AS GLYCOGEN AND TRIGLYCERIDES

47
ABSORBED CARBOHYDRATES

• GLUCOSE
• GALACTOSE
• FRUCTOSE
• MOST OF GALACTOSE AND FRUCTOSE IS CONVERTED TO
  GLUCOSE OR ENTERS SAME METABOLIC PATHWAYS

48
HEPATIC PORTAL VEIN SYSTEM

• CARRIES ABSORBED CARBOHYDRATES AND AMINO ACIDS TO
  LIVER

49
LIVER

• REMOVES LARGE PORTION OF CARBOHYDRATES
• USES LITTLE ITSELF
• CONVERTS TO TRIGLYCERIDE OR GLYCOGEN

50
GLYCOGEN

• STORED IN LIVER

51
TRIGLYCERIDES

• SOME STORED IN LIVER
• MOST PACKAGED INTO VERY LOW DENSITY LIPOPROTEINS
  (VLDLs)
• RELEASED INTO BLOOD

52
VERY LOW DENSITY LIPOPROTEINS

• TRIGLYCERIDES
• CHOLESTEROL
• PHOSPHOLIPIDS
• PROTEINS

53
ADIPOSE CELLS AND CARBOHYDRATES

• CAN PICK UP GLUCOSE IN BLOOD AND CONVERT TO
  TRIGLYCERIDES

54
SKELETAL MUSCLE

• CAN PICK UP GLUCOSE AND CONVERT TO GLYCOGEN

55
PROTEIN

• AMINO ACIDS CAN BE PICKED UP BY A VARIETY OF
  TISSUES
• USED FOR PROTEIN SYNTHESIS, LIPID SYNTHESIS,
  ENERGY PRODUCTION

56
LIVER

• CONVERTS TO ALPHA KETO ACID USED FOR ENERGY
  OR TRIGLYCERIDE PRODUCTION
• USE TO MAKE PLASMA PROTEINS

57
SKELETAL MUSCLES

• TAKE UP AMINO ACIDS AND USED FOR PROTEIN SYNTHESIS

58
TRIGLYCERIDES

• ENTERS LACTEALS OF LYMPHATIC SYSTEM
• CARRIED IN CHYLOMICRONS
• PICKED UP BY SKELETAL MUSCLE AND ADIPOSE TISSUE

59
LIPOPROTEIN LIPASE

• ENZYME ASSOCIATED WITH CAPILLARY ENDOTHELIUM OF
  CAPILLARIES
• SKELETAL AND ADIPOSE TISSUES
• BREAKS DOWN TRIGLYCERIDES OF CHYLOMICRONS VERY
  LOW DENSITY LIPOPROTEINS
• RELEASES FREE FATTY ACIDS

60
FATE OF FATTY ACIDS

• USED AS ENERGY SOURCE
• RESYNTHESIZED INTO TRIGLYCERIDES

61
SUMMARY OF ABSORPTIVE USE OF NUTRIENTS
62
POSTABSORPTIVE STATE

• MAINTENANCE OF BLOOD GLUCOSE

63
SOURCES OF GLUCOSE

• GLYCOGEN STORES OF LIVER
• SUPPORT BODY FOR ABOUT FOUR HOURS
• PYRUVATE AND LACTATE PRODUCED BY MUSCLES
• GLYCEROL FROM FATTY ACID HYDROLYSIS
• PROTEIN STORES (MAINLY MUSCLE)

64
GLUCONEOGENESIS

• PROTEIN MAJOR SOURCE OF GLUCOSE IN PROLONGED
  FASTING
• NONESSENTIAL MUSCLE PROTEINS
• PROTEINS IN OTHER TISSUES TO A LESSER EXTENT
• KIDNEYS MAY PARTICIPATE IN PROLONGED FAST

