week 7 Flashcards
metabolically irreversible and regulated steps in glycolysis
#1 (hexokinase) #3 (phosphofructokinase) #10 (pyruvate kinase)
Gluconeogenesis irreversible step enzymes
Phosphatase enzymes
Pyruvate kinase-Pyruvate carboxylase /
PEP carboxykinase
Phosphofructokinase - Fructose-1,6-Bisphosphatase
Hexokinase - Glucose-6-Phosphatase
location of gluconeogenesis
cytoplasm of liver and kidney cells
why is CO2 used in the first step of gluconeogenesis
to increase the entropy of the reaction and drive it forward
Pi
inorganic phosphate
pyruvate carboxylase
converts pyruvate to oxaloacetate. phosphorylates CO2 and adds it to pyruvate
PEP Carboxykinase
Conversion of oxaloacetate to PEP
GTP is hydrolyzed to provide energy and donates a phosphoryl group
Fructose-1,6-bisphosphatase
Hydrolysis of F-1,6-BP to F-6-P
Fructose-1,6-bisphosphatase regulation
Allosteric regulation:
citrate stimulates (**Why this?!)
fructose-2,6-bisphosphate inhibits
AMP inhibits (doesnt have enough energy to make glucose for the body)
Glucose-6-Phosphatase
Conversion of Glucose-6-P to Glucose
occurs in the ER of liver cells
Why does glucose conversion occur in the ER
ER vesicles filled with glucose diffuse to the plasma membrane, fuse with it and open, releasing glucose into the bloodstream.
Lactate Recycling
cori cycle
pyruvate is reduced to lactate. Lactate is then returned to the liver, where it can be reoxidized to pyruvate by liver LDH. Liver provides glucose to muscle for exercise and then reprocesses lactate into new glucose
Regulation of Gluconeogenesis
Inhibited by glycolysis
Important steps are regulated
Undernourished person consuming alcohol leads to…
hypoglycemia
How can alcohol cause hypoglycemia
Ethanol inhibits liver gluconeogenesis since the liver cannot metabolize the excess reducing equivalents (NADH) made by oxidizing ethanol. This blocks conversion of lactate to glucose, promotes conversion of alanine to lactate, can even create mild lactic acidosis
Glycogen
animal storage of glucose) is a long polymer of glucose – long chains connected by a-(1–>4) bonds, and branches connected by a-(1–>6) bonds
Starch
is the plant form of glucose storage
How is glycogen and starch catabolized?
Amylase is an endoglycosidase. It cleaves dietary amylopectin or glycogen to maltose, maltotriose and other small oligosaccharides. It is active on either side of a branch point, but activity is reduced near the branch points
Is tissue glycogen different from dietary glycogen?
Yes. Tissue glycogen’s breakdown is carefully controlled.
Metabolism of tissue glycogen
Glycogen phosphorylase cleaves glucose from the nonreducing ends of glycogen molecules
This is a phosphorolysis
How Is Glycogen Synthesized?
Glucose units are activated for transfer by formation of sugar nucleotides
UDP-glucose pyrophosphorylase
driven by pyrophosphate hydrolysis.
The reaction is a phosphoanhydride exchange, with a phosphoryl oxygen of glucose-1-P attacking the a-phosphorus of UTP to form UDP-glucose and pyrophosphate.
Glycogenin
a protein that forms the core of a glycogen particle
Glycogen synthase
transfers glucosyl units from UDP-glucose to C-4 hydroxyl at a nonreducing end of a glycogen strand
How Is Glycogen Metabolism Controlled
A highly regulated process, involving reciprocal control of glycogen phosphorylase and glycogen synthase.Both enzymes are regulated by covalent modification - phosphorylation
Glycogen phosphorylase regulation
allosterically activated by AMP and inhibited by ATP, glucose-6-P and caffeine
glycogen synthase regulation
is stimulated by glucose-6-P
Glucagon and epinephrine (hormone regulation)
stimulate glycogen breakdown - opposite effect of insulin
insulin (hormone regulation)
stimulates glycogen synthesis and inhibits glycogen breakdown
Pentose Phosphate Pathway (PPP)
Provides NADPH for biosynthesis
Produces Ribose-5-P
Two oxidative processes followed by five non-oxidative steps
PPP location
Operates mostly in cytoplasm of liver and adipose cells
NADPH is used in cytosol for fatty acid synthesis
Oxidative steps of PPP
- Glucose-6-P Dehydrogenase (G6PD)*
Irreversible 1st step - highly regulated! - Gluconolactonase
Uncatalyzed reaction happens too - 6-Phosphogluconate Dehydrogenase
An oxidative decarboxylation (in that order!)
Non-oxidative steps
Makes a bunch of different types of sugars through 4 types of reactions
Variation on the PPP depends on..
what product is needed at the moment. Such as ribose-5-P, NADPH, or ATP
Central metabolism
glycolysis and TCA cycle
reciprocal regulation of metabolic pathway enzymes
Allosteric regulation of enzymes (modulated) Covalent modification (de)phosphorylation
metabolic processes in the cytoplasms
fatty acid synthesis, glycolysis, most gluconeogenesis rxns, pentose phosphate pathway
metabolic processes in the mitochondria
TCA cycle, oxidative phosphorylation, fatty acid breakdown
during glycolysis, 1 glucose gets converted into…
2 pyruvate molecules
Pyruvate can be further metabolized to
Lactate or ethanol (anaerobic) Acetyl CoA (aerobic)
Net ATP of glycolysis
2 ATP.
2 ATPs used, 4 ATPs made
2 stages of glycolysis
hexose and triode stage
3 metabolically irreversible steps of glycolysis
- Hexokinase
- Phosphofructokinase
- Pyruvate Kinase
Hexokinase
phosphorylates glucose to generate glucose-6-phosphate (G6P)
Isozyme
multiple forms of an enzyme
Phosphofructokinase-1 (PFK-1)
Catalyzes transfer of a phosphoryl group from ATP to F6P to form fructose 1,6-bisphosphate (F1,6BP)
phosphofructokinase-2 (PFK-2)
synthesizes fructose 2,6-bisphosphate (F2,6BP)
Regulation of Phosphofructokinase-1
inhibited by high levels of citrate, ATP, and F2,6BP
activated by AMP
Pyruvate Kinase (PK)
converts phosphoenolpyruvate (PEP) into pyruvate
Metabolism of Pyruvate to Ethanol (yeast - anaerobic)
Two reactions required:
(1) Pyruvate decarboxylase
(2) Alcohol dehydrogenase
The Pasteur Effect
the slowing of glycolysis in the presence of oxygen
(This is due to the fact that more ATP is produced under aerobic conditions than under anaerobic conditions, therefore less glucose is consumed aerobically )
Reduction of Pyruvate to Lactate (muscles - anaerobic)
Muscle lactate dehydrogenase converts pyruvate to lactate
This reaction regenerates NAD+ for use by GAPDH in glycolysis