SALADIN C. 26

Nutrition & Metabolism,

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 appetite control

• Short term regulators– Ghrelin – from stomach – sensation of

hunger + stimulates hypothalamus to release

– GHRH

Appetite

– 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

Appetite

• 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

Appetite

• 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

Control of Feeding & Satiety

Figure 24.23

Appetite

• Neurotransmitters influence types of food consumed – Norepinephrine – CBH

– Galanin – fat

– Endorphins - protein

Appetite

• 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.

Heat – kinetic energy

• Heat = kinetic energy

• calorie-amount of heat required to raise one gram of H2O 1oC

Energy Yields

• Carbohydrates - 4Kcal/g

• Lipid- 9 Kcal/g

• Protein – 4 Kcal/g

Nutrients

• Nutrient – a substance that promotes normal growth, maintenance, and repair.

• Major nutrients – carbohydrates, lipids, and proteins.

• Other nutrients – vitamins and minerals (and technically speaking, water).

Nutrition – [see www.mypyramid.gov for details]

Figure 24.1

CBH

Fates of CBH’s • ATP production – aerobic respiration,

anaerobic fermentation

• Glycogen & adipose storage

• Amino Acid synthesis

• Structural component of nucleotides, glycoproteins, glycolipids

CBH

• 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

CBH

• Promotes intestinal function. Water soluble forms reduce blood cholesterol & LDL’s.

• Blood sugar levels – 70 -110 mg/dL = normal

Lipids

• Fatty acids, glycerol, cholesterol

• Meet 80 – 90% of resting energy needs

• Required for absorption of fat soluble vitamins

• Membrane & hormone structural components.

Lipids

• 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.

Lipids

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

Lipids

• Cholesterol & Lipoproteins - transported as spheres

• The spheres are lipoproteins – hydrophobic triglycerides & cholesterol esters are in interior, hydrophilic phospholipid heads, cholesterol & proteins are on exterior

Lipids

Classes• Chylomicrons – 2% protein, 90%

triglyceride, 3% phospholipid, 5% cholesterol

• VLDL – 8% protein, 55% triglycerides, 17% phospholipid, 20% cholesterol

Lipids

• 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]

Lipids

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

Lipids

• Bad– LDL > 159 mg/dL

– Total > 239 mg/dL

Lipids

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]

ProteinsProteins amino acids • 8 essential amino acids - we don't or

can't make enough

• 12 non-essential - synthesized by the body by transamination.

• Not stored – must be present from ingestion.

• Nitrogen balance –in = out – positive with growth, negative with insufficiency.

Vitamins & Mnerals

• 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

Metabolism

• Metabolism – all chemical reactions necessary to maintain life.

• Anabolic reactions – synthesis of larger molecules from smaller ones.

• Catabolic reactions – hydrolysis of complex structures into simpler ones.

CBH Metabolism

• All oxidative CBH consumption is essentially glucose catabolism

C6H12O6 + 6O2 6H2O +6CO2 + ATP [+heat]

• Glucose catabolism – glycolysis, anaerobic fermentation, aerobic respiration

Oxidation-Reduction (Redox) Reactions• Oxidation removes electrons.

• Reduction adds electrons.

• Coenzymes act as hydrogen (or electron pair) acceptors.

• Two important coenzymes are nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD).

Carbohydrate Metabolism

• Glucose is catabolized in three pathways:

– Glycolysis & anaerobic fermentation

– Krebs cycle

– The electron transport chain & oxidative phosphorylation

Carbohydrate Catabolism

Figure 24.5

Glycolysis

• A three-phase pathway in which:

– Glucose is oxidized into pyruvic acid.

– NAD+ is reduced to NADH + H+.

– ATP is synthesized by substrate-level phosphorylation.

Glycolysis

• 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+

Glycolysis

Anaerobic fermentation

• Glucose Metabolism in the Absence of O2

• 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+

• Runs twice per original glucose 2 Acetyl CoA’s

Matrix Reactions

• 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

Figure 24.7

Membrane Reactions

• Membrane reactions - oxidize NADH & FADH2 to move electrons, & regenerate NAD+ & FAD+

• Electron Transport System – on inner mitochondrial membrane – cristae - pumps H+ ions for Chemiosmosis.

Membrane Reactions

• 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.

Electronic Energy Gradient

Figure 24.9

Membrane Reactions

3 pumps present• 1 – NADH dehydrogenase complex –

FMN & 5 Fe-S centers – start – NADH + H+ is oxidized to NAD+ and FMN is reduced to FMNH2. Ends with Coenzyme Q – a mobile carrier that transports the electrons it receives to the next pump.