65
GLUCOSE SPARING

• ALMOST ALL TISSUES USE LITTLE GLUCOSE
• DEPEND ON TRIGLYCERIDES
• SPARES GLUCOSE FOR NERVOUS SYSTEM

66
TRIGLYCERIDE USE IN THE POSTABSORPTIVE STATE

• ADIPOSE TISSUE TRIGLYCERIDE USED
• FREE FATTY ACIDS TAKEN OUT OF BLOOD
• PLUGGED INTO KREBS CYCLE

67
ROLE OF THE LIVER IN THE POSTABSORPTIVE STATE

• USES FATTY ACIDS AS ENERGY SOURCE
• PRODUCES KETONE BODIES AND THROW THEM INTO
  BLOODSTREAM
• TISSUES PICK THEM UP AND THROW THEM INTO KREBS
  CYCLE

68
IMPORTANCE OF TRIGLYCERIDE USE

• SPARES GLUCOSE FOR USE BY NERVOUS SYSTEM
• NERVOUS SYSTEM ONLY WANTS TO USE GLUCOSE

69
KETONE USE BY THE NERVOUS SYSTEM

• PROLONGED FASTS WILL CAUSE CHANGES IN BRAIN
  METABOLISM
• MANY BRAIN AREAS CAN USE KETONE BODIES
• THIS CONSERVES PROTEINS

70
MECHANISMS OF CONTROL FOR THE ABSORPTIVE AND
POSTABSORPTIVE STATES

• HORMONAL AND NEURAL

71
NEURAL

• SYMPATHETIC
• PARASYMPATHETIC

72
SYMPATHETIC

• DURING ACUTE HYPOGLYCEMIA
• INCREASED STIMULATION TO LIVER, ADIPOSE TISSUES,
  ADRENAL MEDULLA
• STIMULATES GLYCOGENOLYSIS
• LIPOLYSIS

73
GLYCOGENOLYSIS
74
LIPOLYSIS
75
HORMONAL

• INSULIN
• GLUCAGON
• EPINEPHRINE

76
CHOLESTEROL METABOLISM

• DIETARY AND INTRINSIC SOURCES

77
LIPOPROTEINS

• VERY LOW DENSITY LIPROTEINS
• LOW DENSITY LIPOPROTEINS
• INTERMEDIATE LIPOPROTEINS
• HIGH DENSITY LIPOPROTEINS
• CHYLOMICRONS

78
LIPOPROTEIN RELATIONSHIPS

• LIPOPROTEIN LIPASE BREAKS DOWN CHYLOMICRON
  TRIGLYCERIDES
• VLDLs ARE PRODUCED BY LIVER, RELEASED INTO BLOOD
• LIPOPROTEIN LIPASE BREAKS DOWN VLDL TRIGLYCERIDES
• VLDLs BECOME IDLs

79
FATE OF IDLs

• SOME TAKEN UP BY LIVER
• OTHERS ARE CONVERTED INTO LDLs
• LDLs ARE MAJOR CHOLESTEROL CARRIER IN THE BLOOD
• HDLs PICK UP CHOLESTEROL RELEASED FROM CELLS AND
  TRANSFER IT TO LDLs

80
CHOLESTEROL REGULATION

• MANY CELLS CAN PRODUCE CHOLESTEROL
• MOST GET THEIR SUPPLY FROM LDLs
• LDLs BINDTO RECEPTORS ON CELL MEMBRANE
• TAKEN IN BY RECEPTOR MEDIATED ENDOCYTOSIS

81
CELLS REGULATE THEIR UPTAKE

• HIGH CHOLESTEROL--FEWER RECEPTORS
• LOW CHOLESTEROL -- MORE RECEPTORS

82
HDLs AND THE CELLS

• ALSO BIND TO CELLS
• SIGNALS CELL TO RELEASE CHOLESTEROL
• HDLs CAN PICK UP CHOLESTEROL
• LOW CHOLESTEROL SUPPRESSES PRODUCTION OF
  CHOLESTEROL

