HHP 101 Topic 5: Cellular Metabolism and ATP Production; Nutrition, Energy, and Human Health

how do cells make energy?

we take in food in order to break down the chemical bonds and use the parts of the larger molecules to make energy

3 main pathways that allow cells to make energy

glycolysis, Krebs cycle, oxidative phosphorylation (ETC)

glycolysis

-cytoplasm of cell

-only carbohydrates are used

-can occur with or without oxygen (glycolysis doesn’t need oxygen)

process of glycolysis

-glucose is transformed into 2 phosphate, 6 carbon product that will be broken down into two 3 carbon products

-low ATP yield

what do we gain from glycolysis?

-4 ATP (net gain 2 ATP)

-2 pyruvate

-2 NADH (electron carriers)

presence of oxygen in glycolysis

-O2 present: pyruvate will continue to mitochondria for aerobic respiration

-no O2 present: pyruvate will become lactate through fermentation (produces no ATP)

citrate acid cycle

-acetyl CoA enters the cycle

-occurs in the mitochondrial matrix

products of the citric acid cycle (per each full turn of the cycle: 1 acetyl CoA)

-1 ATP

-2 CO2

-3 NADH

-1 FADH2

(if asked “per glucose” everything is doubled)

oxidative phosphorylation

-occurs in mitochondria

-provides the highest yield of ATP from glucose (includes ETC)

energy levels of electrons in ETC

every time an electron moves to a new protein it loses energy

types of transport used in oxidative phosphorylation

-active transport: pumping of H+ ions into the inter membrane compartment that sets up a gradient (instead of ATP powering, electron energy is used)

-facilitated diffusion: when space is full of ions, H+ ions are channeled back through to the other side (drives ATP synthase)

products of oxidative phosphorylation

-30-34 ATP per glucose

total net yield from cellular respiration

TOTAL: 34-38 ATP (per one glucose)

-2 ATP from glycolysis

-2 ATP from citric acid cycle

-30-34 from oxidative phosphorylation (+ ETC)

is maximum ATP always achieved?

NO

-NADH or FADH2 may be used in other processes, removing its contribution to ATP synthesis

-mitochondria may use some of the energy in the hydrogen electrochemical gradient for other purposes such as the uptake of pyruvate via symport

lipids for energy

-gives more ATP per molecule than carbs/proteins

-ONLY occurs in the MITOCHONDRIA and requires O2

-oxidizes a B-bond in fatty acids to convert energy into ATP

-consumes 2 ATP (one time event)

-bond of fatty acid is cleaved, creating 2 acetyl CoA molecules

reduction of carbons in lipid energy use

each round decreases C number by 2 (18C=9 rounds→9 Acetyl CoA)

what happens to the acetyl CoA formed from lipids?

goes into the citric acid cycle like normal

how much NADH and FADH2 are formed through lipid energy storage?

per B-oxidation… amount of reactions depends on length of the fatty acid chain

-1 NADH and 1 FADH2 (for each round)

-18C F.A.-8 rounds→8 NADH and 8 FADH2… 3 F.A. chains→24 NADH and 24 FADH2

ATP production from lipid energy

-from a single 18 carbon F.A…. net production of 146 molecules of ATP/1 F.A.

triglyceride ATP production from lipid storage

-each triglyceride stored in adipocytes has 3 F.A. (18 C each)

-yields 438 total ATP

-triglyceride storage for energy= most efficient form

proteins for energy production

-LAST RESORT

-5% of total energy production in body

-proteins broken into amino acids

-nitrogen must be removed

-products enter C.A.C. or glycolysis

methods of using proteins for energy

transamination, oxidative deamination

transamination

amino group transferred to a keto acid (most commonly goes to the C.A.C.)

-some of these new products can be made into glucose to enter glycolysis

oxidative deamination

amino group removed and forms NH3 (ammonia-toxic) converted to urea in the liver and excreted in urine

-less frequently seen

cells cannot function without ATP

-cells don’t have to work as hard when using glucose

-when using F.A…. cells have to go through processes first in order to be used

cells need energy to function

for animals, this energy (ATP) is found in the chemical bonds of consumed food substrates- these are the energy input

