Lecture Nutrition & Metabolism PART 2

• When dietary protien is in excess, amino acids are
• -oxidized for energy
• -converted into fat for storage

• First deaminated (NH2 amine group removed) then converted into:
• -pyruvic acid
• -a keto acid intermediate of the Krebs cycle

• Events include:
• 1. transamination
• 2. oxidative deamination
• 3. Keto acid  modification
• 

Its hormonally controlled

it requires a complete set of amino acids that must be provided in the diet

• a dynamic state in which
• -organic molecules (except DNA) are continuously broken down and rebuilt
• -organs have different fuel preferences

3 interconvertible pools

• -amino acids
• -carbohydrates
• -fats

Body's total supply of free amino acids

• source for:
• -resynthesizing body protiens
• -forming amino acid derivatives
• -gluconeogensis

easily interconverted through key intermediates

• differ from amino acid pool in that:
• 1. fats and carbs are oxidized directly to produce energy
• 2. excess carbs and fat and can be stored

• Absorptive (fed) state:
• -during and shortly after eating
• -absoption of nutrients is occuring
• -anabolism exceeds catabolism

• Postabsoptive (fasting) state:
• -when the GI tract is empty
• -energy sources are supplied by breakdown of reserves
• 

glucose is the major energy fuel

glucose is converted into glycogen or fat (by the liver)

lipoprotein lipase hydrolyzes lipids of chylomicrons in muscle and fat tissues

most glycerol and fatty acids are converted into triglycerides for storage

triglycerides are used by adipose tissue, liver, and skeletal and cardiac muscle as a primary energy course

excess amino acids are eaminated (to keto acids) abd ysed for ATP synthesis or stored as fat in the liver

most amino acids are used in protetin synthesis

1. Glycogenolysis in the liver metabolizes glucose quickly and efficiently

2. Glycogenolysis in skeletal muscle to pyruvic acid in the liver

• 3. lipolysis in adipose tissues and the liver
• -glycerol is used for gluconeogenesis in the liver

• 4. Catabolism of cellular protein during prolonged fasting
• -amino acids are deaminated and used for gluconeogensis in the liver and later in the kidneys (for fasting that lasts several weeks)
• 

glucagon release is stimulated by:

• -declining blood glucose (dampening insulin release)
• -rising amino acid levels

Glucagon is a hyperglycemic (sugar raising) hormone that promotes:

• -glycogenolysis and gluconeogenesis in the liver
• -liplysis in adipose tissue
• -modulation of glucose effects after a high-protein, low carb meal (a counter balance for glucose)
• 

• in response to low plasma glucose, or during the fight-or-flight response or exercise, the sympathetic nervous system and epinephrine from the adrenal medulla promote
• -fat mobilization
• -glycoenolysis

• Hepatocytes:
• -process nearly every class of nutrient
• -play a major role in regulating plasma cholesterol levels
• -store vitamins and minerals
• -metabolize alcohol, drugsm hormones, and bilirubin

*important dietary lipid

structural basis of bile salts, sterooid hormones, and vitamin D

major component of plasma membranes

makes up part of the hedgehod singaling molecule that directs embryonic development

transported in lipoprotein complexes containing triglycerides, phospholipids, cholesterol, and protein

• HDLs (high density lipoproteins)-have the highest protein content.  
• *Transport excess cholesteral from peripheal tissues ot the liver to be broken down and secreted into bile.
• *Also provide cholesteral to steroid-producing organs

• LDLs (low density lipoproteins)-cholesterol-rich
• transport cholesterol to peripheal tissues for membranes, storage, or hormone synthesis

• VLDLs (very low density lipoproteins)-mostly triglycerides
• transport triglycerides to peripheral tissues (mostly adipose)
• liver is the primary source of VLDLs

• Chylomicrons: transport absorbed lipids in GI tract and have the lowest density of all lipoproteins
• 

