glycolysis n krebs Flashcards
why do we need glycerol 3 phosphate shuttle?
ETC is located in the inner membrane of mitochondria which is impermeable to the NADH that has been produced OUTSIDE the mitochondria (like in glycolysis) Howver the NADH produced in the mitochondria is fine because its already there
- NADH is used to reuced DHAP giving us glycerol 3 p. by the enzyme glycerol 3 p DH 1
- A similar enzyme is located in the outer mitchondrial membrane which glycerol 3 phosphate 2 uses FAD to take the H from glycerol 3 phosphate, reforming DHAP
- FADH2 gives the H to co enzyme q
how many NADH produced by glycolysis
2
substrate level phosphorylation
in glycolysis when we form ATP when 1,3 biphosphoglycerate gives a phosphate to ADP we form overall 2 atps and also the last step with pyruvate kinase
how does glucose enter the cell
through NA glucose transporter, examples of secondary active transport because the na gradient was created by a pump
GLUT 1 GLUT 2 3 4 5
- all cells but especially brain and RBC
- liver,SI,kidney (hyper) low affinity high KM
3.Brain neurons (hypo) high affinity but low Km
adipose tissue and muscle
5 enterocytes
what is the fate of glucose in liver
enzyme glucokinase makes glucose 6 phospate and then proceeds to make glycogen
glucose and pancrease
glucose enters glycolysis, atp produced increases ca2+ levels and then triggers insulin release by exocytosis
regulatory enzymes of glycolysis
ALL OF THE KINASES
1. hexokinase- inhibited by its products
2. phosphofructokinase
- :( ATP
:( reducing equivalents
:( citrate
:) activated by fructose 2,6 bisphosphate
3. PK
AAAF
:( alanine, acetyl coa , atp, fatty acids
:) fructose 1,6 biphosphate
comparison of hexokinase and glucokinase
H
- found in all cells
- not specific to just glucose
- inhibited by product glucose 6 p
- high affinity for glucose
- has 4 isoforms
- not activated by insulin
G
- found only in liver
- low affinity for glucose
- not inhibited by its product
- is most effective when the level of glucose is high in the blood so after a meal which means its activated insulin
committed step in glycolysis
phosphofructokinase
- highly regulated
- highly exergonic reaction
fate of pyruvate
depends on whether its anaerobic or aerobic
anaerobic- produce lactic acid (RBC, muscles) LDH
aerobic_ oxidative decarboxylation of pyruvate to acetyl co- A
what is an additional function of pyruvate
serves as a fuel source for cardiac muscle and brain nerurons
phosphofructokinase
major regulatory enzyme
- :( citrate (makes sense because its a catabolic process)
:) fructose 2,6 bisphosphate (is an indicator of high glucose level)
:( ATP + reducing equivalents
fructose 1,6 bisphosphate and fructose 2,6 biphosphate
1,6 - :) PK
2,6 :) phosphofrcutokinase
regulation of pyruvate kinase
AAAF- atp,alanine,acetyl coa , fatty acids
:) fructose 1,6 bisphosphate
similar to glycogen synthase is active in its OH form
insulin - activate
glucagon-inactivate
when do you mention the glycerol 3 phosphate
glycolysis
fatty acid synthesis
what is the point of citrate shuttle and explain it (draw)
need to get the acetyl coa from mitochondria to cytoplasm for e.g fatty acid synthesis
in mitochondria acetyl coa+ oxaloacetate to make citrate
citrate leave mitochondria to go cytoplasm where its cleaved back to products (citrate lyase)
the oxaloacetate, its goal is to be converted back to pyruvate.
- reverse of krebs———malate (malate DH)
- Malic enzyme - produces Nadph gives pyruvate
malate+NADP—–pyruvate co2 + NADPH - pyruvate translocase transports to mitochondria
anoplerotic reaction
pyruvate carboxylase forms oxaloacetate
how do we reverse glycolysis
7 of the enzymes are the same apart from 3. 2/3 use simple hydrolysis reactions and the other one is split into 2 enzymes
- glucokinase
glucose 6 phosphatase - phosphofructokinase
fructose 1, 6 biphosphatase - PK
pyruvate to oxaloacetate =pyruvate carboxylase
oxaloacetate —– phosphoenolpyruvate (phosphoenolpyruvate carboxykinase)
when do you mention the malate shuttle
glycolysis
gluconeogeneisis
fructose 1, 6 bisphosphatase
one of the bypass enzymes involved for gluconeogenesis
it breaks down fructose 1, 6 phosphate into fructose 6 phosphate
:) citrate
:(frucots 2, 6 bisphosphate because that is AN IDICATOR OF HIGH GLUCOSE AVAILABILITY
what is the role of fructose 2,6 biphosphate
is an indicator of high glucose ability
pyruvate carboxylase
a mitochondrial enzyme
b7
atp
needs acetyl coa (because theres no point of making oxaloacetate if there is no acetyl co a to facilitate krebs
where does gluconeogenesis occur
cytoplasm!
malate aspartate shuttle
In order for gluconeogenesis to occur need oxaloacetate which is produced in the mitochondria but gluconeogenesis happens in the cytosol. but oxaloacetate cannot leave through the inner mitochondrial membrane.
route 1- converted to malate
route 2 _ aspartate
when do you mention the malate shuttle
gluconeogenesis
deficiencies regarding gluconeogenesis
- fructose 1,6 biphosphatase
blocking of gluconeogenesis leading to hypoglycemia and LACTIC ACIDOSIS
between meals the blood glucose is maintained only by glycogenolysis
Hypoglycemia of the neonate
-brain consumes a lot of glucose
-they have small amount of adipose tissue for an alternative fuel source
the enzymes of gluconeogenesis may not be completely functional at this time
-smaller glucose stores
PFK1 isoforms
muscle
constitutive
high glycolysis during exercise .
liver
- inducible
- by insulin
specially activated by fructose 2, 6 biphosphaste
name the products of krebs
citrate
cis aconitate
isocitrate
a ketoglutarat
how many atps directly from krebs
1
how many indirect atps
11
cos 3 Nads
1 fad
which enzyme uses fad as a cofactor for krebs
succinate dh
where do we generate the direct atp from
from the cleavage of succinyl coa````````````
substrates and products of krebs
substrates (basically first step)
1. OAA
ACETYL COA
WATER
products
- nadh
- fadh2
- co2
- atp
regulation of krebs
3 irreversible reactions
- citrate synthase
- isocitrate DH
- alpha k glutarate DH
PDH regualtion
OH IM PYRUVATE AND IM ACTIVE:)
:(atp + reducing equivalents and acetyl coa
:) promoted by any sudden demand upon the cell signalled by calcium
anoplerotic reaction
chemical reactions that form intermediates of a metabolic pathway like krebs. Because the intermediates don’t just have the sole purpose of making atp but other things to
what other roles does oxaloacetate have
- glucose
- aa (aspartate)
functions of krebs
- ATP
2. Building blocks for other things
what do the intermediates form in krebs
citrate- fats a k glutatarate- aa glutamine and glutamate and GABA succinyl- heme+porphyrin oxaloacetate- aa aspartate + glucose malate-glucose
oxidative phosphorylation
process in which ATP is formed as a result of the transfer of electrons from NADH or FADH 2 to O 2 by a series of electron carriers. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms
