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Transcript
Saladin Ch. 26 Nutrition & Metabolism
I. NUTRITION
Body weight & energy balance
30 – 50% of variation in human body weight is heredity, rest is environmental factors –
eating & exercise habits.
Appetite
Many peptide hormones & regulatory pathways are involved in short & long term
appetites control
Short term regulators
Ghrelin – from stomach – sensation of hunger + stimulates hypothalamus to release
GHRH.
Peptide YY [PYY] – from ileum & colon – secreted with feeding – proportional to
calories consumed – stop eating signal.
CCK – from SI – stimulates secretion of bile & pancreatic enzymes. – Also causes
appetite suppressing effect on vagus – a stop eating signal
Long term regulators
Leptin – from adipocytes – proportional to levels of body fat – most human obesity
related to leptin is due to receptor defect, not hormone defect.
Insulin – from pancreas – receptors in brain – functions like leptin - weaker
Brain center = arcuate nucleus of hypothalamus – 2 groups of neurons
1 – secretes neuropeptide Y – stimulates appetite
2 – secretes melanocortin – inhibits eating
Gastric peristalsis also stimulates hunger
Neurotransmitters influence types of food consumed
Norepinephrine – CBH
Galanin – fat
Endorphins - protein
Obesity – more than 20% above norm for demographic. In US 30% are obese and an additional
35% are overweight.
Predisposition to obesity is increased by over-feeding in infancy and early childhood.
Calories
Calorie - amount of heat required to raise one gram of water one degree Celsius.
Kilocalorie [the dietary Calorie} = 1000 calories.
Energy yields of nutrients
Carbohydrate - 4Kcal/g
Lipid - 9 Kcal/g
Protein - 4 Kcal/g
Nutrients
Any ingested chemical that is used for growth, repair or maintenance.
Required dietary Nutrients – review RDA, Table 26.1
Carbohydrates
Fates of CBH’s
ATP production – aerobic respiration, anaerobic fermentation
Glycogen & adipose storage
Amino Acid synthesis
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Structural component of nucleotides, glycoproteins, glycolipids
Excretion – spill over onto urine
Neurons & erythrocytes depend almost entirely on CBH
Review Insulin/glucagon homeostasis – Ch 17; CBH in API notes
Requirements – higher than other nutrients
Sources – plants
Fiber – resist digestion – plant & animal forms.
Promotes intestinal function. Water soluble forms reduce blood cholesterol &
LDL’s.
Blood sugar levels – 70 -110 mg/dL = normal range.
Lipids
Fatty acids, glycerol, cholesterol
Meet 80 – 90% of resting energy needs
Required for absorption of fat soluble vitamins
Membrane & hormone structural components.
Needs – no more than 30% of diet – most should be unsaturated; must get linoleic acid
from diet – rest appear to be able to be made.
Cholesterol Metabolism
Structural unit of bile salts, steroids, Vitamin D and cell membranes.
15% of blood cholesterol is from diet
85% is made by the body
Cholesterol & Lipoproteins - transported as spheres
The spheres are lipoproteins – hydrophobic triglycerides and cholesterol esters are in the
interior, hydrophilic phospholipid heads, cholesterol and proteins are on the exterior
surface.
Classes
Chylomicrons – 2% protein, 90% triglyceride, 3% phospholipid,
5% cholesterol
VLDL – 8% protein, 55% triglycerides, 17% phospholipid, 20%
cholesterol
LDL (bad cholesterol – gets deposited in blood vessels) 20% protein, 6%
triglyceride, 21% phospholipid, 53% cholesterol – gets deposited in vessel
walls [from adipose].
HDL – 50% protein, 5% triglyceride, 25% phospholipid, 20%
cholesterol (good cholesterol) cleared by liver – no vascular buildup.
[transport TO liver]
Desirable levels
Total cholesterol - < 200mg/dL
LDL < 130mg/dL
HDL > 40mg/dL [60 or higher gives some
protection against heart disease]
Total <200mg/dL
Ratio of total/HDL <4 desired
Bad
LDL > 159 mg/dL
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Total > 239 mg/dL
Factors regulating plasma cholesterol
Increased dietary cholesterol decreases liver production, BUT doesn’t stop it.
Saturated fatty acids increase liver synthesis and decrease excretion
Unsaturated fatty acids increase excretion
Hydrogenated fats increase LDL’s and decrease HDL [worst effect of all]
Proteins
 amino acids
8 essential amino acids - we don't make or can't make enough isoleucine, leucine, lysine, methionine, phenylalanine, threonine,
tryptophan, valine, histidine, arginine
12 non-essential - synthesized by the body by transamination.
Not stored – must be present when needed from ingestion.
Nitrogen balance – when in = out – positive with growth, negative with insufficiency.
