lecture 9 Flashcards
sources of glucose to support life phases
1-absorptive
2-post absorptive
3-early starvation
4-intermediate
5-prolonged starvation
when is exogenous
absorptive
when is glycogen peaking
post absorptive
when is gluconeogenesis peaking
early to intermediate starvation
gluconeogenesis
is the synthesis precursor of glucose from non-carbohydrate precursors
glucose stores
are depleted during periods of starvation beyond a day
brain relies on glucose
120g/d for energy
glucose must be synthesized
from molecules other than carbs
pyruvate becomes
glucose
2 Pyruvate + 2NADH + 4ATP + 2 GTP + 6 H2O + 2H+
glucose + 2NAD + 4 ADP + 2 GDP + 6Pi
any molecule that can be converted to pyruvate
gluconeogenic
examples of glucogenic molecules
lactate, several amino acids, glycerol
reactions that overcome high negative free energy of irreversible glycolysis reactions
Glucose 6 phosphatase
Fructose 1,6 Bisphosphotase
Phosphoenol pyruvate carboxykinase
pyruvate carboxylase
enzymes in common btw glycolytic and glucogenic pathways
phosphoglucose isomerase
aldolase
trios phosphate isomerase
GAP dehydrogenase
phosphoglycerate mutase
enolase
irreversible glycolytic enzymes
hexokinase
phosphofructokinase
pyruvate kinase
gluconeogenesis enzymes
pyruvate carboxylase
phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase
pyruvate carboxylase
Metabolically irreversible
- Uses biotin as a cofactor
- Allosterically activated by acetyl-CoA
- Anaplerotic for the TCA cycle – replenishes OAA
- Takes place in mitochondria
Phosphoenolpyruvate carboxykinase (PEPCK)
- Synthesis of PEPCK increases in fasting
- Takes place in cytosol
pyruvate is
carboxylated in the mitochondria by pyruvate carboxylase
oxaloacetate
can’t pass out of mitochondria
what happens to OAA instead
it is converted to malate which is then converted to OAA in cytosol
where is oxaloacetate decarboxylated and phosphorylated
in the cytosol by phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase (F1,6BPase)
A metabolically irreversible reaction
F1,6BPase is allosterically inhibited by AMP and fructose 2,6-bisphosphate (F2,6BP)
Glucose 6-phosphatase
Metabolically irreversible hydrolysis reaction
Glucose-6-phosphatase found only in liver and kidney (pancreas and small intestine)
Only those tissues can serve as source of glucose from gluconeogenesis.
Glucose 6-P is a precursor for
glycogen synthesis
glucose synthesis
g6P is the starting spot for
pentose phosphate pathway
glucose 6- phosphotase is present only in
tissues responsible for maintaining blood glucose levels in LIVER AND KIDNEY
in liver
glucose 6-phosphatase is highly regulated
it takes 6 ATP to make glucose
but only 2 are generate in glycolysis
how many more ATP are needed to drive unfavorable gluconeogenesis pathway
4
flux through pathway
is controlled at rate limiting steps
rate determining steps are altered by several mechanisms
- Allosteric control
- Covalent modifications
- Substrate cycles - Futile cycles
- Genetic control - Enzyme concentrations
high amp indicates
that energy charge is low and signals for need ATP
high ATP and citrate
the energy charge is high and intermediates are abundant
why do we care about AMP
prevents both pathways from operating together
refer back to 18 and try to understand it later
carl and gerty cori
Nobel prize in physiology and medicine 1947
cori cycle
interaction of glycolysis and gluconeogenesis
lactate from peripheral tissues
goes to liver and is made into glucose
glucose can go
back to the peripheral tissues
liver
uses lipid for energy
placement of the liver in the circulation
first pass at removing nutrients absorbed from the intestine
liver in circ
can make nutrients available to other major tissues
liver participates in interconversions of all types of metabolic fuels
carbs, amino acids, fatty acids
liver regulates
distribution of fuels and supplies fuel from its own reserves
Pentose Phosphate Pathway
Hexose phosphate Shunt
Production of NADPH
the pyridine nucleotide used for reductive biosynthesis
Fatty acids
Cholesterol
nucleic acids
NADPH also important in
in elimination of oxygen radicals
Formation of ribose 5-phosphate for ribonucleotides
RNA, DNA, certain coenzymes
where in the body is pentose ribose pathway
Not in brain and muscle
Mammary glands, liver, adrenal glands, adipose
enzymes of pentose phosphate pathway are
cytosolic
2 stages of Pentose Phosphate
Pathway:
oxidative and non oxidative
oxidative phase
production of 2 NADPH and ribulose-5-phosphate from glucose-6-phosphate
Pentose Phosphate Pathway: Nonoxidative Phase
Disposes excess pentose phosphates by converting to glycolytic intermediates
Series of C-C bond cleavage and formation reactions
Ribulose 5-P ->Ribose 5-P or Xylulose 5-P
2 Xylulose 5-P + Ribose 5-P ->2 Fructose 6-P + GAP
Transketolase and transaldolase
catalyze the exchange of two- and three-carbon fragments between sugar phosphates
one substrate is an aldose, one substrate is a ketose
NADPH functional roles biosynthetic pathways
FA synthesis (liver, adipose, mammary)
Cholesterol synthesis (liver)
Steroid hormone synthesis (adrenal, ovaries, testes)
NADPH functional roles
Detoxification (Cytochrome P-450 System) – liver
Reduced glutathione as an antioxidant (RBC)
Generation of superoxide radicals (neutrophils): microbicidal activity
regulation
occurs with G6P dehydrogenase
-First step
-Rate limiting
Allosteric Regulation
-Feedback inhibited by NADPH
enzyme induced by insulin
role of NADPH in RBC
Production of superoxide
Hb-Fe2+-O2 -> Hb-Fe3+ + O2-.
Spontaneous rxn, 1% per hour
Both O2-. & H2O2 can produce
produce reactive free radical species, damage cell membranes, and cause hemolysis
