MCM Day 2-End Flashcards
which cells carry out glycolysis?
all cells
most common fuel for glycolysis
fructose and galactose
what is de novo synthesis
gluconeogenesis in liver
why can glucose cross membrane so what does it use
is polar, needs GLUT
GLUT 1 GLUT2 GLUT3 GLUT4 what is unique about each waht is insulin dependent affinity? regulated?
GLUT 1 - ubiquitous but high in RBS;s. high affinity - Glut2 - main transporter in liver - low afinity GLUT3 maintranspoter in neurons - high afinity Glut 4 - present in skelatal muscle heart - adpoose tissue - insulin dependent - only one regulatedf
what type of lipid makes up the lipid rafts
cholesterol make up the lipid rafts
where is glut4 sequestered
vesicles
what is put in and what are the products of glycolysis
1 glucos in 2 molecules pyruvate out generates 2 atp net 2 NADH
what are the 5 steps of glycolysis that are important. what are the enzymes that are used and what are the products
- Glucose+ATP = glucose 6 phosphate hexokinase/glucokinase (in liver) 3. Fructose6phosphate+atp= fructose 1,6 bisphosphate. pfk1 used. 6. glyceraldehyde 3 phasphate + P +NAD = 1,3 bisphosphoglycerate. G3-P dehydrogenase 7. 1,3 BPG = 3-PG makes ATP phosphoglycerate kinase 10. Phosphenolpyruvate to pytuvate makes atp - pyruvate kinase
3 irriversible phosphoylation steps use which enzymes. eavily influenced by which 2 things. what are the others
hexokinase/glucokinase phosphofructokinase-1 (pfk-1) pyruvate kinase insulin and glucagon ATP, AMP, glucose
how is glucokinase different from hexokinase
glucokinase - low afinity v max high not inhibited by G6P
what is the rate limiting step and what does it convert to waht? what activates it
prk-1. F6P to F1,6BP AMP, F2,6BP PFK2 makes more F26BP. which leads to more PFK1
How does affect does glucagon and insulin have on PFK1
High insulin dephosphorylates PFK-2/FBPase-2. makes F2,6BP which activates PFK-1 High glucagon activates protein kinase A, phosphoralates PFK-2/FBPase-2, reduces PFK-1 Activity
How do insulin and glucagon affect pyruvate kinase. what else affects pyruvate kinase and how
high insulin causes protine phosphatasewhich activates pyruvate kinase high glucagon increases cAMP, which incrases protin kinase which decreases pyruvte kinase alanine inhibits
what are the fates of glucose-6-phosphate
precurosor for Pentose phosphate pathway (becomes ribose and NADPH) glucose pyruvate glycogen
fates of pyruvate, and conditions under why each would happen
lactate, when NADH is needed] Oxidized in TCA cycle to Acetyl CoA then CO2 when ATP is needed Alanine for gluconeogenesis fed state or protein synthesis Converted to ethanol. yeast and stuff
What happens to glycolysis when pyruvate kinase is defective
causes hemolytic anemia. MOST DISORDERS CAUSE THIS
Why are disorders in glycolsis so detrimental to RBC’s and what are the adverse affects
they dont have mitochondia, this is their only source of ATP ATP shortage leads to disruption of ion gradients powered by ATP leads to hemolytic anemia
Why are disorders in glycolsis so detrimental to the brain and what are the adverse affects
glucose is the only source of energy that can cross the blood brain barrier brain has to resort to keton bodies or glucose fron liver in starvation
what characterizes diabetes as a whole. what cells are affected to cause diabetes types 1 and 2 what are potentail causes?
hyperglycemia characterizes diabetes type one is loss of pancreatic B cells type 2 is loss of funciton of B cells causes: trauma, infections, cancer, all sorts of stuff. mutaions in GK and mitochondrial tRNA leu gens.
