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what are the two ways to get ATP
substrate level phosphorylation and oxidative phosphorylation
substrate level phosphorylation overview:
what does it do
how much ATP
slow or fast
what processes are included
driven by?
direct transfer of a phosphate group (ADP→ATP)
faster but produces less ATP
occurs in glycolysis and TCA
driven by delta G (energy)
oxidative phosphorylation overview
how much ATP
slow or fast
what processes are included
TCA cycle, ETC, and ATP synthase
slower, but more ATP generated
glycolysis important points
what is it
when does it occur
what does it require
two important enzymes
highly regulated step
glycose → pyruvate
occurs more rapidly when we need ATP from glucose
requires the input of ATP early on
hexokinase and glucokinase are important enzymes
PFK is the highly regulated step!!
whats the highly regulated step in glycolysis
PFK
what are the two most important enzymes in glycolysis?
hexokinase and glucokinase
2 regulatory mechanisms for glycolysis (broad)
hormonal or allosteric
hormonal regulation of glycolysis (2 things)
insulin and glucagon
allosteric regulation (negative and positive)
negative: reduce enzyme activity (ATP)
positive: increase enzyme activity (AMP)
PFK 1 (regulated by) vs PFK 2 (activated/inhibited by)
PFK 1: directly involved in glycolysis, regulated by AMP and ATP
PFK2: indirectly involved, activated by insulin (high glucose → more glycolysis), inhibited by glucagon (low glucose), produces a product that activated PFK1
pyruvate in aerobic conditions (where does it go & what does it undergo)
enters the mitochondria for oxidation
pyruvate in anaerobic conditions - what does it convert to? (during intense bout of exercise, RBCs, poorly oxygenated tissue)
pyruvate converts to lactate
pyruvate with oxygen normally
what does it become and where does it go
pyruvate → acetyl coA
enters TCA
enters oxidative phosphorylation (ETC and ATP synthase)
glycogenesis
whats formed
what stimulates it
what is the opposite :)
formation of glycogen in either the liver or muscle
stimulated by insulin (we need to store glucose) using branching enzymes
glycogenolysis is the complete opposite
when does glycogenolysis occur in the liver
between meals (raising BG)
when does glycogenolysis occur in the muscle
during activity, doesn’t affect BG levels
overview of gluconeogenesis
forming glucose from non carb sources (triggered by low BG and high glucagon)
occurs during overnight fasting
occurs in the liver but in kidneys if in starvation
what 3 substrates are involved in gluconeogenesis
amino acids, lactate, and glycerol
what relies on gluconeogenesis
RBCs, brain, and other CNS tissues
timeline of glycogenolysis and gluconeogenesis (in relation to BG): include before breakfast, after a meal, between meals, and overnight
before breakfast: gluconeogenesis
after a meal: BG directly from glucose
in between meals: glycogenolysis (liver)'
overnight: gluconeogenesis
pentose phosphate pathway
pathway when glucose is readily available
what are the two important products produced by the pentose phosphate pathway
ribulose-5-phosphate (1) and NADPH (2)
disrupted glucose and insulin signaling in T2DM (which 2 pathways does this affect and how)
unable to activate glycogenesis (unable to use glucose) and unable to turn off liver gluconeogenesis (release glucose)
what causes insulin resistance in organs
ectopic fat accumulation (fat stored in organs like the liver and muscle)
where is fat more favorably stored
subcutaneous fat (below the skin)
oxidative phosphorylation sequence
macronutrient digestion and absorption
TCA cycle
ETC
ATP synthase
TCA cycle starting product
acetyl coA (from pyruvate from glycolysis)
whats the purpose of the TCA cycle
creating high energy electrons
products of one TCA cycle
3 NADH
1 FADH2
1 ATP
Co2
what are the regulators of the TCA cycle (positive & negative)
positive (when energy is low): AMP or ADP
negative (when energy is high): end products of certain reactions (accumulation) and end products of the TCA cycle (NADH and ATP)
where does the ETC occur
the inner membrane of the mitochondria
purpose of ETC
e- are extracted from NADH and FADH, energy is released and forms a proton gradient (1, 3, and 4 generate protons)
what happens after e- go through the ETC
h+ flow down the concentration gradient through ATP synthase producing ATP
G cell role in digestion (2)
secrete gastrin to stimulate parietal and chief cells
what pathways occur in low energy status/low BG
glycolysis (oxidation of glucose to pyruvate)
glycogenolysis (breakdown of glycogen)
gluconeogenesis (creating glucose from non carbs)
what pathways occur with good energy status
glycogenesis (produce glycogen)
lipid synthesis (for later :))
key role of the cell membrane
receptors sensitive to external stimuli and channels that regulate movement throughout the cell
key role of the cytoplasm
provides support and controls movement of organelles and connects cellular components with microtubules
key role of the nucleus and what does it contain
“chief executive officer”
contains DNA (instructions)
key role of the mitochondria
produce the most ATP used by cells (why its the powerhouse)
key roles of the oral cavity (3)
teeth: mastication