High levels of HDL are thought to protect against heart attack (good cholesterol) and a level of above 60 is desirable

High levels of LDL, esp lipoprotein A increase the risk of heart attack.  Alevel of below 100 is desireable

At a basal leel regardless of dietary intake (about 85%)

in reponse to saturated fatty acids

• Saturated fatty acids:
• stimluate liver synthesis of cholesteral
• inhibit cholesteral excretion from the body

• Unsaturatred fatty acids:
• enhance extcretion of cholesterl from body

• Trans Fat
• hardened by hydrogination (very bad!)
• increases LDLs and reduces HDLs

found in cold-water fish

lower the proportions of saturated fats and cholesterol

have an antiarrhythmic effect on the heart

help prevent spontaneous clotting

lower blood pressure

stress, cigarette smoking, and coffee lower HDL levels

Aerobic exercise and sestrogen increase HDl levels and decrease LDL levels

• body shape:
• -"Apple": fat carried on the upper body is correlated with high cholesterol and LDL levels. more common in men
• -"Pear": fat carried ont he hips and thighs is correlated with lower cholesterol and LDL levels. more common in women

Bond energy released from food must equal the total energy output

energy intake=the energy liberated during food oxidation

• energy output:
• -immediately lose as heat (~60%)
• -used to do work (driven by ATP)
• -stored as fat or glycogen

Eventually, nearly all energy derived from food is converted to heat!

it cannot be used to do work

it warms the tissues and the blood

helps maintain the homeostatic body temperature

allows matabolic reaction to occur efficiently

• Measured by the body mass index (BMI)
• 

• considered overweight if BMI is 25-30
• considered obese if BMI is over 30
• -higher incidence of atherosclerosis, diabetes mellitus, hypertension, heart disease, and osteroarthritis

• Two sets of distinct hypothalmic neurons
• 1. LHA neurons promote hunger when stimulated by neuropeptides (e.g. NPY)

2. VMN neurons cause satiety through release of CRH when stimulated by appetite-suppressing peptides (e.g. POMC and CART peptides)

• Factors that affect brain thermoreceptors and chemoreceptors:
• -neural signals from the digestive tract
• -bloodborne signals erlated to body energy stores
• -hormones
• -to a lesster exten, body temperature and psychological factors

• Neural signals:
• *high protein content of meal increases and prolongs afferent vagal signals
• *distenstion sends signals along the vagus nerve that suppress the hunger center

• Nutrient Signals:
• *increased nutrient levels in the blood depress eating
• *blood glucose
• *amino acids
• *fatty acids

• Hormones:
• *gut hormones (e.g. insulin and CCK) depress hunger
• *glucagon and epinephrine stimulate hunger
• *Ghrelin (Ghr) from the stomach stimulates appetite just before a meal ("dinner bell")

• Leptin: hormone secreted by adipose cells in reponse to increased body fat mass
• *indicator of total energy stores in the fat tissue (the fat-o-stat)
• *protects against weight loss in times of nutritional deprivation

Leptin acts on the ARC neurons in the hypothalamus

• If too much fat, it suppresses the secretion of NPY, a potent appetite stimulant and it sitmulates the expression of appetite suppressants like CART peptides
• 

• Temperature
• stress
• psychological factors
• adenovirus infetion
• sleep deprivation

Body's rate of energy output!

Total heat produced by chemical reactions and mechanical work of the body

meaured directlt with a calorimeter or indirectly with a respirometer (masures O₂ consumption that is in drect proportion to heat production)

Reflects the energy the body needs to perform its most essential activities, like breathing

this is measured under controlled confitions

• Factors influencing BMR:
• -as the ration of body surface are to volume increases, BMR increases
• -decreases with age (highest in children using energy to grow)
• -increases with temperature or stress
• -males have disproportionately higher BMR due to more muscle mass
• -thyroxine increases O2 consumption, cellular respiration, and BMR (the metabolic hormone produced by thyroid gland)