what is hemolitic anemia what causes it
when there is premature destruction of rbs many things cause it. infections, inhereted defects, nutritional deficeniceis
what disease does a deficient PFK-1 cause what characterizes this
Tarui disease least common GSD excersied induced muschle cramps and weakness hymolytic anemia juandice
how much glucose does the body need per day and how much does the brain need. how much available from glycogen
160 g per day 120 g for brain 20 present in body fluids 190 availabe from glycogen have enough in store for 1 day
where does gluconeogenisis occur, what are the precurosrs
occurs in liver, kidney and small instestine lactate, amino acids and glycerol
what are the steps of gluconeogdenesis and the enzymes it uses to bypas the 3 irrivirsible steps of glycolysis?
pyruvate to OAA, uses Pyruvate carboxylase OAA to Posphoenolpyruvate (PEP) uses PEP carboxykinase Fructose 1,6 -BP to Fructos 6-P uses Fructose 1,6-bisphosphatase Gructose 6P to glucose Glucose-6 phosphatase Named for what it sated out as, except the second one
what are the enzymes in glycolosys with their correspoining gluconeogenesis enzymes that get around them
hexokinase/glucokinase - Glucose -6 phosphatse PFK1 - fructose1,6- bisphosphatase PK - Phosphoenolpyruvae (PEP) carboxykinase and Pyruvate carboxylase
regulation of of gluconeogenesis first step
- pyruvate corboxylase (PC) mitochondial enzyme, biotin is cofactor. CO2 dependent.
what hepes to gtaet oxaloacatete of of mitochondia
converted to malate through malate dehydrogenase, then leaves and converted back
rate limiting step of gluconeogenesis, regulation of last step regulation of other step that circumvents irrivirsible step of glycolysis
fructos 1,6 bisphosphatase -rate limiting -activates : cortisol and citrate -inhibited: AMP and F26BP Glucose 6-Phosphatase -dephosphoraltion to make glucose -activated by cortisol, only in liver, kidneys, SI and pancreas PEP carboxykinase (CK) - transcription activated by cortisol, glucagon, thyroxine
where does glucose 6- phosphatase operate? How does G6P get to the ER
in the lumen of the ER G6P transporter
Cori Cycle links what to what
links lactate from anaerobic glycolysis in RBS and convertes it back to glucose through gluconeogenesis in the liver
precursors or gluconeogenesis
carbs, lipids, protiens fructose, galactose glycologen, glycerol propionate lactate alanine amino acids
Glycerol, propionate, alaine and amino acids are precurors of gluconeogenesis, what are theri sources and points of entry
glycerol - source - lipid degredation - enters - DHAP via phosphorylated glycerol intermediate propionate - source is degradation of odd numbered fatty acid - enders - TCA cycle intermediate converted to malate alaine - source, easy enter - pyruvate amino acid - TCA cyle intermeida for amino acid entry
Von Gierke disease
Dificeincey in glucose 6-phosphatase. can’t regenerate that glucose
What are GLUT5 and SGLT1 responsible for what in the blood cell
GLUT5 - fru uptake SGLT1 - Gal/Glc Na
What is Fanconi-Bickel syndrome, what is it
Glut 2 defect. (mutations) cant bring in Glactose, fructose, glucose autosomal recessive disorder fasting hypoglycemia and postprandial hyperglyemia
how to get from glucose to fructose
glucose reduces to sorbitol by aldose reductase frucose oxidized by sorbitol dehydrogenase.
where does sorbitol accumulate
kidney lens, retina, schwann cells
why can fructose be bad,
avoid PFK-1, rate limiting step. converted easily to fat
galactosemia what is it
deficient in glucose 1p uridyltransferase (GALT) Deficeincy in Galactokinase - accumulation of galactitiol in lense of eye, leads to cataracts in early life
What is the purpoose of the PPP. where does it occur? what gets converted to what
make sugars for DNA and RNA formation makes NADPH no energy produced occurs in cytosol oxidation of G6P to ribulose 5-P
PPP oxidative phase what is being oxidized what is the rate limiting step, what happens with defienceny of the rate limiting enzyme what is regenerated and what is regenerated by?