salivary glands: lubrication
swallowing
key role of the esophagus and two structures within
transportation
UES opens during swallowing - bolus slides to the stomach
LES allows food to enter the stomach - cannot return, prevents reflux (GERD)
key role of the stomach
digestion & passing food into small intestine
regulation of gastric secretions
mechanical: grinding food
chemical: gastric juice (producing chyme)
secretions of the stomach and their functions
Mucus & bicarbonate – neutralize HCl along tissue wall (protects mucosa)
HCl – protein denaturation
Intrinsic factor – binds vitamin B12 and carries to ileum for absorption
Gastric lipase – hydrolyzes triglycerides (mostly short and medium chain)
Pepsinogen – first converted to pepsin
Pepsin is an endopeptidase – direct digestion of protein within the protein chain
Gastrin – stimulates parietal and chief cells to release HCl and pepsinogen, respectively
key roles, portions, and cells (1) of the small intestine
main site for nutrient digestion and absorption
duodenum, jejunum (most), ileum
enterocytes (absorptive cells of the SI) turn over every 3-5 days
4 processes of absorption in the small intestine
diffusion – substances freely cross membrane
facilitated diffusion – requires a carrier
active transport – requires a carrier and ATP
pinocytosis – engulfed by cell membrane a released on the inside of the cell
key roles of the large intestine
ascending, transverse, and descending
transportation and absorption
secretion of mucus (lubricant and protectant from bacteria) and bicarbonate (neutralize acids)
movement of material
key role of the pancreas
insulin and glucagon production
key roles of the liver
energy metabolism
produces bile to aid in digestion
emulsification of dietary lipids
Brings fats into liquid suspension
enzymes better able to break down lipids
solubilization of lipid digestion products for absorption
bile is a critical component of micelles – spherical structure that facilitates lipid absorption
key roles of the gallbladder
stores bile
CCK stimulates contraction and bile release
TCA cycle
location
what is metabolized
products
main goal
in the mitochondria (after molecules become acetyl coA)
carbohydrates, fatty acids, and amino acids metabolized
products from one cycle: 3 NADH (3 ATP later), 1 FADH2 (2 ATP later), 1 ATP, CO2 = 12 ATP total
produces a lot of electron carriers to make ATP later on
positive and negative regulators of the TCA cycle
positive: AMP or ADP (low energy)
negative: end products of certain reactions (citrate inhibits citrate synthase) or end products of the TCA cycle (NADH, ATP)
electron transport chain
where it occurs
what needs to happen before
end goal
occurs in the mitochondria (inner membrane)
occurs after TCA cycle (because we have electron carriers NADH and FADH2)
we need to extract the electrons and transfer to form a proton (H+) gradient
40% of energy is for ATP synthesis and 60% is heat
at the end, electrons are transferred to oxygen (producing H2O)
ETC complex 1
enzyme
what it contains
end goal
NADH coenzyme Q oxidoreductase
contains several Fe-S clusters
accepts e- from NADH, leaks some e- generating free radicals
ETC complex 2
enzyme
what it does
what it contains
fun fact
succinate dehydrogenase
accepts e- from FADH2
contains Fe-S cluster
the only complex that isn’t a H+ pump
coenzyme Q
what is it
what does it do
lipid soluble molecule that diffuses within the lipid bilayer
transfers e- from complexes 1 and 2 to complex 3
ETC complex 3
enzyme
what does it contain
coenzyme Q cytochrome c oxidoreductase
contains 3 cytochromes and an Fe-S protein
cytochrome c
what does it do
transfers e- from complex 3 to complex 4 within the inter-membrane
complex 9
enzyme
what does it contain
function
cytochrome c oxidase
contains Fe and Cu dependent proteins
transfers e- from cytochrome c to oxygen producing H2O
after TCA cycle and ETC, what happens?
H+ flow down concentration gradient through ATP synthase
for every pair of e- through the complex, 3 ATP are generated
CHO digestion pathway
oral cavity → stomach → SI
what occurs during CHO digestion in the oral cavity
digests polysaccharides (starches) using salivary alpha amylase
disaccharides are not digested here
what occurs during CHO digestion in the stomach
starch: small amount of digestion via alpha amylase until inactivated
disaccharides are not digested here
what occurs during CHO digestion in the SI
duodenum and jejunum starch digestion via amylase
at the brush border, remaining things are hydrolyzed and glucose is absorbed
at the brush border, disaccharides are digested producing lactase, sucrase, maltase, trehalase
which of the following organelles are involved in protein synthesis and export? nucleus, smooth ER, rough ER, golgi apparatus
nucleus, rough ER, golgi apparatus
Allosteric enzyme regulation involves directly blocking the enzyme “active site.” T/F
False
Insulin binding the insulin receptor is an example of….
Signals leading to a distinct event within the cell
2nd messenger signaling
External stimuli
external stimuli
T or F: Taking a creatine supplement should improve marathon running by significantly contributing to ATP supply during the course of the race
False
Which of the following best describes the end result of the TCA cycle?
