Tissue Specialization In Metabolism Flashcards
Major energy consuming activity of brain
Ion transportation to maintain membrane potential
Integration of different inputs
Sending signals
Major Energy activity of kidney
Filtration
Active transport
Primary fuels for brain
Well fed =
Glucose
Fasting = ketone bodies
No FFAs through blood brain barrier
Brain cannot store fueL!!!
Skeletal muscle fuels
Primary :
FAS, glucose, ketone bodies
Burst of exercise = phosphocreatine
High e molecule
Efficient at mobilization
Faster than glycogen
Refuels atp from adp = consistent atp concentration
Phosphocreatine structure reminders
4 carbons
3 nitrogens
Carboxyl on one head
Phosphorous on other
Naughty cars = gym bros = creatine = nitrogens and Carboxyl
Phosphorous head
Nh
cNh2
Nch3
Ch2
Carboxyl group
Acetone structure reminders
Most basic ketone
CH3-co-ch3
Ace = 1st = 1st ketone ever made
“Ace” = c butt = double bond is butt crack for 3 c ass
Acetoacetate structure reminders
Ketone bodies
4c ketone
Ketone group
Carboxyl group at end
Ass to ass Tate
= ass where double bond to o is butt crack
Tate = cars = Carboxyl
D-Beta-hydroxybutyrate structure reminders
4c alcohol with Carboxyl group at end
D-beta = low key alcoholic frat boy loser kind
Still rich enough so gets a car and spot in frat
Cardiac muscle/ smooth muscle fuels
Glucose, FAS, lactate
No storage abilities
Phosphocreatine = heart protection
Adipose tissue fuels
FAS, TAGs, ketone bodies
Energy for two months
Hormonally regulated
Main energy activity of liver
?
What enables the concentration of blood to be basically equal to that of hepatocytes?
GLUT2
Glucokinase function
Also known as hexokinase iv
Phosphorylates glucose to glucose 6 phosphate
Unique features of glucokinase
High km
= harder to over saturate l
When glucose is low, rate is low
Fate of amino acids in liver
Liver proteins
Aas in blood
Nucleotides, hormones, porphyrins
Nh3 - urea
Pyruvate==>
-glucose via gluconeogenesis
-acetyl coa
—FAs
—cac = glucose
—atp via cac
Muscle proteins degrade
To alanine and pyruvate
Fatty acid fates in liver
Liver lipids
Plasma lipo Proteins = ldl/ hdl
FFAs in blood
Oxidative fuel = nadh —> acetyl coa
-acetyl coa =>
—atp
—cholesterol = carried by lipo proteins
—-ketone bodies
Serum albumin
Most abundant plasma protein
1 molecules carries 7 FFAs
Liver function
Body’s distribution center
Correct proportions of nutrients
Nutrient storage = vitamin a, iron
Detox of xenobiotics
Carbohydrate fates in liver
Glucose 6 phosphate
-glycogen
-glucose
-ribose 5 phosphate = NADPH through PPP
——NADPH needed for FAS, cholesterol, ribose 5 phosphate, detox
-pyruvate
—acetyl coa
——cholesterol
——atp
How is hexokinase regulated?
Fructose 6 phosphate = product of phosphorylated glucose in liver = activates transport into nucleus = nuclear binding protein
Glucose activates transport out of nucleus
Brief Cori cycle overview
Glycogen in muscle -> lactate = produces atp for energy
Lactate transported to liver
Lactate -> glycogen = consumes atp
ATP in liver = CAC = oxidative phosphorylation = needs o2 = heavy breathing
White adipose tissue (WAT)
Amorphous
Widely distributed
Single big fat lipid droplet filled with TAGs, sterol esters
15% of adult human mass
What organ is primary source of FAs?
Liver
Adipocyte metabolism
Lots of carbs = TAGs stored in lipid droplet
Energy needed = FFAs into bloodstream
- 70% released restored as TAGs
Pyruvate to glycerol 6 phosphate via glyceroneogenesis
—> TAGs synthesis = cytosolic pep Carboxylase
Only tissues that have glycerol kinase can metabolize free glycerol
What tissues?
Liver, kidneys, BAT, lactating mammary gland
Brown adipose tissue (BAT)
Common in small mammals
Thermogenic
Mitochondria heavy, lots of small lipid droplets
More capillaries
Produces UCP1= uncoupling protein 1 = thermogenin
Activated by cold temperatures, dissipation of energy as heat
fasting + cold = brain, spine, collar bones, kidney, bladder light up
Just fasting = brain, heart, kidney, bladder
PET
Positron emission tomography
Shows glucose uptake by body
When body is injected with FDG = 2-f18-fluoro2-deoxygenated-D-glucose
= cannot be metabolized
= tracks radiation emitted by tracer
FDG structure reminders
Glucose ring
A bunch of OHs
But
F18 on carbon two to right of oxygen in ring
Where does formation of ketone bodies occur?
