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BI/CH 422/
ANABOLISM OUTLINE:
Overview of Photosynthesis Key experiments: Light causes oxygen, which is from water splitting (Hill) NADPH made (Ochoa) Separate from carbohydrate biosynthesis (Rubin & Kamen) Light Reactions energy in a photon pigments HOW Light absorbing complexes Reaction center Photosystems (PS) PSI – oxygen from water splitting PSII – NADPH Proton Motive Force – ATP Overview of light reactions Carbon Assimilation – Calvin Cycle Stage One – Rubisco Carboxylase Oxygenase Glycolate cycle Stage Two – making sugar Stage Three - remaking Ru 1,5P 2 Overview and regulation Calvin cycle connections to biosyn. C4 versus C3 plants Kornberg cycle - glyoxylate
Carbohydrate Biosynthesis in Animals
precursors Cori cycle
Gluconeogenesis
reversible steps irreversible steps – four energetics 2-steps to PEP mitochondria Pyr carboxylase-biotin PEPCK FBPase G6Pase
Glycogen Synthesis
UDP-Glc Glycogen synthase branching
Pentose-Phosphate Pathway
Regulation of Carbohydrate Metabolism
Anaplerotic reactions
Photosynthesis
Assimilation of CO 2 into
Biomass
cytosol
chloroplast
cytosol
- Plant cells: use 3-C intermediates for further synthesis
- Glyceraldehyde 3-phosphate (G3P) is the most important one.
- made from CO 2 , H 2 O, plus ATP and NADPH from photosynthesis
The C 4 Pathway
C 4 versus C 3 Plants; Benefits of C 4
Plants: Heat and Drought Resistance
- C 4 plants (tropical, hot climates) have an earlier step, in different cells, that isolate Rubisco from the air. - C 4 plants spatially separate CO 2 fixation from rubisco activity, resulting in less reaction of rubisco with oxygen and avoidance of the costly glycolate pathway.
Photosynthesis
- Physical separation of reactions:
- CO 2 is captured into oxaloacetate in mesophyll cells of the leaf.
- Oxaloacetate then passes into bundle-sheath cells where CO 2 is released for Rubisco
- The C 4 pathway has the same energy cost as the glycolate cycle, but also has increased efficiency in heat, which favors the oxidase.
- Another pathway to avoid photorespiration was first discovered in Crassulacae ( C rassulacean A cid M etabolism ( CAM )) in high, dry conditions - Stomata open/close; the CO 2 from C4 fixation is stored as malate in vacuoles.
GlyOXylate Cycle
Photosynthesis
Plants Use Fats and
Proteins for Carbohydrate
Synthesis:
Kornberg Cycle
Recall in
animals:
- Instead of burning isocitrate, it short circuits TCA, taking isocitrate directly to succinate
- The result is the glyoxylate bi-product
- Re-cycle this glyoxylate by making malate from more acetyl CoA in a similar reaction as citrate synthase (^) We’ll come back to this later………….
Gluconeogenesis:
Making “New” Glucose
Gluconeogenesis
Precursors: From what
compounds can glucose be made?
- Animals can produce glucose from sugars or proteins. –sugars: pyruvate, lactate, or oxaloacetate –protein: from amino acids that can be converted to citric acid cycle intermediates (or glucogenic amino acids)
- Animals cannot produce glucose from fatty acids. –product of fatty acid degradation is acetyl- CoA –There is no net conversion of acetyl-CoA to oxaloacetate in Kreb’s Cycle
Plants, yeast, and many bacteria use the Kornberg Cycle to convert acetyl-CoA to oxaloacetate, thus producing glucose from fatty acids.
Gluconeogenesis
The Cori Cycle
made in the liver, although
other organs can reverse
glycolysis, but not deliver
free glucose into the blood
- Synthesis of glucose from
simpler compounds: called
gluconeogenesis
NADH are plentiful
- Other tissues deliver carbon
to liver from “waste”
products.
As you can see the two pathways operate in different tissues, but how is this controlled in a single cell?
Glycolysis versus
Gluconeogenesis
Gluconeogenesis
occurs mainly in
the liver and
Glycolysis occurs kidney cortex.
mainly in the
muscle and brain.
Gluconeogenesis
- Opposing pathways that are both thermodynamically favorable:
- Glycolysis:
- Gluconeogenesis:
- operate in opposite direction
- end product of one is the starting compound of the other
- Seven Reversible reactions are used by both pathways.
- Three ”glycolysis-specific” steps are reversed with Four “gluconeogenesis-specific” steps. - Irreversible reaction of glycolysis must be bypassed in gluconeogenesis. - no ATP generated during gluconeogenesis; instead 6 ATPs and 2 NADH needed per Glc. - Some different enzymes results in the different pathways - differentially regulated to prevent a futile cycle
D G °^ ’^ = –35 kcal/mol D G °^ ’ =–9 kcal/mol
1 Enolase
2 PGM
3 PGK
4 GAPDH
5 TIM
6 Aldolase
7 PGI
Lets look at the energetics of making glucose…..
Gluconeogenesis
3PGA
G3P
P i
Favorable^ P i energetics for Calvin Cycle
Favorable energetics for Gluconeogenesis
Pyruvate
PEP
Changes in Free Energy During
Glycolysis and the Citric Acid
Cycle
There are then 3 points that are novel for gluconeogenesis:
- PyruvateàPEP (complicated)
- Fru 1,6-P 2 à Fru 6-P
- Glc 6-Pà glucose
Gluconeogenesis
Pyruvate Carboxylase
Mechanism
Biotin is a CO 2 Carrier
Gluconeogenesis
Pyruvate Carboxylase
Mechanism
Biotin is a CO 2 Carrier
Gluconeogenesis
Phosphoenolpyruvate Carboxykinase (PEPCK)
Phosphoenolpyruvate to Fru 1,6-P 2
[2Pyr àà2PEP à2 2-PGA à2 3-PGA à2 1,3BPGA à2 GA3P à DHAP à Fru 1,6P 2 ]
Fructose 1,6-bisphosphatase •Fructose 1,6-bisphosphate^ à
fructose 6-phosphate
•Catalyze reverse reaction of
opposing step in glycolysis
- by fructose 1,6-bisphosphatase-
- coordinately/oppositely regulated with PFK
- cleaves phosphate with water
- DOES NOT generate ATP
Oxaloacetate to Phosphoenolpyruvate
G°’ (kcal/m ol)Cum ulative +0.4^ –3.2^ –5.5^ +5.5^ +1.9^ +0.1^ –5.
(in liver) Glucose 6-phosphatase
D G °^ ’^ = –4 –0.4 –3.3 kcal/mol
O O
Fru 1,6-P 2 to Glucose
[Fru 1,6P 2 à Fru6P à Glc6P à Glc]
- Physiologically necessary: Brain, nervous system, and red blood cells generate ATP ONLY from glucose.
- When can’t get it from pyruvate, amino acids are utilized, which allows generation of glucose when glycogen stores are depleted: - during starvation - during vigorous exercise - can generate glucose from amino acids, but not fatty acids
- Costs 4 ATP, 2 GTP, and 2 NADH. Net reaction:
2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H +^ + 4 H 2 O à
Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+
Gluconeogenesis
D G ° ’^ = –9 kcal/mol
Why do we need glucose?
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