Digestion, Absorption, and Metabolism

digestion

macromolecules into absorbable units; breaking down

absorption

mostly takes place in the small intestine; moving across cell membrane

water and ions in the large intestine

motility and secretion

digestion/absorption are influenced primarily by ___ in the GI

monosaccharides (glucose/galactose/fructose)

carbs can only be absorbed as ___

amylase

breaks down larger carbs into smaller glucose chains and disaccharides

brush border enzymes

on the microvilli on gut enterocytes apical side, target already digested carbs (disaccharidases) and breaks them further into monosaccharides

Na/K ATPase on basolateral side: provides Na/K gradient

GLUT 2: found on basolateral side

SGLT1: found on apical side

GLUT5: found on apical side

where are the 4 main transporters (Na/K ATPase, SGLT1, GLUT5, GLUT2) on gut enterocytes (in the mucosa layer) involved in carb absorption found within the cell?

SGLT1

secondary activate transporter symporter that uses existing Na gradient to bring glucose/galactose into cell (with higher affinity for glucose); on apical side of enterocytes, main driver of glucose entering cells

regulated by glucose in the intestine; increased glucose in lumen = increased expression of this

even if you have little glucose in the lumen or an equal amount as inside the cell, you can still transport it through the cell into the blood bc the Na gradient it follows is still present (and transport relies on that)

if you have low Na in the lumen, the driving force for glucose movement decreases so less is brought into the cell

if you have high glucose in the lumen, more will move into the cell bc it will follow its gradient

how will the activity of SGLT1/the movement of what it transports be altered in low glucose, low Na, and high glucose concentrations in the lumen?

GLUT5

facilitated diffusion (passive) of fructose; relies on concentration gradient

found on apical side

GLUT2

transport of all monosaccharides; found on basolateral side

glucose

most favorable monosaccharide for energy conversion (primary energy source to initiate glycolysis); taken into body from diet and levels in blood are monitored closely

stored in liver, and other carb compounds are converted to it

if you add glucose, it causes more Na to be able to be moved into cells bc it increases activity of SGLT1 (co-transporter of glucose and Na) → as glucose increases extracellular the co-transport mechanism continuously moves Na+ inside the cell as well, so short-circuit current charge increases

if you increased glucose concentration in the lumen, how would you expect short-circuit current to change?

you get hydrated faster if the water you drink has glucose/electrolyte ions in it; water follows their concentration, so increasing their concentration in cells draws water into cells to hydrate you faster

however if you have too high of a concentration of glucose outside your cells, you will get dehydrated (ex. diarrhea) very quickly bc there won't be enough transported to cells and it will draw water/ISF out into the GIT lumen

what happens to hydration levels/water movement in the body at small and large increases of extracellular glucose/ions?

endopeptidases and exopeptidases

what are the two methods/agents of protein digestion?

endopeptidases (proteases)

attack peptide bonds to break up large peptides into smaller ones

secreted by stomach (pepsin), intestine, and mainly pancreases as inactive proenzymes

ex. pepsin, trypsin

exopeptidases

release single amino acids into GI lumen by breaking terminal peptide bonds; secreted by pancreas

ex. carboxypeptidase

amino acids: secondary active transport

di/tri peptides: tertiary active transport (PepT1)

large peptides: transcytosis

what are the ways/structures proteins can be absorbed, and what is the mechanism for each?

primary active transport = Na/K ATPase → establishes Na gradient (bottom middle)

secondary active transport = Na/H+ exchanger and Na/AA cotransporter → use Na gradient from ATPase to move H+ out of cell or AAs into cell

tertiary active transport = PepT1 → uses H+ gradient from secondary Na/H exchanger to move dipeptides and tripeptides into cell

what is the primary, secondary, and tertiary active transport involved in protein absorption?

amino acid/Na co-transporter

follows existing Na gradient (from Na/K ATPase) to move AAs into cells (along with Na) into gut enterocytes

secondary active transport

PepT1

tertiary active transport following H+ gradient (established by H+/Na+ antiporter) that moves dipeptides and tripeptides into gut enterocytes

sometimes (less frequently) large peptides can come in via transcytosis

may elicit allergic response (if a foreign protein is absorbed)

more in infants with less developed digestive system; proteins in mother's breastmilk can be absorbed by child (passive immunity)

how are larger peptides brought into cells?