Vitamins & Minerals
Vitamins – review table 26.3 - fat soluble - A, D, E, K
Water soluble - B1, B2, niacin, B6, B12, Folic acid, C
Minerals – review table 26.2 - Ca, P, Fe, I, Cu, Na, K, Cl, Mg, S, Zn, F, Mn
II. CARBOHYDRATE METABOLISM
All oxidative CBH consumption is essentially glucose catabolism
C6H12O6 + 6O2  6H2O +6CO2 + ATP [+heat]
Glucose catabolism – glycolysis, anaerobic fermentation, aerobic respiration
Mechanisms - Redox
Reduction reactions add electrons to substances.
Oxidations remove electrons [stepwise removal of pairs]
They are always coupled – the electrons given in the reduction are equal in
number to the ones removed in the oxidation.
In biologic systems, the most common oxidation process generates 2 H’s plus 2 electrons.
These associate with a co-enzyme – either one or both H’s binds [one may be released].
Ex. NAD+ [nicotinamide adenine dinucleotide] is in the oxidized state. It receives the
pair to form NADH and H+. Other co-enzymes include NADP+ and FAD+ [flavin
adenine dinucleotide]
Glycolysis – occurs in cytoplasm – converts glucose to pyruvate
Immediately upon entry into the cell, glucose is converted to glucose-6-phosphate
10 steps –SEE HANDOUT and Figure 26.3
Ends [for 1 glucose] 2 pyruvates, 2 net ATP and 2NADH + 2H’s
Anaerobic fermentation
Glucose Metabolism in the Absence of Oxygen
Lactic acid fermentation – in muscle cells
Starts with pyruvate and NADH
Produces lactic acid and NAD+. Lactic acid can be used in liver
for glucose synthesis.
Renews NAD+ in cytoplasm for continued ATP production.
Matrix reactions
Starts with pyruvate, NAD+ and Coenzyme A [CoA] --> AcetylCoA + CO2 +
NADH + H+
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Runs twice per original glucose  2 Acetyl CoA’s
Kreb’s Cycle – in matrix of mitochondrion
8 steps – SEE Handout
Starts with Acetyl CoA, oxaloacetic acid, NAD+, FAD+
Runs twice per original glucose molecule
Ends - [with 2 pyruvates] 6CO2 + 2 ATP + 8 NADH + 8H+ + 2FADH2
Membrane reactions - oxidize NADH & FADH2 to move electrons, & regenerate NAD+
& FAD+
Electron Transport System – on inner mitochondrial membrane – cristae - pumps H+ ions
for Chemiosmosis.
Need electron carriers – pass electrons from one carrier to another by
paired redox reactions.
Carriers = Flavin Mononucleotide [FMN], cytochromes, Fe-S centers, Cu,
Coenzyme Q.
3 pumps present
1 – NADH dehydrogenase complex – FMN and 5 Fe-S centers – start – NADH +
H+ is oxidized to NAD+ and FMN is reduced to FMNH2. This is oxidized--- and
so on down line – Ends with Coenzyme Q – a mobile carrier that transports the
electrons it receives to the next pump.
2 – Cytochrome b-c1 complex – electrons passed from Q to cyt b --- to cyt c –>
passes electrons to next pump
3 – cytochrome oxidase complex – receives electrons from cyt c and passes them
to Cu then to cyt a, cyt a3 and then to O. The negative O picks up 2 H+  H2O
[only place in respiration where O is consumed!!!]
Energy from step-wise release powers pumping H+ into intermediate space by
chemiosmosis
The concentration of H+ outside > than that inside – this produces an electrostatic
gradient and a net voltage.
Since it is positive charges – it is called proton motive force instead of electromotive
force (from electron distribution).
Facilitated diffusion channels containing enzymes for ATP formation [ATP synthase]
allow the H+ to move back across the membrane driven by this force.
The energy from the force is used for the ATP production.
ENERGY YIELD OF CELLULAR RESPIRATION [2-3 ATP/NADH, 2 ATP/FADH2]
Step
Products
Energy[with O]
without O
Glycolysis
2ATP
2
ATP
2ATP
2NADH
4 - 6 ATP
Transition
2NADH
6
ATP
Krebs
2ATP
2
ATP
6NADH
18
ATP
2FADH2
4 ATP
Totals
36 - 38 ATP
2 ATP
Glycogen metabolism [glucose is stored, not ATP]
Glycogenesis – glucose converted into glycogen for storage
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In liver and skeletal muscle
Stimulated by insulin
Glucose is converted to Glucose – 6 phosphate.
Glucose –6 – phosphate is converted to glucose -1-phosphate which
is converted to glycogen
Glycogenolysis – gets glucose out of glycogen
In liver
Stimulated by glucagon and epinephrine
Glycogen cleaved  releases glucose-1-phosphate.