BMR is a large part of the TMR

rate of kilocalorie consumption to fuel all ongoing activities

increases with skeletal muscle activity and food ingestion

body temperature reflects the balance between heat production and heat loss

at rest: the liver, heart, brain, kidneys, and endocrine organs generate the most heat

during exercise: heat production from skeletal muscles increases dramatically

• normal body temp= 37C + - 5C (98.6F)
• (optimal enzyme activity occurs at this temperature)

• increased temperature denatures proteins and depresses neurons
• 

organs in teh core have the highest temperature

blood is the major agent of heat exchange between the core and the shell

core temperature is regulated and remains relatively constance, while the shell temp fluctuates substantially (20C-40C)

HEAT ALWAYS TRAVELS DOWN THE GRADIENT

• 1. Radiation (thermal energy)is the loss of heat in the form of infared rays.
• -accounts for about 1/2 of the body's heat loss in normal circumstances

2.  Conduction is the transfer of heat by direct contact

3. Convection is the transfer of heat to the surrounding air

4.  Evaporation is the heat loss due to evaporation of water from body surfaces

Insensible heat loss accompanies insensible water loss from lungs, oral mucosa, and skin (this is unnoticable)

evaporative heat loss becomes sensible (active) when body temperature ruses and sweating increases water vaporization

The hypothalamus is the main integrating center for thermoregulation!!

• Preoptic region og the hypothalamus contains the two thermoregulatory centers
• -heat-loss center
• -heat-promoting center

• the Hypothalamus receives afferent input from:
• -peripheal thermoreceptors int he skin
• -central thermoreceptors (some in hypothalamus)

initiates appropriate heat-loss or heat-promoting activities, acting must like a thermostat!

1. contriction of cutaneous blood vessels

2. shivering

3. increased metabolic rate via epinephrine and norepinephrine (nonshivering thermogensis provein in infants but controversial in adults)

4. enhances thyroxine release (in infants only)

• Voluntary measures include:
• -putting on more clothing
• -drinking hot fluids
• -changing posture or increasing physical activity
• 

Dilation of the cutaneous blood vessels

Enhanced sweating

• Voluntary measures include:
• -reduced activity and seeking a cooler enviornment
• -wearing light colored and loose fitting clothing
• 

elevated body temperature depresses the hypothalamus

positive feedback system (heat stroke) begins at a core temp of 41C

can be fatal if not corrected with ice bath and fluids

heat-associated collapse after vigorous exercise

due to dehydration and low blood pressure

heat-loss mechanisms are still functional

may progress to heat stroke

low body temperature where vital signs decrease

shivering stops at core temp of 30-32C

can progress to coma and deat by cardiac arrect at 21C

Fever is controlled hyperthermia

it can be due to infection (also cancer, allergies, or CNS injuries)

macrophages release interleuns (pyrogens) that cause the release of prostaglandins from the hypothalamus

prostaglandins rese thte hypothalamic thermostat higher (heat promoting mechanisms kick in, which is why you can still shiver with chills!)

natural body defenses or antibiotics reverse the diesease process; crygens reset the thermostat to a normal level

lack of proteins in utero and the first three years can lead to mental deficites and learning disorders

insulin-dependent diabetes mellitus and genetic disorders can lead to metabolic problems in children

non-insulin dependent diabetes mellitus may occur in middle and old age, especially in the obese

metabolic rate declines with age throughout the life span

nonenzymatic binding of glucose to proteins increases with age, leading to lens clouding and general tissue stiffening in elderly

Diuretics for heart failure and hypertension increase the risk of potassium loss

some antibiotics interfere with digestion and absorption and lead to dehydration by diarrhea

mineral oil (laxative) decreases absoprtion of fat-soluable vitamins

excessive alcohol consumption may lead to malabsorption, vitmain and mineral deficiencies, deranged metabolism, and damage to liver and pancreas