Blood glucose concentration is about ___ millimolar (about ____ milligrams per deciliter)
5
90
given that the blood glucose concentration is 5 mM how many grams of glucose are in the blood?
6
what are the three major sources for blood glucose?
alimentary glucose (food glucose)
glucose released from storage (glycogen)
glucose made from proteins (food but not directly
what is the glucose oxidation equation
Glucose + 6O2 --> 6CO2 + 6H2O + energy
glycolysis occurs in the cytosol and the products of the two pathways in glycolysis are
anaerobic: lactate, 2 ATP, water
aerobic pyruvate, 2 ATP, NADH + H+ and water
where does the TCA cycle occur
in the mitochondrial matrix
where does the ETC occur
inner mitochondrial membrane
T/F: the presence of pyruvate at the end of glycolysis makes it anaerobic
FALSE
the presence of lactate---pyruvate is aerobic and anaerobic (right before the conversion to lactate happens)
how does glucose get into the cells before glycolysis can occur?
GLUTs and SGLT
where does the lactate go after anaerobic glycolysis
it stays in the cytosol
Why do we have an inefficient process (less ATP) such as anaerobic? (2)
Easier and less complicated
Gives us ATP when we don’t have the resources to do the aerobic route
tissues that use anaerobic glycolysis
tissues with few or no mito
RBC
leukocytes
lens
cornea
medulla of the kidney
testes
ischemic tissues (tissues which cannot utilize the blood supplies
what type of fibers are in skeletal muscles in humans?
type 1 and type 2
aerobic muscle fibers that are rich in mitochondria and myoglobin
dominant in muscles associated with endurance (legs, back)
Relatively resistant to fatigue
slow twitch
Type 1
Type 1 fibers are ___ twitch
slow
more anaerobic muscle fibers with fewer mito and myoglobin
dominant in muscle associated with rapid movement, easily fatigued
fast twitch
Type 2
Type 2 fibers are ____ twitch
fast
5 initial steps of glycolysis who's net effect is ____
they convert glucose (6 C) to ____ (3 C)
endergonic
triose phosphates
after the 5 initial steps, the 5 additional steps who's net effect is such that they are ____
exergonic
what are the three irreversible glycolytic enzymes which are regulatory
hexokinase
phosphofructokinase
pyruvate kinase
the three irreversible glycolytic enzymes are all characterized as being highly
exergonic
hexokinase and glucokinase are _____ of each other
isozymes
not an allele
glucose is converted to G6P by which enzyme?
does this step use or produce ATP?
hexokinase
use ATP
G6P is converted to fructose 6 phosphate (ketose) by which enzyme?
phosphoglucose isomerase
____ is easily saturated as product inhibition keeps the activity below Vmax
hexokinase
enzyme that functions to removed glucose from the blood
Glucokinase
_____ has a high capacity, but a might lower affinity (higher Km)
glucokinase
_____ has a much lower capacity, but a much higher affinity (lower Km)
hexokinase
How do the liver and pancreas respond to glucose being removed from the blood by glucokinase?
The liver will respond by channeling glucose into storage pathways, while the beta cells of the pancreas will respond by secreting insulin.
When post-prandial (after a meal) levels of glucose are ____, liver _____- allows the liver to take up circulating glucose and store it as ____.
high
glucokinase
glycogen
The absence of product inhibition of ____ serves to ensure that _____ uptake and storage of blood glucose (glycogen) can continue.
glucokinase
liver
the low km of hexokinase allows tissues
to efficiently phosphorylate glucose when glucose is in low supply
because G6P will stay within the cell and won't diffuse out via GLUTs (GLUTs don't recognize g6p)
Mice deficient in glucokinase regulatory protein do not respond rapidly to injected glucose. This metabolic impairment is thought to be due to the absence of a ____ ____ _ _______.
nuclear reserve of glucokinase
If you don’t have the GKRP the GK wont be in a storage place in the nucleus (they will be floating all over the place)—cant easily take it and put it back freely in glycolysis
in the presence of ____ glucokinase will be removed from its inactive form in storage and will be available to use
glucose
in the presence of ____ glucokinase will go back into storage (inactive form) and will be unavailable
F6P
where are glucokinase and glucokinase regulatory protein located?
in the nucleus
ATP and citrate turn off the conversion of F6P to F16BP via phosphofructokinase 1
why?
ATP—you clearly have enough of ATP so the cycle that makes ATP stops
Citrate is a signal that you have enough energy so it turns off the enzyme
AMP and fructose 2,6 BP turn on the conversion between F6P to F16BP via phosphofructokinase 1
why?
AMP turns on the enzyme because if you have a lot of AMP you don’t have a lot of ATP and you need to continue the pathway to get it
PFK-1 can be regulated allosterically by elevated levels of the following energy-associated signals:
activated:
inactivated:
activated: AMP
inactivated: ATP, citrate
inhibition of PFK-1 leads to the accumulation of G6P which can be routed towards (3)
gluconeogenesis
glycogenesis (glycogen synthesis) in musce or liver
hexose monophosphate shunt (PPP)
regulatory enzymes of glycolysis in general can be activated by (3)
Insulin
AMP
Substrate
Regulatory enzymes of glycolysis, in general, can be inhibited by (7)
glucagon (made in alpha cells)
ATP
NADH--you have enough of these, don't need more
cyclpe AMP
Acetyl CoA
Citrate
Product inhibition
elevated insulin/glucagon ratio promotes ______
glycolysis
elevated glucagon/insulin promotes ______
gluconeogenesis
True/False: ingestion on a regular basis of CHO or administration of insulin can elevate the levels of these glycolytic enzyme transcripts
____ is made as a side product in anaerobic glycolysis
able to be used in RBC when there are low oxygen levels
2,3 BPG
nAbout 15-25% of glucose converted to lactate in erythocytes is shuttled through BPG shunt, while very minute amounts are shuttled through BPG shunt in other cell types
hypoxia induces synthesis of _____
2,3 BPG
T/F: pyruvate kinase adds a P to the substrate
FALSE
it removed a P from phosphoenolpyruvate to pyruvate
T/F: pyruvate Can have abnormal Km or Vmax, can show an abnormal response to F16BP
true
glucagon indirectly (via a second messenger system) phosphorylates ____ ____ thusly inactivating it
pyruvate kinase
inhibiting pyruvate kinase inhibits ___ and promotes ____ in the liver and kidney
glycolysis
gluconeogenesis
heredity deficiency of ____ (insulin independent transporter) can lead to seizures in infancy and delayed development
GLUT-1
deficiency of a specific isoform aldolase can lead to _____ ____
hemolytic anemia
deficiency of ___ ___ ____ can lead to hemolytic anemia and neurological symptoms
triose phosphate isomerase
pyruvate kinase deficiency affects about ___ per ____ individuals and this is considered relatively ____ for a genetic diseases
1 per 10,000
Phosphofructokinase deficiency is a ___ ____ disease
glycogen storage
Will have a problem with glucose-6-phosphate accumulate and therefore you will have problems with glycogen storage
The severity of the disease is a function of both ______ activity and activation of _____ mechanisms
enzymatic
compensatory
What is the reason that some RBCs are so affected with pyruvate kinase deficiency?
No redundancy—RBC have no alternative pathways to get from point A to point B—no organelles, etc
_____ deficiency in mince appears to be protective against malaria
pyruvate
why is sodium fluoride generally added to blood samples prior to reading blood glucose levels
As cells are taking up glucose they are also breaking it down (going through glycolysis) and to stop that process they add fluoride to inhabit enolase (which is an enzyme of glycolysis)
what are the two mechanisms of arsenic toxicity
Disruption of sulfhydryl-containing enzymes
Substitution of phosphorus anion in phosphate, preventing net ATP and NADH synthesis while allowing glycolysis to proceedGlycolysis will continue, aren't totally killing it but
pyruvate is reduced to lactate by which enzyme?
lactate dehydrogenase
Structure of pyruvate
(3 carbons--two are present from the splitting of a 6 C glucose molecule)
structure of lactate
2 Hs are added from pyruvate --to the O and to the previously carbonyl C
the conversion from pyruvate to lactate serves to
oxidize NADH to NAD+, prodiving more NAD+ for continuing glycolysis
The reaction of pyruvate to lactate is reversible or irreversible?
reversible
Why is the production of lactate in anaerobic glycolysis so important
NADH in anaerobic glycolysis wont be taken to the mitochondria to be oxidized to NAD+ and therefore it could build up and if there is no more NAD+ glycolysis can stop all together
NADH is oxidized to NAD+ in the _____
mitochondria
In the absence of oxygen, the NAD+ is regenerated by the formation of _____
lactate
the following tissues derive their energy from anaerobic glycolysis (6)
erythrocytes
skeletal muscle in a state of great exertion
lens and cornea of the eye
testes
leukocytes
kidney medulla
After lactate is formed it diffuses for the tissue into the blood and there can be used by the liver for _______
gluconeogenesis
lactate cane be use by the heart or kidney to regenerate ____ which is further oxidize aerobically in the mitochondria
pyruvate
Is lactate responsible for most of the muscle soreness felt on days following physical exertion?
no
they used to think that it was the build up of lactate causing this but now people say it due to the tears in muscle
glucose oxidation consists of 3 processes
Glycolysis
TCA cycle (occurs in mito matrix)
Electron transport chain (occurs in inner mitochondrial matrix)
the ETC is involved with (2)
electron transport
oxidative phosphorylation
glycolysis generates __(1)___ from ___(2)__
(1) is oxidized to 2 in the mitochondria
NADH
NAD+
the regeneration of NAD+ by the formation of lactate is catalyzed by
lactate dehydrogenase
Conditions that raise the NADH/NAD+ promote the formation of lactate (7)
CO poisoning
sickling crisis
ischemic tissue
myocardial infarction
mitochondrial disease
warburg effect
alcohol intoxication
how does CO poisoning promote lactate formation?
