16. fermentation and gluconeogenesis Flashcards
what happens to pyruvate under aerobic conditions
it’s oxidized to Acetyl-CoA, centers the CAC, and is oxidized to CO2 and H2O
what happens to pyruvate under anaerobic conditions
pyruvate undergoes fermentation to either lactate or ethanol
what can pyruvate ferment into
lactate or ethanol
where would pyruvate ferment into lactate
in animal tissues
where would pyruvate ferment into ethanol
in yeast
what else is produced in pyruvate fermentation
NAD+
why is NAD+ produced in pyruvate fermentation
it is regenerated to continue being used in glycolysis as a co-substrate
what enzyme reduces pyruvate into lactate
lactate dehydrogenase
lactate is the ionized form of ___
lactic acid
describe the G’o value for pyruvate fermentation into lactate
it has a large negative G’o
describe why there is no net accumulation of NAD+ as it’s produced by fermentation
glycolysis uses NAD+ to make NADH while fermentation replenishes NAD+. So long as both are occurring, there is no net change in the NAD+ and NADH pools
where does fermentation to lactate occur in humans
active skeletal muscles, red blood cells, and a few other cell types (ie sperm, retinal, brain, and kidney cells)
describe fermentation in active skeletal muscles
O2 (temporarily) cannot be bright in from the lungs fast enough. Muscle glycogen stores provide extra glucose for lots of glycolysis
describe fermentation in red blood cells
RBCs lack mitochondria when mature, so they cannot complete aerobic respiration
describe fermentation in the other human cell types (sperm, retinal, brain, kidney)
glycolysis in these cell types is the only method of producing ATP even in aerobic conditions
T or F: lactate can be recycled
true
where can lactate be recycled
in the liver
describe how lactate is recycled in the liver
lactate is brought to the liver via blood and is slowly reconverted to pyruvate by lactate dehydrogenase working in reverse, and then to glucose by gluconeogenesis
how are glycogen stores refilled
heavy breathing after exertion repays O2 debt and allows reformation of depleted glycogen stores
T or F: some bacteria can undergo lactic acid fermentation
true
describe lactic acid fermentation in bacteria
one such bacteria ferments the lactose in milk. The resulting pH drop precipitates milk proteins = yogurt
describe the first step of ethanol fermentation (what is produced + enzyme used)
pyruvate is converted to acetaldehyde via pyruvate decarboxylase. CO2 is also produced
is the first step of pyruvate fermentation in yeast reversible
no
in the first step of pyruvate fermentation in yeast, what does the enzyme require
Mg2+ and a coenzyme called TPP
what is TPP
- derived from vitamin B1
- we need it for synthesis of Acetyl-CoA and in the Pentose Phosphate Pathway
describe the second step of ethanol fermentation
acetaldehyde is converted to ethanol via alcohol dehydrogenase. NAD+ is also produced
describe what cool stuff pyruvate decarboxylase is responsible for
carbonation in champagne, beer, rising dough
describe the function of alcohol dehydrogenase in HUMANS
it allows us to oxidize ingested ethanol in our liver to acetaldehyde and then to acetate and water (reverse reaction of fermentation). NAD+ is reduced to NADH
what are the other two fates of pyruvate
it can be carboxylated to oxaloacetate for the CAC, or it can have an amine group added to form alanine
explain why tumors are initially growing under hypoxic conditions
in the early stages, there aren’t a lot of blood vessels around it = not a lot of oxygen = anaerobic conditions
describe the rate of glycolysis in a growing tumor cell
the rate is about 10 times as fast in a growing tumor cell since the yield of glycolysis is so low
describe the cellular changes that occur in a tumor cell (bad for us, good for the tumor)
- disrupted mitochondrial electron transport
- upregulation of glycolysis enzymes
- upregulation of glucose transporters on the PM
- upregulated lactate dehydrogenase
how do chemotherapeutic agents disrupt glycolysis
by inhibiting hexokinase
describe the other benefit of preventing G6P formation by inhibiting hexokinase
G6P is used in the pentose phosphate pathway which is used to synthesize nucleotides. No G6P=not enough nucleotides to supply constant cell division and DNA doubling. Tumor growth slows
describe what a PET scan does/what it’s used for
the patient is injected with a labeled glucose analog that fluoresces which is taken up by tissues but cannot be metabolized. Accumulation of the analog allows us to view/detect nascent tumors
what is gluconeogenesis
synthesis of glucose from non-carbohydrate precursors
how many carbons is the starting material of gluconeogenesis
can be 2C or 3C