in this disease, the Na/AA secondary transporter is not functioning 

having PepT1 still working means that you can still have transport of di/tri peptides so they are not AA deficient 

having Na/K ATPase is also important for this, but not the main reason (to answer the question)

answer the question and provide reasoning for your answer choice

emulsification (bile salts)

process of breaking down large lipid droplets (fats) into smaller ones; physical/mechanical break down

increases SA for lipase action

bile salts

amphipathic agents; have one hydrophobic (interact with lipids) and one hydrophilic (interact with water) side

enzymatic fat digestion

lipase and colipase (helps anchor lipase so it can do its job, not involved in chem rxn) digest triglycerides into monoglycerides and free fatty acids; chemical breakdown

bile is from the liver, but these enzymes come from the pancreas

phospholipase digests phospholipids

micelle

form that digested fat from lumen exist in, which is a structure where digested fat (monoglycerides and fatty acids) is enclosed by bile salts; prevents digested fat from clumping together (which would be unable to enter cells), so they must be dissolved by bile salt

break down and reform constantly, and break down allows them to be absorbed; when they dissociate fatty acids/monoglycerides can cross the cell (into interior enterocyte)

emulsification, enzymatic fat digestion, and micelle formation

what are the 3 steps in fat digestion?

enter apical membrane: monoglycerides and fatty acids (when moved out of micelle) can diffuse into cell through membrane bc they are also hydrophobic and small (compatible with phospholipid bilayer)

when they enter cells they become chylomicrons for transport

how do digested fats enter cells?

chylomicrons

largest lipoprotein synthesized inside SI enterocytes; monoglycerides and fatty acids recombine into triglycerides and bind with cholesterol to form these

when digested fat enters cell it's packaged and sent throughout the body in these via LYMPHATIC system (not blood bc they are too big for it!)

lacteal

end of lymphatic system that allows chylomicrons to enter and travel within lymph vessels

leave basolateral membrane via exocytosis to enter lacteal → eventually the lymph vessels become leaky (larger gaps between cells/pores) and chylomicrons can diffuse into vena cava and travel to liver

indirectly travels to liver since digested fat goes all around body

describe the process of chylomicrons leaving a cell and traveling through the body (including start and end point)

bc you need a concentration gradient for passive diffusion of fats into cell; converting free fatty acids/monoglycerides into chylomicrons lowers intracellular concentration of them so more can move into cells

why is forming and transporting chylomicrons important?

the hepatic portal system (blood), liver (which utilizes those products; most absorbed nutrients go to liver first)

***second exchange site at liver sinusoids

(chylomicrons) enter lacteal (lymphatic system), which goes all over the body bc they enter the vena cava eventually

products of carb/protein digestion are absorbed into ___, which connects directly to the ___

products of fat digestion enter ___

hepatic arteries come from aorta and provide oxygen/nutrients to liver

blood vessels that supply GIT bring it oxygen/nutrients, but also receive digested/absorbed nutrients (except fat) and bring them to the liver (capillaries surrounding GIT go right to the liver via hepatic portal veins)

hepatic veins come out of liver to deliver blood it has processed elsewhere

how does blood enter and leave the liver?

the liver produces clotting factors, so if it is damaged you will not have those proteins being created and thus will have longer clotting time 

bc bile salts will be compromised, you won’t be able to digest/absorb fat as much so weight loss is possible 

you will have jaundice because bilirubin will not be incorporated into bile (which is made by the liver), so it will accumulate elsewhere 

drainage issues in liver can cause fluid to accumulate in portal veins and the capillary beds that support them, leading to accumulation of fluid in peritoneal cavity

answer the question and provide reasoning for all answer options

cecum (where the large intestine begins/where the ileum leads into) → ascending/transverse/descending colon → sigmoid colon → rectum

describe the structures that make up the large intestine in order (from closest to small intestine to end)

tenia coli

3 bands of smooth muscle that the large intenstine shrinks into; contractions of these "puckers" it into pouch-like segments called haustra

unique feature of large intestine because it has this and not a longitudinal layer (for smooth muscle)