it causes Hb to hold onto O2 better and it won't release the O2 to the tissues and so your mito won't be working well and the NADH will not be metabolized but he mito and ti will build up and raise the NADH level
how does a sickling crisis promote lactate formation
sickle cell patents only have this (anemia and crisis) and it is associated with O2 problems in mitochondria won't be working well and you won't be able to metabolize the NADH and it will build up
how does ischemic tissue promote lactate formation
tissue doesn't have enough oxygen due to cardiovascular issues
how does mitochondrial disease promote lactate formation
generic disease, and so chronic inability to metabolize NADH bc mito isn't working well
how does Warburg effect disease promote lactate formation
cancer cells are anaerobic (don’t have to be but they are—so not really explained), thought to be a result of mutation and once it becomes cancerous it starts the warburg effect
If you have more NAD+ you promote the formation of _____
if you have more NADH you promote the formation of_____
pyruvate
lactate
Cancer cells are thought to be due to mutations in the two genes
Oncogenes—go into over drive and more are made and they make cancer
Tumor suppressor genes—the defense against cancer crumbles and you cannot fight against the cancer
True/False: the mitochondria is involved in apoptosis of cancer cells
TRUE
how does alcohol intoxication promote lactate formation
The oxidation of alcohol results in significant amounts of NADH in the liver which raises the ratio of NADH and NAD+
why is NADH produced during alcohol oxidation?
the dehydrogenases involved in alcohol metabolism take Hs away and add them to NAD+ forming NADH
How is ethanol metabolism related to NADPH
Alcohol is a xenobiotic and therefore the liver’s cyp system metabolizes it using NADPH
^the cyp system being used is very important because alcohol can be very harmful to us
what is MEOS
microsomal (the smooth ER) ethanol oxidizing system
Lactic acidosis results from the overproduction (or underutilization) of _____ ____
lactic acid
nemonic device for the steps of the TCA cycle
CItric Acid Is Krebs’ Starting Substrate For Mitochondrial Oxidation
C—Citrate (citric acid)
I—isocitrate
A—alpha ketoglutarate
S—succinyl Co-A
S—succinate
F—furmate
M—malate
O--oxaloacetate
Acetyl CoA (acetyl part) has ___ carbons, oxaloacetate has ____ carbons and they combine to form citrate which has ___ carbons
TWO
FOUR
SIX
The TCA cycle represents the metabolic destination for the oxidation of ____, ___ and ____
CHO
proteins
lipids
The ____ ____ participates in processes such as transamination, deamination, lipogenesis, and gluconeogenesis.
TCA cycle
The TCA cycle produces the reduced co-enzymes ___ and ____ that provide substrates for the ETC, which subsequently oxidizes these substrates
NADH
FADH2
True/False: Few (very little) genetic defects associated with TCA cycle have been identified in humans, as there are none at the present time
FALSE
there are none as the severity of these defects might present an overwhelming metabolic challenge--Make a slight change the human cannot survive because these enzymes are so essential so they cannot be tested
is the TCA cycle is anabolic or catabolic?
BOTH
it is amphibolic
Almost all of the TCA enzymes are located in the
mitochondrial matrix
Acetyl CoA can be formed from ___ and ____
fatty acids
amino acids
what is the precursor molecule for the synthesis or ketone bodies, fatty acids and cholesterol
Acetyl CoA
what is the enzyme that forms acetyl CoA from pyruvate
NADH--this is one of the products of the TCA cycle so don't need more (negative feedback/product) inhibition
Where does the CO2 come from in the production of Acetyl CoA?
it is from the pyruvate (leaves from the molecule)
activity of pyruvate dehydrogenase complex requires specific nutrients (5)
thiamine
panthothenic acid
niacin
riboflavin
lipoic acid
**all B vitamins
how can alcohol affect the activity of pyruvate dehydrogenase complex?
alcohol depletes the body of certain B vitamins and since the PDH complex requires B vitamins for function it an inhibit the activity
PDC is allseoterically inhibited by elevated levels of ___ ____ and ____
NADH
ATP
Acetyl CoA
ATP, acetyl CoA, NADH will activate the ____ to inactivate PDH complex
kinase
T/F: the phosphorylated PDC is inactive
true
why do ATP, NADH and Acetyl CoA inactivate PDC by activated protein kinase?
because these are products and we have enough so it inhibits the going forward of the reaction
PDC is activated by what?
calcium
calcium activates phosphoproteinkinase which cleaves the P from PDC and activates it
pyruvate ____ the inactivation of PDC
inhibits
why does pyruvate inhibit the inactivation of PDC
Pyruvate inhibits the inactivation of pyruvate dehydrogenase because if there is a lot of it present the reaction will want to go forward and if it is inhibiting the inactivation of it, it will make it go forward
How many ATP are produced for every NADH molecule
~3
How many ATP are produced for every FADH2 molecule
2 Hs are added from pyruvate --to the O and to the previously carbonyl C