Generates large amounts of ATP to be used for energy
Generates large amounts of NADH and FADH2 to be used as energy
Generates large amounts of NADH and FADH2 to be used as electron carriers
Generates large amounts of NADH and FADH2 to be used as electron carriers
T or F: NADH and FADH2 transfer their e- to the same ETC complex
false
Which stomach glands are most directly related to protein digestion?
cardiac
oxyntic
pyloric
oxyntic
Most macronutrient absorption takes place in the ileum T/F
false
The PFK step in glycolysis is regulated by which of the following (select all that apply)?
Protein Kinase A
Glucagon
AMP
Fructose 2,6 bisphosphate
Insulin
ATP
glucagon, AMP, fructose 2,6 bisphosphate, insulin, ATP
Lactate is a waste product of intense exercise. T/F
false
The principal issue with all glycogen storage diseases is that the brain has an inadequate supply of glucose. T/F
false
what are the three monosaccharides
fructose glucose, galactose
T/F To the best of our current knowledge, the negative effects of HFCS are because it increases calorie intake.
true
the principal reason dietary fiber has a lower caloric value than starch is…
Humans don’t have enzymes to digest the β-glycosidic bonds between monosaccharides within fiber
Fiber has a faster gastric transit time and therefore is not well absorbed
Fiber is a heteropolymer of monosaccharides, making it harder to digest
Humans don’t have enzymes to digest the β-glycosidic bonds between monosaccharides within fiber
At Thanksgiving, you eat so much turkey that the only other thing you eat is 0.5 slices of pie. The sugar from that pie will be absorbed by….
GLUT4
SGLT1
GLUT2
Amino acid receptors
SGLT1
Which of the following best describes beta cell failure?
Early in type 2 diabetes, the pancreas secretes very little insulin
Later in type 2 diabetes, the pancreas secretes a large amount of insulin
Later in type 2 diabetes, the pancreas secretes very little insulin
Early in type 2 diabetes, the pancreas secretes a large amount of insulin
Later in type 2 diabetes, the pancreas secretes very little insulin
T/F One must have obesity to develop type 2 diabetes.
false
What biomarker of glucose homeostasis would be best for monitoring the efficacy of a long-term (6 month) lifestyle intervention in people with type 2 diabetes?
A1c
Which of the following is NOT characterized by insulin resistance?
PCOS
Type 2 diabetes
Type 1 diabetes
T1D
T/F there is one cause of lactose intolerance
false
Which of the following can enter the gluconeogenic pathway? (select all that apply)
Acetyl CoA
Fatty acids
Lactate
Amino Acids
Glycerol
lactate, amino acids, glycerol
Which of the following are physiological actions of glucagon? (select all that apply)
Promoting glucose uptake by skeletal muscle
Promoting glucose uptake by adipose
Activating glycogenesis
Activating glycogenolysis
Activating gluconeogenesis
activating glycogenolysis and activating gluconeogenesis
Between breakfast and lunch, which pathway supplies glucose to prevent hypoglycemia?
glycogenolysis
T/F When consumed in excess (positive energy balance), fructose contributes more to liver fat than glucose.
true
Avoiding dietary CHO at all costs could lead to which of these unfavorable effects (select all that apply)
Avoiding many foods high in fiber
Increasing many foods high in fiber
Increasing saturated fat intake
Avoiding many foods high in fiber
Increasing saturated fat intake
T/F Overfeeding CHO and fat to the same degree induces similar weight gain.
true
Select all that are true.
Non-celiac gluten sensitivity appears to be a real condition
Non-celiac gluten sensitivity is present in 25% of the population
There are good biomarkers for non-celiac gluten sensitivity
Symptoms associated with non-celiac gluten sensitivity are definitely due to gluten (not another component of wheat)
non-celiac gluten sensitivity appears to be a real condition
pancreas digestion secretions:
acinar cells: digestive enzymes
duct cells: bicarbonate
pancreatic juice secretions contain:
Electrolytes (Na+, K+, Cl-)
Enzymes that act on all three energy nutrients:
Carbohydrases → hydrolyze carbohydrates (~50%)
Lipases → hydrolyze lipids (~90%)
Proteases → hydrolyze proteins (~50%)
Bicarbonate: neutralizes the acidic chyme arriving in the small intestine from the stomach
cell membrane structure
sheet-like composed primarily of lipids and proteins
mostly phospholipid (PL), also cholesterol – regulates membrane fluidity
carbohydrate chains are often attached to membrane proteins
its dynamic (fluid mosaic model: lateral diffusion, proteins dispersed)
What mechanisms occur in the cytoplasm
glycolysis, glycogenesis, glycogenolysis, pentose phosphate pathway, fatty acid synthesis
what is the largest organelle
nucleas
what is embedded within the mitochondria
the ETC
what are cristae
protrusions that increase surface area of mitochondria - more room for proteins (important for metabolism)
what the general structure of the mitochondria
outer membrane (relatively porous) & inner membrane (selectively permeable)
where does lipid and carb digestion begin
the oral cavity through digestive enzymes
where does protein digestion begin
the stomach