3 macronutrients

carbs, lipids, proteins

carbs

-4 kcals/gram

-preferred source for ATP production

-stored in liver as glycogen

-can be broken down into glucose is blood sugar is low

-can be stored in muscle as a local supply when energy production is necessary

proteins

-4 kcals/gram

-last resort for ATP production

-consume protein which is broken down into amino acids in the small intestine

-these building blocks are then used to generate new proteins in the cells

lipids

-9 kcals/gram

-most ATP but 2nd choice in ATP production

-diverse group

2 forms of expenditure (energy output)

external work, internal work

external work

energy expended when skeletal muscles contract to move objects, or the body

-not required to maintain life

-ex: exercise, walking around campus

internal work

all other forms not involved in mechanical work outside the body

-required to maintain life

-includes skeletal muscle activity used besides external work (shivering, posture, chewing), energy expended to sustain life (breathing, cardiac function, Na+/K+ pump, reactions of cellular repair and growth)

energy transfer

-energy that is not being used is stored (mostly in adipocytes)

-when energy is released from breakdown of chemical bonds in nutrients (not all can be used)

-during biochemical processing of food (1/3 of energy in food is captured by the body, other 2/3 of ene

metabolism

sum total of all chemical reactions in the body

-ex. ATP synthesis, DNA replication, mitosis, transcription/translation, cell repair

metabolic rate

the rate (measured of some unit/time) at which energy is expended during work (internal and external combined)

-metabolic rate = energy expenditure/unit of time (kCal/hr) (calories used/time)

basal metabolic rate (BMR)

metabolic activity needed to maintain basic bodily functions under resting conditions

-energy spent/time @ REST

BMR is accurately measured when…

-a person is at rest (no activity for 30 mins)

-mentally calm (no stress)

-comfortable room temperature (avoid shivering)

-fasted for at least 12 hours (prevents diet induced thermogenesis

measurement of BMR

-typically measured indirectly by quantifying O2 uptake over several hours

-direct calorimetry measures heat produces by the body while in chamber circulated by cool water

factors that affect metabolic rate

-thyroid hormone (direct response: increased thyroid→increased metabolic rate

-physical activity (during heavy exercise, metabolic rate can be increased by 16-20 fold)

body weight

-to maintain constant body weight, energy input must = energy output

-negative energy balance… energy input > energy output

-positive energy balance… energy input < energy output

energy in the body

-energy in food consumed= external work + internal work + heat produced + stored energy

-we should be able to alter body weight by changing caloric input and/or output

feedback regulation of energy

-works for a few weeks before metabolic resistance develops making further weight gain or loss more difficult

-change in food consumption offset by alteration in energy expenditure (negative feedback)

what is one of the most important factors in maintaining proper body weight?

controlling energy intake (also consider activity levels)

body mass index (BMI)

standard for determining if you are underweight

-calculates an estimate of healthy weight based on height, weight, and sex

-does not measure body fat directly

-most commonly used metric in cardiovascular research and research on weight trends

-flawed metric (athletes with increased muscle mass have inflated BMI)

underweight BMI

-less than 18.5 considered underweight

increased risks of underweight BMI

malnutrition, vitamin deficiencies, decreased immune function, increased risks or complications from surgery, fertility issues in females, growth and development issues for children and teens, fragile bones, fatigue, anemia

causes of an underweight BMI

family history, high metabolism, physical activity, physical illness or chronic disease, mental illness

overweight BMI

-11-19% greater than desirable (25-29)

-pears v. apples

-fit v. fat

obesity

identified when body weight is 20% (or more) higher than desirable/healthy body weight as suggested by USDA, or a BMI is greater than or equal to 30

-markedly greater health risk

morbidly obese

BMI is greater than or equal to 35

super obese

BMI is greater than or equal to 40

4 physiological factors that control obesity

-increased circulating glucocorticoids (stress hormones, cortisol)

-insulin resistance (type 2 diabetes)

-mutation of leptin receptor in the brain

-increased production of neuropeptide Y in hypothalamus

factors in obesity

-hypothalamus mainly in control of food intake

-different sets of neurons in hypothalamus release appetite (“hunger”) and satiety (“satisfaction”) signals

-neuropeptide Y acts as potent appetite signal, melanocortins act as a satiety signal

-release of both is affected by satiety/appetite signals produced by other parts of the body

leptin

-first appetite controlling hormone identified, it acts to decrease food intake and increase metabolic rate (also stimulates increased physical activity)

-increases production of melanocortin, decreasing food intake and signaling satiety

-as fat cells decrease in size, leptin production decreases, thus increasing appetite and decreasing metabolic rate

what is leptin produced and released by?