smooth muscle transitions to skeletal muscle (external anal sphincter) in the large intestine

relatively slow movement within it so bacteria has a lot of time to grow and process digested food

movement is mostly segmentation, but has some unique strong peristalsis (mass movement)

describe the movement that occurs in the large intestine

mass movement (large intestine)

unique strong peristalsis of the large intestine; rare (only happens 3-5 times a day, normally after you eat) which increases urge to use bathroom

glucose-6-phosphate

glucose comes into cells via transporters and based on a diffusion gradient (high out/low in = move into cell) → cells add a phosphate onto glucose to "trick" transporters into thinking intracellular glucose is constantly low so it keeps flowing in

to be used in glycolysis, glucose must be converted to ___? Explain why

(1) enter glycolysis to generate ATP and pyruvate or (2) be stored as glycogen

these processes occur in the cytoplasm

what are the two pathways glucose-6-phosphate may enter after it is converted to that form, and where do they occur?

no oxygen = gets converted to lactate (lactic acid) → causes fatigue and lowering of tissue pH (more acidic)

oxygen present = enter mitochondria → interact with pyruvate dehydrogenase complex (contains pyruvate dehydrogenase) → become acetyl CoA and enter citric acid cycle → generate ATP and electron donors for ETC (also to generate ATP)

what happens to pyruvate in an environment with or without oxygen?

pyruvate dehydrogenase

enzyme that converts pyruvate into Acetyl CoA

part of pyruvate dehydrogenase complex

glycogen

branched polymer of multiple glucose units; stored in skeletal muscle or the liver when blood glucose is high

glycogenesis

process that forms glycogen; glucose must have been in the form of glucose-6-phosphate to be stored as glycogen or enter this process

primary enzyme of this process is glycogen synthase

glycogenolysis

when blood glucose is no longer high and a carbohydrate meal is not consumed to replenish it, glycogen may be broken down into glucose through this process

glycogen phosphorylase

primary enzyme in breaking down glycogen to glucose-6-phosphate

glucose-6-phosphatase

enzyme that will remove the phosphate off of glucose and allow it to exit the cell

the liver does have it since its primary role is to regulate blood glucose; it must have it so glucose can be released into the blood and supply tissues with an energy source

***also present in kidneys

muscles do NOT have it since their primary role is to generate force through contraction, which requires energy; they need to use all the glucose-6-phosphate they release when they break down glycogen for their own glycolysis (to make their own ATP)

what parts of the body have and lack glucose-6-phosphatase?

gluconeogenesis

occurs during fasting state, liver using products of digestion to make glucose; process of generating glucose from a non-carbohydrate precursor (including amino acids, pyruvate, lactate, or glycerol)

1) amino acids: via deamination (removal of -NH3) and the cori cycle

***excess protein consumption may lead to fat deposition as amino acids are converted to glucose (may eventually be produced in excess and converted to fat stores)

2) pyruvate: before exiting the cytoplasm

3) lactate

4) glycerol: generated in glycolysis, important for formation of triglycerides

describe the four substrates that may be converted into glucose via gluconeogenesis

fed state (absorptive state)

following a eating meal when the products of digestion are being absorbed, used, and stored

NET anabolic pathway; small molecules building into larger molecules (ex. glucose/AA monomer → glycogen/protein polymer

***in food we eat, carbs (glucose) is very important → plasma glucose level is critical for body functions 

priority/majority usage = metabolism in tissues and brain; immediate energy production 

***brain supply is prioritized the most (has high affinity glucose transporters)

next priority usage = storage in glycogen (glycogenesis)

least priority usage = excess glucose excretion in urine and storage as fat (lipogenesis)

how is glucose used in the body (prioritized)

used to regulate blood glucose (liver) or power muscle contraction (glycogenolysis)

stored glucose in the liver (glycogen) lasts 3-4 hours and can be used elsewhere in the body, but stored glycogen in muscles is only used by the muscles themselves

a small bit can be stored in the kidney as well

how is glycogen used by the body?