83
THE ROLE OF THE LIVER IN CHOLESTEROL METABOLISM

• MAJOR SITE OF PRODUCTION
• RELEASES VLDLs
• SYNTHESIZES BILE SALTS FROM CHOLESTEROL
• TAKES UP CHYLOMICRON REMNANT
• TAKES UP IDLs
• TAKES UP LDLs

84
CHOLESTEROL AND ATHEROSCLEROSIS

• HIGH LDLs MAY BE LINKED WITH INCREASED RISK
• HIGH HDLs MAY BE LINKED WITH LESSER RISK

85
WHY YOU WILL NEVER BE FREE OF CHOLESTEROL

• BODY CELLS CAN MAKE
• MAKES IT NEARLY IMPOSSIBLE TO SUBSTANTIALLY
  REDUCE BY DIET ALONE
• NEED TO GET RID OF ANIMAL FATS
• LOW FAT -- LOW CHOLESTEROL DIET WITH LIMITED
  ANIMAL FAT

86
VITAMINS

• DO NOT PROVIDE ENERGY
• ARE NOT STRUCTURAL COMPONENTS
• CANNOT BE SYNTHESIZED GENERALLY

87
VITAMINS ARE

• COFACTORS OR COENZYMES
• CATALYSTS
• WATER SOLUBLE OR FAT SOLUBLE
• GENERALLY PROVIDED BY DIET

88
WATER SOLUBLE VITAMINS

• B VITAMINS
• VITAMIN C

89
FAT SOLUBLE VITAMINS

• A, D , E, AND K
• ABSORBED WITH TRIGLYCERIDES

90
VITAMIN STORAGE

• LITTLE WATER SOLUBLE IS STORED
• MAINLY FAT SOLUBLE
• MAINLY IN LIVER

91
MINERALS

• MAKE UP 4-5 OF BODY WEIGHT
• MANY ENZYMES NEED THEM
• GENERALLY IN IONIZED FORM

92
METABOLIC RATE

• TOTAL ENERGY EXPENDE BY THE BODY PER UNIT TIME
• USED FOR BIOLOGICAL WORK
• ALSO HEAT
• ONLY SMALL AMOUNT OF ENERGY USED FOR WORK

93
METABOLIC RATE AND OXYGEN

• CAN MAKE A REASONABLE ESTIMATE BY MEASURING RATE
  OF OXYGEN CONSUMPTION
• FOR EVERY LITER CONSUMED THE BODY PRODUCES 4,845
  KILOCALORIES OF ENERGY

94
BASAL METABOLIC RATE

• BODYS METABOLIC RATE UNDER CONTROLLED CONDITIONS
• AWAKE
• AT REST
• ROOM BETWEEN 20 TO 25 DEGREE C
• POSTABSORPTIVE STATE
• 12-18 HOURS SINCE LAST MEAL

95
LOWEST METABOLIC RATE

• SLEEP
• 10-15 LOWER THAN BASAL METABOLIC RATE

96
FACTORS THAT AFFECT METABOLIC RATE

• SEX
• AGE
• FOOD INGESTED

97
SEX AND THE METABOLIC RATE

• MALES HIGHER
• FEMALES LOWER
• TENDS TO INCREASE UNTIL WE ARE TWO OR THREE AND
  THEN DECREASE

98
FOODS

• TYPICAL MEAL CONTAINING CARBOHYDRATE, PROTEIN AND
  FAT
• INCREASES METABOLIC RATE 10-15

99
SPECIFIC DYNAMIC ACTION

• FOOD INDUCED THERMOGENESIS
• PROTEIN HAS GREATEST EFFECT IF INGESTED ALONE
  CAN INCREASE METABOLISM AS MUCH AS 30
• CARBOHYDRATE ALONE MAY INCREASE METABOLISM ABOUT
  5
• LIPID ALONE INCREASES METABOLISM BY ABOUT 8