adipocytes

-as fat cells increase their glucose intake, release of leptin increases… in turn, leptin decreases production of neuropeptide Y and the appetite is reduced

insulin

-released into bloodstream by pancreas when blood levels of glucose increase to cause intake into the cells, high insulin levels also inhibit release of neuropeptide Y causing a decrease in appetite

-signals adipocytes to release leptin

what happens if insulin amounts are too high?

can cause desensitization of the cell receptors that respond to it (type 2 diabetes)

-decreased uptake of glucose from blood by the cells

-elevated blood glucose

-decreased energy (no glucose in the cell)

ghrelin

-”hunger hormone”

-produced by the stomach and released into blood before meals

-causes the production of neuropeptide Y in hypothalamus, stimulating appetite (low calorie diets= increased ghrelin production)

-ONLY one to SIGNAL increased NPY

digestive hormones (peripheral hormones)

leptin, insulin, PYY 3-36, CCK, ghrelin

leptin

-release point: adipocytes (in presence of insulin)

-action: 1. go to hypothalamus and decrease NPY (awareness of hunger) 2. increase melanocortin (increased satiety awareness)

insulin

-release point: pancreas, blood glucose increased

-action: 1. adipose→leptin 2. decrease NPY (decrease hunger)

PYY 3-36

-release point: small and large intestines

-action: increased satiety

CCK

-release point: small intestine

-action: increased satiety

ghrelin

-release point: stomach

-action: increased NPY (increased appetite)

food intake and other factors

stress, anxiety, depression, conditioning to certain times/places, socializing with others, taste and smell of food

number of Americans overweight or obese

2/3 of Americans

obesity prevalence rate in the US (2017-2020)

41.9%

obesity prevalence rate in the US (1999-2000)

30.5%

estimated annual medical costs for obesity in 2019

$173 billion

-medical costs for adults with obesity were over $1800 higher than those of a healthy weight

obesity and life expectancy

obesity can take 10 years off life expectancy, overweight can take 1 year from life expectancy

health risks of obesity

hypertension (increased BP), poor blood lipid profile (cholesterol), increased risk of gall stones (gallbladder removal), increased risk of osteoarthritis (increased stress on joints), increased risk of cancer, increased risk of heart disease, type 2 diabetes (insulin resistance), psychological strain (anxiety, depression, low self-esteem)

causes of being overweight or obese

lack of energy balance, inactive lifestyle, environment, family history/genetics, health concerns, medicines, emotional factors, quitting smoking, pregnancy, decreased sleep

physiological contributors to obesity

1. faulty leptin signaling pathway

2. decreased physical activity

3. differences in “non-exercise activity thermogenesis” (NEAT) (standing, sitting)

4. differences in extraction energy from food (genetic)

5. overfeeding during critical periods of life

6. number of fat cells influences appetite center

how do we treat obesity?

-traditionally, involve caloric restriction (diet)

-smaller, more frequent meals (less insulin released)

-exercise

why is diet alone not effective?

90% of obese people who lose weight by diet alone re-gain weight within 5 years (more coming back as fat)

surgery to treat obesity

gastroplasty, gastric bypass, gastric banding

gastroplasty

-“stomach stapling”

-reduces size of stomach so that person feels “full” easier

-remaining part of stomach can enlarge if eating behavior is not changed

-side effects: nausea, vomiting, diarrhea, vitamin deficiency

gastric bypass

-attach lower segment of small intestine to stomach so most food bypasses stomach and all intestine to reduce absorption

-side effects: nausea, vomiting, can’t drink fluids before 30 mins of eating (not enough space), need to consume extra vitamins

gastric banding

-places silicone rings or mesh band around stomach to reduce its size to feel “full” sooner

-side effects: nausea, vomiting, heart burn, slipping of band

success of gastric surgery

-moderate rate of success and many side effects

-only 30-50% of people having surgery actually experience significant amounts of weight loss and maintain new weight for at least 5 years following surgery

-90% of those having surgery experience side effects of chronic diarrhea, vomiting, nausea, heart burn, dehydration, nutritional deficiencies, and intolerance to dairy products

-should only be used in cases of morbid obesity

how can we improve the success of gastric surgery?

-create or make more available safe places for physical activity (parks, greenways)

-enhanced physical education programs and physical activity in schools

-street and community planning

fighting obesity (community level)

-increased supermarkets with FRESH food in low income areas

-increase distribution of local fruits and vegetables to schools, less processed food

-decrease the fat and sugar in the diet

-drink more water, less sugary drinks

-increase activity during the day