Glucose-1-phosphate is converted to glucose-6-phosphate
Glucose-6phosphate is converted to glucose or can enter glycolysis.
Gluconeogensis – In liver, making of new glucose –from protein and or fat
Stimulated by cortisol, glucagons, epinephrine
Liver disorders
Hepatitis - inflammation - viral usually - 5 strains
A most common - transmitted in large restricted groups & by foods
B & C are sexually transmitted & by blood and fluids.
Symptoms - Fatigue, malaise, nausea, weight loss
III. LIPID & PROTEIN METABOLISM
Lipids
Lipid Transport – most non-polar lipids complex with protein made in the
liver and intestines to produce water soluble spheres [see above]
Lipogenesis
In liver and adipose
Glucose or amino acids converted into lipids
Glucose  glyceraldehyde  glyceraldehyde-3-phosphate  glycerol or
to acetyl CoA which can go on to form fatty acids
Amino acids  Acetyl CoA  fatty acids, etc.
Stimulated by Insulin
Lipolysis
Liver. First lipids are split into glycerol & fatty acids by lipases.
Then, by beta oxidation, cleaves the A's into 2C fragments and attaches them
to CoA to form Acetyl CoA for Kreb’s cycle, or converts 2Acetyl CoA’s to
acetoacetic acid & then to beta-hydroxybutyric acid and acetone [all 3 are called
ketone bodies] Too much  acidosis
Proteins
Protein metabolism
Amino Acids are either used to make other proteins, glucose or triglycerides or
ATP, they are not stored.
Use as fuel
Proteins are broken down to amino acids  Deamination in liver allows them to
enter the Kreb's cycle
For Kreb's - aa is converted to acetyl CoA or an acid in the cycle
For gluconeogenesis - the amino less acid is converted to pyruvate and
Other molecules that can enter the Kreb’s cycle.
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Transamination, ammonia & urea
Amino group  ammonia  urea
Amino group is transferred to citric acid --> --> glutamic acid --> liver -->
removal of NH2 --> ammonia --> urea
Protein synthesis - occurs on ribosomes, directed by DNA and RNA
Amino acids joined by peptide bonds
Stimulated by GH, Insulin, T3, T4, estrogen and testosterone
IV. METABOLIC STATES & METABOLIC RATE
Absorptive State - During digestion
Ingested nutrients enter blood and lymphatic system --> hepatic portal system to liver
Lasts about 4 hours after completing a meal
Events:
Glucose
Glucose uptake by liver  converted to triglycerides and glycogen (10%)
Adipose tissues store fat take up blood glucose  to triglycerides (40%)
Muscles take up glucose and store as glycogen (50%)
Amino Acids  liver  Kreb's cycle or gluconeogenesis or protein synthesis
Lipids most packaged  VLDL lipoproteins and are carried to adipose.
Hormones -mostly, insulin [hypoglycemic hormone]
Post Absorptive State - fasting
Need to maintain normal blood glucose level [90-100mg/100mL]
Very important for nervous system - can only use glucose for energy.
EVENTS:
Liver glycogen is converted to glucose - lasts about 4 hrs.
Muscle glycogen is converted to lactic acid  glucose in liver
Adipose breaks triglycerides to glycerol  glucose
Muscle protein  aa  converted by liver into glucose [gluconeogenesis]
Hormone – glucagon; Neural Control – ANS via epinephrine
Metabolic rate
Basal metabolic rate [BMR] - rate of metabolism measured under standard conditions awake, resting, fasting. Units = Kcal/m2/hr. Can be indirectly measured by monitoring
oxygen consumption per unit time. [averages ~2000 kcal/day
Influences
Surface area – greater surface area, higher BMR
Age – younger, higher
Gender – Male much higher
Body Temperature – higher, higher
Stress – increases BMR
T3 and T4 – increase BMR
BODY HEAT & THERMOREGULATION
Imbalances
Hyperthermia – elevated body temperature - Heat stroke, fever
Hypothermia - too low --> death
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Body temperature
Core temperature =~ 37.2 - 37.6 oC [can be higher with high activity]
Shell temperature =~ 36.6 - 37.0 oC [can be higher with high activity]
Heat production & loss
Mechanisms of Heat Exchange
Radiation - exposed surface area [60%] - heat moves from high to low
Conduction - transfer to another object [ice pack, e.g.] [18%]
Convection - transfer by moving currents - water, air, etc.
Evaporation - sweat, etc. [22%]
Thermoregulation
Thermostat = hypothalamus [preoptic area]
Heat losing center - parasympathetic
Heat promoting area - sympathetic
Factors Affecting heat Production
Vasoconstriction, shivering,
Increase in metabolic rate
Hormones [T3, T4]
ALCOHOLISM - review system effects - p. 1029
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