Glucuneogensis
new production of glucose. makes sugar
Liver glycogen depleted in:
overnight fast
Glucose is the major fuel in
brain
No glycogen stores in the
brain; gets it from bloodstrea.
Uses ketone bodies when
body is starved or uncontrolled diabetes from the breakdown of fat.
Where is the site for gluconeogenesis
Liver; a little in the renal cortex (kidney deals with excess lactate) and intestinal lining
3 carbon precursosrs that are starting point
- Lactate
- Pyruvate
- Glycerol
Where do most gluconeogenesis reaction occur
in the cytoplasm
3 irreversible steps are catalyzed by:
- Hexokinase
- Phosphofructokinase (Rate limiting, commited step)
- Pyruvate kinase (converts PEP to pyruvate and makes ATP)
In gluconeogenesis we need
NADH
Part of converting Pyruvate to PEP occurs in the
mitochondria
Pyruvate or _____usually initate gluconeogenesis
oxaloacetate
Pyruvate usually comes from
skeletal muscle via Cori cycle or nitrogen groups from protein breakdown in skeletal muscle which is sent to liver as alanine
Alanaine and pyruvate are
related; bc they only differ by the carbonyl group
Oxaloacetate comes from
aspartate or TCA cycle; it is an alpha keto acid (amino acid relative, whos sister is aspartate)
What shunts oxaloacetate from TCA cycle
malate shuttle
Glycerol is also a starting point for
gluconeiogenis; it is the backbone for tryglycerides.
No way to build glucose from
acetyl CoA; one exception is glycerol
Kinaseses add
phosphate
Phosphateases remove
phosphate
Glucose 6 phosphatase
removes phosphate grouop from glucose. Bc once its phosphorylated it stays in the cell and we dont want this
Hook on CO2 in one step to make oxalocetate and take it off in next step to make PEP
drive reaction forward. Production of CO2 gas drives reaction forward
Pyruvate carboxylase is found in
mitochondria
CO2 gets attached to pyruvate via
pyruvate carboxylase and goes back into cytoplasm via malate shuttle and is converted from oxaloacetate to PEP
Any time you see additon of CO2 you know it needs which cofactor
biotin
No transporter for
oxaloacetate; you have to convert it to malate via malate shuttle and convert it back to oxoacelatate
Need to take off CO2 and add on phosphate group to make
PEP
Use GTP as a phosphate
donor
PEP synthesis can occur
PEP carboxykinase step
in cytoplasm or mitochondira
Use ATP and ___carrier in the first step of gluconeogenesis
biotin
Use GTP for second step of
gluconeogenesis
Last step of glycolysis and first step of gluconeogenesis are very highly:
regulated.
Biotin attaches
to epsilon amino group of lysine. Makes a flexible structure to move CO2 around the structure
The mitochondria is very :
impermeable; very selective and has a lot of proteins
What are the mitochondrial transporters
- Pyruvate
- PEP
- Malate
Not oxaloacetate!
How are we going to decide whether or not we have to use the mallate shuttle to send oxalocetate out of the cell:
Depends on starting point and whether or not starting point is going to provide us with the NADH we need for gluconeogensis to occur
If starting point is lactate (from muscle glycogen) the first step in the conversion of lactate back to pyruvate once it gets in liver cell provides us:
with NADH that we need to continue with gluconeogenesis; we dont need malate shuttle; we can convert oxaolocaetate to PEP in mitochondria using PEPCK. PEP transporter sends it to cytoplasm to go foward. Didnt have to borrow any reducing power from mitochondria!
If its coming from alanine
protein breakdown
Alanine traseminates to pyruvate. No NADH is produced. Pyruvate goes to mitochondria, converts to oxaloacetate, which converts to malate. Send malate to cytoplasm through malate shuttle and convert it back to oxaloacetate (take off alcohol and make it a keto) using NAD+ and making NADH.
If pyruvate is the main source of carbon:
the malate shuttle is used. By transporting malate to the cytoplasm, reducing power is also moved with it and NADH is produced as malate is converted to oxaloacetate. This NADH is needed for gluconeogenesis to proceed
Malate needs ____to convert malate (from malate shuttle) to oxaloaceate
NAD+