what is the starting material of GNG in mammals
lactate, pyruvate, glycerol, and some gluconeogenic amino aicds
where does GNG occur in mammals
the cytosol of the liver
which part of the GNG pathway is consistent in both plants and animals
PEP to G6P
how many steps do GNG and glycolysis share
7 of 10
which steps of glycolysis are not shared with GNG
glucose to G6P (1)
F6P to F1,6P (3)
PEP to pyruvate (10)
which steps of GNG are irreversible: the 7 shared or the 3 unshared with glycolysis (+why)
the 3 unshared steps are irreversible because GNG needs three different enzymes to bypass the steps
what are the two possible pathways to produce PEP from pyruvate
- one when pyruvate is predominant
- one when lactate is predominant
which amino acid is prevalent in skeletal muscle as it’s degrading proteins for fuel
alanine
how is alanine made
pyruvate + amino group =alanine
what is transamination
the joining of an amino group to pyruvate to make alanine (aka swapping an amine group from one molecule to another)
what enzyme completes transamination
aminotransferases
an amino group lacking its amine group is called ___
an a-keto acid
what is the a-keto acid of alanine
pyruvate
what do aminotransferases require
PLP (a vitamin B6 derivative)
where is alanine prevalent
skeletal muscle
where does alanine travel to
the liver
what happens to alanine in the liver
it loses the amine group and becomes pyruvate
GNG step 1, pyruvate predominant: where is pyruvate moved to from the cytosol
the mitochondria
GNG step 1, pyruvate predominant: what happens to pyruvate in the mitochondria
it’s carboxylated to form oxaloacetate
GNG step 1, pyruvate predominant: what enzyme converts pyruvate to oxaloacetate
pyruvate carboxylase
GNG step 1, pyruvate predominant: what does pyruvate carboxylase require
biotin and ATP
GNG step 1, pyruvate predominant: what is the role of bicarbonate
it provides the extra CO2 group in oxaloacetate formation
GNG step 1, pyruvate predominant: what is the role of biotin
it serves as a long arm that swings the carboxyl group between the two enzyme sites
GNG step 1, pyruvate predominant: what is the role of the extra carboxyl group
it serves to prime pyruvate
GNG step 1, pyruvate predominant: now that we have oxaloacetate, what is the next step
it needs to be converted to PEP
GNG step 1, pyruvate predominant: can oxaloacetate directly be converted to PEP
no
GNG step 1, pyruvate predominant: how do we convert oxaloacetate to PEP
it’s reduced to malate by malate dehydrogenase in the matrix. Malate can then leave the mitochondria, enter the cytosol and be reconverted to oxaloacetate
GNG step 1, pyruvate predominant: describe [NADH] in the cytosol and the matrix
NADH in the matrix is converted to NAD+, so that molecule of NAD+ is used in the cytosol to make NADH, so this process increases cytosolic NADH levels
GNG step 1, pyruvate predominant: what happens once oxaloacetate is in the cytosol
it is decarboxylated and phosphorylated to from PEP
GNG step 1, pyruvate predominant: what molecule phosphorylated OAA to become PEP
GTP
GNG step 1, lactate predominant: we have lactate produced in the muscle. What happens to it
the Cori Cycle shuttles it to the liver
GNG step 1, lactate predominant: once lactate is in the liver, what happens
it will be reconverted to pyruvate and reproduce NADH
GNG step 1, lactate predominant: do we need the step of conversion of OAA to malate and back again? why/why not
no; because cytosolic NADH is immediately produced in the first step of this pathway
GNG step 1, lactate predominant: now that lactate is converted to pyruvate, what happens
pyruvate is shuttled to the mitochondria and converted to OAA
GNG step 1, lactate predominant: once pyruvate is converted to OAA, what happens
OAA is directly converted to PEP in the mitochondria via a mitochondrial version of PEP carboxykinase
GNG step 1, lactate predominant: which enzyme converts OAA to PEP
PEP carboxykinase
GNG step 1, lactate predominant: once PEP is produced, what happens
PEP leaves the mitochondria
GNG step 8: what is the reagent and product
fructose 1,6-bisphosphate –> fructose 6-phosphate
GNG step 8: how is F6P produced
hydrolysis of the phosphate on the C1 of F1,6P
GNG step 8: which enzyme is used
fructose 1,6-bisphosphatase 1
GNG step 10: what is the reagent and product
glucose 6-phosphate –> glucose
GNG step 10: how is glucose made
hydrolysis of the phosphate of C6 on G6P
GNG step 10: what enzyme is used
glucose 6-phosphatase
GNG step 10: T or F: only liver hepatocytes, renal cells, and epithelial cells of the small intestine have glucose 6-phosphatase enzyme
true; other tissues are thus not able to complete GNG and must receive any GNG products by the bloodstream