broken down and absorbed as AAs, which are used in synthesis of new proteins, and with higher amounts can be used in gluconeogenesis

after we eat proteins, they are ___

fats are broken down and absorbed as chylomicrons → enter lacteal and eventually blood → on blood facing side of endothelial cells, lipoprotein lipase breaks down chylomicrons → free fatty acids are used for immediate energy production (in liver in beta oxidation or gluconeogenesis)

describe the path of fat absorption and usage of them after

lipoprotein lipase

on blood facing side of endothelial cells, dietary fats are absorbed as chylomicrons which are broken down by this enzyme into glycerol and free fatty acids for storage (fed state) or energy production (fasted state)

after breakdown, they can be transported into adipose tissue for storage as fat molecules

fasted state (posabsorptive)

once all nutrients from a meal have been digested, absorbed, and distributed to various cells

NET catabolic state

blood glucose drops bc storage is dipped into for energy

liver: glycogen stores broken down, beta oxidation, gluconeogenesis

adipose tissue: breaking down triglycerides into free fatty acids (beta oxidation)/glycerol

muscle: cori cycle, glucose sparing, muscle breakdown (of own proteins to produce AAs that can be used in gluconeogenesis (least preferred method))

brain: consumer that uses glucose and ketones for energy

what are the key organs in homeostasis of metabolism in fasted state, and what methods do they use to provide energy?

glycogen stores are broken down to glucose and provide energy to other places in the body (including brain)

glucose can enter systemic circulation bc the liver has glucose-6-phosphatase, which removes phosphate group so it can leave liver cells and enter blood (muscles do not have this so they can't break glycogen directly into glucose)

describe how the liver breaks down glycogen stores to provide energy

beta oxidation

free fatty acids may be converted back to acetyl CoA as a source of energy for the citric acid cycle through this process

only really occurs in prolonged fasting state (in the liver)

acetyl CoA

precursor for cholesterol (lipid steroid with ring structure) and source of energy for citric acid cycle

in fasted state, starts to break down triglycerides into FFAs and glycerol → glycerol can be used in gluconeogenesis, FFAs can go into beta oxidation/generate ketone bodies

normally adipose tissue has cell membrane enclosure (perilipin) so lipase can't get in, but the break down of that barrier (so lipids can be broken down) and activation of hormone sensitive lipase facilitates this

describe how adipose tissues can break down to provide energy

hormone sensitive lipase

ONLY in fasted state, breaks down (phosphorylates) fats when activated by hormones; breaks down stored fats (triglycerides) into free fatty acids and glycerol in the fasted state to provide energy when blood glucose is low/ATP is needed

inhibited in the presence of insulin

perilipin

protects the fat stores from hormone sensitive lipase; when broken down (phosphorylated), becomes leaky and allows active hormone sensitive lipase to get in and access stored fat (mobilize it)

lipase/colipase: in SI/from pancreas

lipoprotein lipase: to break down chylomicrons

hormone sensitive lipase in adipose tissue

what are the 3 main lipases used in the body?

cori cycle

glycogen in muscles can be broken down into glucose-6-phosphate which enters glycolysis to make pyruvate/lactate → brought to liver for gluconeogenesis (which makes new glucose that can be brought back to the muscles/other places in body)

happens bc there's no glucose-6-phosphatase in muscle (can't leave cell)

indirectly, cori cycle

directly, glycogenolysis

muscle can provide glucose ___ via the ___, but not ___ generate glucose via ___

glucose sparing

in muscles, using fatty acids from broken down adipose tissue as an energy source over glucose, but it takes a while

insulin

endocrine signal (hormone) from pancreatic beta cells that promotes energy usage and storage; dominant in fed state and without this glucose can NOT enter cells

stimulates glucose transport into cells/glucose oxidation (using glucose) and glycogen/fat/protein synthesis (glucose storage)

glucagon

endocrine signal (hormone) from pancreatic alpha cells that promotes energy release; dominant in fasted state

stimulates glycogenolysis (breaking down glycogen), gluconeogenesis, and ketogenesis

the ratio of insulin to glucagon

metabolism is primarily controlled by ___, and signals sent to cells in fed or fasted state

insulin: high glucose in blood and high AA level in blood (can afford to store nutrients bc there is excess)

***nutrients being absorbed have receptors on beta cells to stimulate insulin release, but there are also receptors for GIP, GLP1, and NTs from the parasympathetic NS (rest and digest in fed state)

glucagon: low plasma glucose but high AA in blood (gluconeogenesis triggered in fasted state, which is helped by higher level of AAs)

what signals stimulate insulin and glucagon secretion?