Liver mitochondria matrix
Generic pathway for ketogenesis
2 acetyl coA
(Thiolase)
Acetoacetyl coA
(HMG-coA synthase)
HMG coA
(HMG-coA synthase)
Acetoacetate
Acetone (Acetoacetate decarboxylase) or d-beta-hydroxybutyrate (d-betadehydroxybutyrate dehydrogenase (NADH used))
D Beta hydroxybutyrate as fuel generic
D Beta hydroxybutyrate
(D Beta hydroxybutyrate dehydrogenase (NADH produced)
Acetoacetate
(Beta-ketoacyl-coA transferase)
Acetoacetyl-coA
(Thiolase)
2 acetyl coA
Ketogenesis enzyme order memory
Theo
Took some twins to bed
Ass to ass
Had much gin and
Synthesized
Hot messy gooey liquid == critical!! = only in liver
Hot messy goo is healthy for u = male podcasts = Acetoacetate = Ass to Ass in cars like Andrew Tate
Leads to
Acetoacetate decarboxylase = taking the gas out of wound up assholes
And
D-beta hydroxybutyrate dehydrogenase = dehydrated frat boys
Ketone bodies as fuel memory
D beta frat boy is dehydrated
Acetoacetate = ass to ass believer
Special frat nurse comes in = beta-keto diet = banana Kream diet
= beta keto acyl transferase
Acetoacyl coA = coA added on = banana kream w vitamin A on top
Theo is healed = thiolase = Two thumbs up = 2 acetyl coa
Liver catabolism
Normal diet = amino acids
High blood glucose = glucose
Fasting = fatty acids
Ketone bodies; aas to gluconeogenesis
Why are ketone bodies able to be used as fuel?
Produces atp in other tissues
Can be simplified to acetyl coa = CAC = oxidative phosphorylation
GLUT1
Blood, blood brain barrier, heart
GLUT2
Liver, pancreas, small intestine
GLUT3
Brain, neurons, sperm
GLUT4
Skeletal muscle, adipose tissue, heart
Muscles and fuel
Resting = FFAs
Light workout = blood glucose + FFAs
High activity = glycogen breakdown to lactate + glucose stops being processed (1 glucose molecule processed = 3atp) bc hexokinase not in cytosol when glucose low
**Glycogen to lactate produces atp
Epinephrine is for high activity
What does it generically do
Stimulate release of glucose from liver glycogen
Breakdown of muscle glycogen
Too much lactate = ph down = efficiency of muscles down
==> phosphocreatine for atp
Phosphocreatine enzyme
Phosphocreatine kinase = transfer of Pi group
Ultimate source of ketone bodies
Ketone bodies are produced in liver from acetyl coa
Acetyl coa comes from fatty acids
Which are generated a lot of in liver
But also stored / synthesized in adipose tissue
Ketone bodies are useful because
E source for skeletal/heart muscles and renal cortex
Helps pull out acetyl coa from liver mitochondria even when acetyl coa not being pulled via CAC when glucose levels are down
= cac enables FA oxidation for NADH
HMG-coA synthase location dependence
Liver mitochondrion = ketone body formation
Cytosol = sterol formation
What enzyme key to ketogenesis is only present in liver mitochondrial matrix?
HMG-lyase
= HMG-coA to Acetoacetate
What enzyme does liver not have that makes it unable to process ketone bodies?
Beta-keto-acyl-coA transferase
= Acetoacetate to acetoacetyl coA
Other tissues do not deal with breaking down ketone bodies to get HMG coa
Other tissues: go straight from Acetoacetate to acetoacetyl coA
Liver = acetoacetyl coa to HMG coa
To Acetoacetate
HMG coA structure reminders
6 c
Carboxyl on one end
S coa and c=o other end
Car alcohol +1c co S
Had much gin = special drink = Irish car bomb = car alcohol = 1cup of monoxide = co and some salt/ sulfur
Ch2 c(oh,ch3) ch2 in middle
Had much gin =
cars, alcohol, carssss
When starving
Acetyl coa accumulates
Not being pulled for other types of synthesis
Cac cycle slows down bc intermediates are siphoned off
Ketone body formation helps free coA = fatty acid oxidation can continue = fuels ketone bodies
What is hexokinase iv NOt inhibited by like other hexokinases?
What is it inhibited by?
Glucose 6 phosphate
Liver specific regulator protein = works better when fructose 6 is present = fasting
Glucose Competitively binds to same protein to inhibit its inhibitions
= anchors within nucleus
Where does glycolysis take place in liver cells?
Cytosol
Intestine fuels
Glucose, glutamine, ketones
Microbiome
Lined w bacteria = digestion/ absorption
20-35% of E expenditure