100
REASONS FOR INCREASE

• SMALL AMOUNT DUE TO DIGESTION AND ABSORPTION
• MOST DUE TO PROCESSING BY LIVER
• GREATEST CHANGES ARE PRODUCED BY MUSCLES
• EXERCISE CAN INCREASE BY 15 TIMES

101
REGULATION OF BODY ENERGY BALANCES

• GLUCOSTATIC THEORY
• LIPOSTATIC THEORY
• THERMOSTATIC THEORY

102
GLUCOSTATIC THEORY

• BRAIN CONTAINS GLUCOSE RECEPTORS
• SENSITIVE TO OWN RATE OF GLUCOSE UTILIZATION
• HIGH GLUCOSE CAUSES SUPPRESSION OF HUNGER
• LOW GLUCOSE CAUSES HUNGER

103
LIPOSTATIC THEORY

• SUBSTANCE RELEASED FROM FAT STORE ARE RELEASED IN
  PROPORTION TO TOTAL ADIPOSE TISSUE MASS
• GREATER TOTAL MASS LESS FOOD CONSUMED

104
THERMOSTATIC THEORY

• BRAIN AREAS THAT CONTROL BODY TEMPERATURE
  INTERACT WITH CENTERS THAT CONTROL FEEDING
• HIGHER TEMPERATURES TEND TO DEPRESS
• LOWER TEMPERATURE TEND TO INCREASE

105
HORMONES THAT AFFECT FEEDING

• INSULIN
• CCK

106
PSYCHOLOGICAL FACTORS

• TASTE
• SMELL
• TEXTURE
• STRESS
• ANXIETY
• DEPRESSION

107
REGULATION OF BODY TEMPERATURE

108
BODY TEMPERATURES

• ABOUT 37 DEGREES C
• FLUCTUATES DURING DAY ON CIRCADIAN CYCLE
• LOWEST TEMP IN MORNING
• HIGHEST IN EVENING
• DIFFERENT TEMPERATURES IN DIFFERENT PARTS OF BODY

109
WARM ENVIRONMENTS

• DECREASE IN MUSCLE TONE

110
COLD TEMPERATURES

• INCREASE IN MUSCLE TONE
• MAY LEAD TO TREMORS

111
CHRONIC EXPOSURE TO COLD TEMPERATURES

• EPINEPHRINE SECRETION
• THYROID HORMONE MAY BE INVOLVED

112
MECHANISM BY WHICH HEAT MAY BE LOST

• RADIATION
• CONDUCTION
• CONVECTION
• EVAPORATION

113
RADIATION

• ALL DENSE OBJECTS EMIT HEAT
• AS INFARED RAYS
• EXHANGE OF HEAT WITH OBJECT IN ENVRIRONMENT
• NET DIRECTION DEPENDS ON SURFACE TEMPERATURE OF
  OBJECTS
• WARMER TO COOOLER

114
CONDUCTION

• TRANSFER OF HEAT FROM ONE ATOM OR MOLECULE TO
  ANOTHER
• FROM HIGHER TEMPERATURE TO LOWER TEMPERATURE
• AIR TO BODY

115
CONVECTION

• WARM AIR RISES
• COLD AIR SINKS
• COOL AIR CONSTANTLY BROUGHT INTO CONTACT WITH SKIN

116
EVAPORATION

• HEAT OF VAPORIZATION
• APPROXIMATELY 580 CALORIES PER GRAM OF WATER
• THIS CARRIES HEAT AWAY FROM BODY

117
WATER LOSS FROM BODY SURFACES

• INSENSIBLE
• SENSIBLE OR SWEATING

118
CONTROL OF CUTANEOUS BLOOD VESSELS AND HEAT
REGULATION

• BLOOD VESSELS DILATE IN RESPONSE TO WARM
  TEMPERATURES
• BLOOD VESSELS CONSTRICT IN REPSONSE TO COLD
  TEMPERATURES

119
CONTROL OF TEMPERATURE BY CNS

• HYPOTHALAMUS

120
Possible fates of amino acids