oxidation of G6P G6P dehydrogonase is the rate limiting step. produces NADPH G6P dehydrogenase deficiency causes hemolytic anemia NADPH regenerates gutathionie
PPP Oxidative phase 3 steps
Oxidation of G6P, to 6-phosphoglucono lactone lactone to 6- phosphogluconate 6-phosphogluconate to ribulose 5P
PPP non oxidative whatcha need to know
reversible end products shunt to glycolytic, gluconeogenic or nucleotide synthesis pathways
When is the PPP needed
when there is a high demand for ribose 5P, when cells are rapildy dividing WHen there is a high demand for NADPH - non oxidative producs channeled inot gluconeogenesis for re-entry into PPP
branching and links of glycogen non reducing vs reducing end what is glycogenin, what purpose does it serve
branching is a-1,4 glycosidic bonds a-1,6 glycosidic bonds for branching non-reducing ends each gontain a terminal glucose with a free hyrdoxly group at carbon 4 reducing end consists of clucose monomer connectd to a protein called glycogenin glycogenin on reducing ends. is primer for more glycogen to be added
how and where is glycogen stored
liver muscle in granuales. granules also conatin enzymes needed for glycogen metabolism
liver glycogen vs muscle glycogen what does this mean in terms of glucagon
liver - regulates blook glucose levels muscle - provides resivoir of fule glucose for physical activity glucagon does not act on muscle
stargint with glucose, what is the initial pathway to glycogenesis what are the first 3 enzymes
glucose to G6P (hexokinase)(glucokinase) G6P to G1P (Phosphoglucomutase) G1P to UDP-Glucose (UDP-glucose prrophosphorylase)
Glycogenesis enzyme that elonges
glycogen Synthase (GS)(RATE LIMITING)
branching enzyme of glycogenesis
glucosyl (4:6) transferase
two major steps of gycogenolysis 1, shorteing . name of shorteing enzyme cofactor? 2? enzyme used? name of de-branching enzyme
- glycogen phosphorylase (GP) cofactor-vitamin B6 2. transferer. transferase debranching enzyme is the name
ration of glucose and G1P generated
10-1
Lysosomal glycogenolysis is a thing disease that happens when you cant?
small amount. Prompe disease
fate of glu1P in liver vs muscle
in liver can go back to GLU 6 P suinging glucose 6 phosphatase in muscles cant go to GLU-6-P so it is used in glycolysis and TCA Cycle
regulations steps for 1. glucogenesis 2. glycogonlysis what regulates both? when is each activive
- synthase 2. phosphorylase synthase active when dephosphorylated phosphorylation active when phosphorylation
regulation by insulin 4 key proteins involved in signaling cascake
Glut4 Protien kinase b (PKB) protein phosphatase 1 (PP1) glocogen synthase Kinase 3 (GSK3) Insulin activates PKB PKB activates PP1 PKB deactivates PP1 activates glycogen synthase, PP1 deactivtes glycogen phosphorylase
Type 2 blood levels
70-100 normal fed <140 100-125 pre fed >140 125+ diabetus fed >199
regulation of glycogenolysis signaling cascade key enzyme and second messengers
g Protein adenylate cyclase (AC) and cAMP Protein kinas A (PKA) Prtein phosphotase 1 (PP1) Phosphorylase Kinas (PK) Glucagon to receptor turns on G protein Activates AC which froms cAMP activates PKA phosphorylates GS (inactivating itn phosphroylates PK (activates) PK phosphorylat3es GP
GSD 0 enzyme, pathway effected
glycogen synthase deffective
CORI disease ENzyme pathwaye effected
a-1,6, glucosidase (debranching enzyme
Andersen disease
glucosyl 4:6 transferase branching enzyme
McArdle disease
glycogen phosphorylase breaking down glycogen
Hers Disease
liver glycogen phosphorylase
way to treat Pompe disease and what is it
defect in acid maltase (a-glucosidase) used in lysomal glycogen pathway accumuation of glycogen in lysosomes Enzyme replacement therapy - recombinant human a-glucosidase delivered via intravenous
Liver vs muscle glycogen phosphorylase mutations in each cause what disease what does AMP do to both
differ in sentsitivites to regultory molecules. mutations in liver cause HErs disease mutaions in muscle cause McArdle synderom Muscle activated by AMP Liver anaffected by AMP
