MMT: gluconeogenesis Flashcards
Describe the physiological significance of gluconeogenesis. List the primary precursors of gluconeogenesis
Helps us generate glucose to use for energy from non-carbohydrate sources, namely pyruvate, lactate, glucogenic amino acids, and glycerol
Gluconeogenesis starts in the ___ and ends in the ___
Mitochondria; endoplasmic reticulum
Name the major organs that carry out gluconeogenesis. Locate the various enzymes of gluconeogenesis in cell compartments
Liver and kidney cortex
High glucagon stimulates ___ (gluconeogenesis vs glycolysis)
Gluconeogenesis
high insulin stimulates ___ (gluconeogenesis vs glycolysis)
glycolysis
High cortisol stimulates ___ (gluconeogenesis vs glycolysis)
Gluconeogenesis
Generally, diabetes type 1 or 2 stimulates ___ (gluconeogenesis vs glycolysis)
gluconeogenesis
Specify how we can make DHAP, oxaloacetate, and pyruvate to act as starters in gluconeogenesis
DHAP: glycerol
Oxaloacetate: some amino acids
Pyruvate: lactate and some amino acids; whole pathway will be used
discuss how alcoholism can inhibit gluconeogenesis and lead to hypoglycemia
sustained ethanol concentration requires constant use of NAD+ to process it, forming a lot of NADH and not much NAD+. The lack of NAD+ and abundance of NADH drives formation of lactate as opposed to pyruvate, and makes alanine convert to lactate instead of pyruvate. As a result, these cannot enter gluconeogenesis and hypoglycemia can happen
Describe how glycerol becomes DHAP
Glycerol uses glycerol kinase > glycerol phosphate, uses glycerol phosphate dehydrogenase > DHAP
Describe how asparagine enters gluconeogenesis
Asn uses asparaginase > aspartate, uses transaminase > oxaloacetate
Describe how lactate enters gluconeogenesis
Lactate uses lactate dehydrogenase to form pyruvate, or alanine uses alanine aminotransferase to become pyruvate
Name the enzymes and reactions that replace pyruvate kinase in gluconeogenesis
Pyruvate +Pyruvate carboxylase (uses biotin) > OAA
OAA + PEP carboxykinase (decarboxylation and phosphorylation) > PEP
describe the structure of pyruvate carboxylase
ATP grasp domain, allosteric domain, and carboxylase transferase domain, biotin transfer domain
PEP carboxykinase: reaction is catalyzes, glycolytic enzyme it replaces, energy source,
OAA > phosphoenol pyruvate
replaces
Pyruvate kinase
Decarboxylation and phosphorylation
Name the enzyme and reaction that replaces PFK. does it produce ATP?
F1,6BP + fructose 1,6 phosphatase > F6P
Allosterically regulated
Does not produce ATP
___ drives unfavorable reactions
Decarboxylation
Name the enzyme and traction that replaces hexokinase
G6P + glucose-6-phosphatase > glucose
Does not produce ATP
Pyruvate carboxylase is a ___ enzyme
Mitochondrial
Specify the source of energy used for gluconeogenesis.
ATP from fatty acid beta oxidation, TCA and oxidative phosphorylation
Describe the coordinated control of the enzymes in glycolysis and gluconeogenesis.
-High fructose 2,6 biphosphate can activate PFK (glycolysis) and inhibit fructose 1,6 bisphosphatase (gluconeogenesis)
-largely regulated by high vs low energy charge; things like ATP, acetyl CoA, and citrate signal high energy charge (less glycolysis, more gluconeogenesis) and low energy charge signals glycolysis
what would happen if we ran glycolysis and gluconeogenesis at the same time
Cells in the muscle may run glycolysis at the same time as gluconeogenesis runs in the liver. Glucose enters the muscle form the blood, converts to pyruvate then lactate. Lactate enters the blood then the liver, then becomes pyruvate and then glucose. Cycle starts again.
describe hypolactasia
lack of lactose. discomfort, bloating, diarrhea
what is galactosemia? what is the treatment?
Unable to break down galactose
treatment is avoiding lactose
describe classic galactosemia: deficiency type, symptoms
type 1; galactose-1-phosphate (GALT) deficiency.
Delayed growth, jaundice, lethargy, eventual cataracts, renal failure, developmental delays, risk of E coli sepsis
describe non-classic galactosemia: deficiency type and symptoms
type 2; galactokinase (GALK) deficiency.
Cataracts and risk of E coli sepsis. Less severe as it is the first enzyme used in galactose processing.
what is deficient in type 3 galactosemia
GALE
describe fructoseria: what enzyme is deficient and what are the symptoms
fructokinase deficiency; fructose in the urine but otherwise asymptomatic
describe Hereditary fructose intolerance: what is deficient, what is happening, what are the symptoms, treatment
aldolase B deficiency. More severe because the phosphate is trapped on the molecule.
Poor feeding, jaundice, hyperglycemia. Avoid fructose or sucrose.
which is the more severe galatosemia? why?
classic galactosemia (GALT). GALk is the first enzyme used in processing galactose and thus it being deficient causes less severity.
which is the more severe fructoseria? why?
aldolase B deficiency (hereditary); the phosphate molecule gets trapped.
which gluconeogenesis associated condition(s) result in increased risk of E coli sepsis?
galactosemias
what pathology is associated with symptoms appearing after eating fruits or drinking fruit juices?
aldolase B deficiency
aldolase B deficiency leads to ___glycemia (hypo vs hyper)
hypoglycemia
which two pathologies are associated with jaundice?
classic galactosemia (GALT) and aldoase B deficiency
deficiency in converting fructose to fructose-1-phosphate results in ___
essential fructosuria
what is the other enzyme associated with galactokinase?
aldose reductase
a buildup of F1P is indicative of ___
aldoalse B deficiency