Membrane Reactions

• 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 & passes them o Cu then to cyt a, cyt a3 & then to O. The negative O picks up 2 H+ H2O [only place in respiration where O is consumed!!!]

Chemiosmosis

• Energy from step-wise release powers pumping H+ into intermembrane 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).

Chemiosmosis

– 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.

•  

Figure 24.8

Energy Yield of Cellular Respiration

Step Product Energy (O) Energy (no O)

Glycolsis 2 ATP 2ATP2ATP

2 NADH 4-6ATPTransition 2NADH 6ATPKrebs 2ATP 2ATP

6NADH 18ATP

2FADH2 4ATP

Totals 36-38ATP 2ATP

Glycogen Metabolism

Gluconeogenesis• Forms glucose from non-CBH molecules.

• In the liver.

• Protects the body, especially the brain, from the damaging effects of hypoglycemia by ensuring ATP synthesis can continue.

• Stimulated by insulin

Glycogen Metabolism

• Glycogenolysis – breakdown of glycogen in response to low blood glucose

• Stimulated by glucagon

Figure 24.12

Glycogen Metabolism

GlycogenesisGlucose is converted to Glucose – 6 – P

Glucose –6 – P is converted to glucose -1-P which is converted to glycogen

Liver Disorders

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

Hepatitis C

Lipid Metabolism

Lipid transport• Most non-polar lipids complex with

protein to produce water soluble spheres

Lipogenesis

• Excess glycerol & fatty acids undergo lipogenesis to form triglycerides in the liver.

• 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

Lipid Catabolism

Lipolysis• Lipids are split into glycerol & fatty

acids.

• Fatty acids undergo beta oxidation which produces 2-carbon acetic acid fragments, that can enter the Krebs cycle, or form ketone bodies

Lipid Metabolism

Figure 24.13

Protein Metabolism

• Excess protein results in amino acids being used to make other proteins, glucose, triglycerides or ATP.

• Proteins are not stored.

Protein Catabolism

Use as fuel:• Deaminated amino acids can be

converted into pyruvic acid & into one of the keto acid intermediates of the Krebs cycle.

ProteinsTransamination, 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

• Stimulated by GH, Insulin, T3, T4, estrogen and testosterone

Summary: Carbohydrate Metabolic Reactions

Table 24.2.1

Summary: Lipid and Protein Metabolic Reactions

Table 24.2.2

Absorptive and Postabsorptive States• Metabolic controls balance

blood concentrations of nutrients between two states:– Absorptive

•The time during & shortly after nutrient intake

Absorptive and Postabsorptive States

– Postabsorptive•The time when the GI tract is empty.

•Energy sources are supplied by the breakdown of body reserves.

Absorptive State

• Ingested nutrients enter blood and lymphatic system --> hepatic portal system to liver

• Lasts about 4 hours after completing a meal

Absorptive State

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%)

Absorptive State

Events:• 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]

Absorptive State

Figure 24.18a

Principal Pathways of the Absorptive State

Figure 24.18b

Postabsorptive State

• Need to maintain normal blood glucose level [90-100mg/100mL]

• Very important for nervous system - can only use glucose for energy.

Postabsorptive State

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

Postabsorptive State

• Muscle protein aa converted by liver into glucose [gluconeogenesis]

• Hormone – glucagon; Neural Control – ANS via epinephrine

Postabsorptive State

Figure 24.20a

Principle Pathways in the Postabsorptive State

Figure 24.20b

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]

Factors that Influence BMR

• Surface area, age, gender, stress, & hormones.

• Ratio of surface area to volume [if increases, BMR increases].

• Sex. [Males have a high BMR].

Factors that Influence BMR

• Stress. [Increases BMR].

• Thyroxine increases oxygen consumption, cellular respiration, & BMR.

Thermoregulation

Imbalances• Hyperthermia – elevated body

temperature - Heat stroke, fever

• Hypothermia - too low --> death

Thermoregulation

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]

Mechanisms of Heat Exchange

• The body uses four mechanisms of heat exchange:

– Radiation

– Conduction

– Convection

– Evaporation

Regulation of Body Temperature

Figure 24.25

Role of the Hypothalamus

• The chief thermoregulation center is the pre-optic region of the hypothalamus.

• Thermoregulatory areas include heat-loss & heat-promoting centers.

Heat-Promoting Mechanisms

• Activation of heat-promoting centers of the hypothalamus causes:

– Vasoconstriction of cutaneous blood vessels.

– Shivering.

– Increased metabolic rate.

– Enhanced thyroxine release.

Heat-Loss Mechanisms

• When core temperature rises, the heat-loss center is activated to cause:

– Vasodilation of cutaneous blood vessels,

– Enhanced sweating