GIP and GLP-1

GLP-1 stimulates insulin secretion → when you have an agonist of this it causes an increased response to insulin

____ are secreted by SI in high glucose to stimulate pancreatic beta cells to secrete insulin

because you want insulin production in anticipation of glucose arrival; even before glucose increases in blood, the body is ready to receive this

prevents glucose level from spiking/fluctuating too much

why do we have lots of parallel pathways to secrete insulin?

parasympathetic, not sympathetic, activates insulin secretion

all other choices are correct

answer the question and explain your answer

GLUT4

glucose transporter in adipose and resting muscle cells; at rest contained in vesicles, but in insulin presence there is increased expression of this via exocytosis of them to insert it into membrane and allow glucose to move into the cell via facilitated diffusion

when we exercise, it also increases expression of this on membrane

lipogenesis

stimulated in adipose tissue in the presence of insulin by G3P; if ATP is abundant it signals we don't need to make more since it's not actively being used → in this fed state (high blood glucose, excess ATP) acetyl CoA is used to build fatty acids

this is why extra carbohydrates often lead to fat deposition

in liver glucose must be transported in/out constantly (both fed and fasted state) → expression of GLUT2 is constant (and indirectly controls this)

in fed state hexokinase is activated to maintain glucose gradient (trap it in cells in a diff form) and help keep it moving into the cell

in fasted state glucose gradient favors glucose leaving the cell (bc if you haven't eaten extracellular glucose is low)

describe how glucose transport is balanced in the liver (concentration gradients in the fed/fasted states)

type 1 diabetes

insulin deficiency; people with this have lower body mass because their bodies always think they are in a fasted state

symptoms include hyperglycemia, increased gluconeogenesis, lipolysis and ketogenesis, and protein breakdown

destruction of pancreatic beta cells, genetic defect in MHC on chromosome 6

lipolysis

fatty acids may be released from fat stores through this process

ketogenesis

conversion of fatty acids to ketone bodies as an alternate energy source for the brain (which relies only on glucose and ketones for its high energy demands

occurs in times of starvation when we have very low available glucose

type 2 diabetes

insulin resistance; cells cannot respond to the insulin in the body

genetic defects in glucokinase, insulin molecule, insulin receptor, GLUT 4

***your body interprets this as fasted state even though you just ate because you can’t move glucose into cells without insulin

protein degradation occurs bc its a catabolic state 

NOT fat synthesis bc that’s an anabolic process

gluconeogenesis bc glucose is not entering cells (no insulin), and low insulin to glucagon ratio = like fasted state → causes more gluconeogenesis bc that’s what the hormone signal is saying 

NOT increase glycolysis because you’re not able to use the glucose you have 

***everything in the green box will happen, everything in the red will NOT 

answer the question and provide reasoning for all answer options

normal: in control conditions (Na and glucose present), glucose will be transported out of the intestinal sac into the exterior solution via SGLT1 (apical), so concentration in the sac would decrease. this would also happen exactly the same way in the cold condition, but just at a slower rate so concentration would not drop as much. however, without an Na gradient (in the low Na+ condition AND DNP condition since you need ATP for transport that creates the Na gradient) glucose will not be able to move out of the intestinal sac since SGLT1 relies on an Na gradient for secondary active transport, so the DNP and low Na+ concentrations would be the same as the initial concentration.

everted: for the same exact reasons, the same processes as described above would occur. however, the control and cold would increase instead (with cold rising less) because the lumen is facing the external solution (so glucose would go into

you have two sections of the small intestine tied at the ends suspended in two beakers, and inside both the intestinal sacs and beakers there is a 15mM glucose solution. in one beaker, the SI is inside out and the lumen side faces out ("everted"), and in the other it is oriented normally.

you have 4 experimental conditions (to alter the solution) for incubation: control (conditions as is), cold temperature, DNP (compound that disrupts ATP generation), and low Na+

describe how the concentration of glucose (mM) in the intestinal sac would change in each of these experimental conditions for the normal and everted setups