Metabolism Flashcards
What is the carboxylation rxn of pyruvate to OAA in gluconeogenesis called and what are the two steps?
anapleurotic rxn
1) activation of CO2 by biotin (B7) cofactor of pyruvate carboxylase complex
2) transfer of co2 group from the biotin cofactor to methyl group of pyruvate
Complex II in electron transport chain
oxidizes FADH2 to FAD+, not enough power to pump H+, only electron transport complex that is entirely encoded by nuclear DNA (rest a mix between mitochondrial and nuclear DNA); gets FADH2 from rxn in TCA where succinate is converted to fumerate (makes FADH2 because not enough reducing power to make NADH, FADH2 is next best thing) ; shunted to complex two when moving NADH across mito in muscles as part of the G3P shuttle
What other compound is needed to activate biotin/Co2 complex?
acetyl coA; high level of acetyl CoA tell body it needs more OAA;
if ATP is in surplus; OAA goes to glucose (i.e the pyruvate carboxylase is activated)
if ATP is deficient; OAA condenses with acetyl CoA to stop the gluconeogenesis pathway
What is reduced and what is oxidized in the pyrvate –> PEP rxn?
1.) OAA is reduced to form malate; NADH is oxidized to NAD+ in cytosol
2.) malate is oxidized to OAA; NAD+ is reduced to NADH in mitochondria
OIL RIG
What does phophoenol pyruvate carboxykinase do?
decarboxylates and phosphorylates OAA to PEP
Is the delta G of pyruvate to PEP + or -?
slightly net positive, it is the coupling of the carboxylation decarboxylation rxns that make the net rxn go
Where do the rxns of gluconeogenesis occur?
pyruvate to PEP occurs in mitochondria (part of it)
F16 BP to F6P occurs in the cytosol
G6P to Glucose occurs in the cytosol
powered by enzymes that are unique to gluconeogenesis
Regulation of forward and back rxn of F16BP, F6P
Glycolysis: F6P –> PFK F1,6 BP ( activated by AMP, F26BP,; inhibited by citrate, ATP (high levels of fuel and energy))
Gluconeogenesis : F16BP–> F16BPhosphotase F6P (activated by citrate; inhibited by AMP, F26BP; )
high levels of fuel and energy, gluconeogeneis; low levels of fuel and energy, glycolysis
PEP to Pyruvate Regulation
Pyruvate Kinase: inhibited by ATP, alanine, ; activated by F16 BP
Pyruvate carboxylase: activated by acetyl coA, inhibited by ADP
PEP kinase: inhibited by ADP
What is the role of NADPH in body?
primary reducing power in biosynthesis (esp sterols and fatty acids)
What are the five different possible pentose pathways based on body’s energetic and molecular needs?
1) When there is an increase in NADPH: NADPH inhibits G6P dehydrogenase; rate of G6P entry into pathway slowed
2) When the demand for NADPH is much higher than ribose 5 phosphate: make 2 NADPH via ox part of pathway, convert ribolose 5 phosphate back G6P
3) When there is a high demand for NADPH and ATP: make NADPH via ox part of PPP; use ribose 5 phosphate to make G3P and F6P via non ox part of pathway
4) When two molecules of NADPH are sufficient: make NADPH via ox part of shunt
5) When you need DNA/RNA precursors but not NADPH-> make G3P and F6P via glycolysis and then shunt them through the non ox part of the PPP pathway to make ribose 5 phosphate
What are the two precursors for G3P and F6P in the non ox part of the PPP?
ribose 5 phosphate and xylulose 5 phosphate (2 transketolase rxns, 1 transaldolase )
What is glycogen?
stored glucose that can be rapidly mobilized to maintain blood glucose (dietary glucose is variable and gluconeogenesis is slow); stored in liver and muscle, liver can maintain blood glucose for 10-18 hrs
What is normal blood glucose?
80-120 mg/dL
What determines whether glycogen in being synthesized or broken down?
Rate of anabolism or catabolism, glycogen is constantly being both synthesized and broken down into glucose
What are the enzymes that synthesize glycogen from glucose and why are there two?
glycogen synthase adds glucoses to form 1,4 bonds (active when dephosph)
branching enzymes (4,6 transferase) add 1,6 alpha bonds
different bonds, different enzymes
What is the function of glycogenin in glycogen metabolism?
Glycogen synthase will only add to the non reducing ends of glycogen molecules a couple residues long so glycogenin catalyzes the addition of the first few glucose molecules (primer)
limit dextrin
4 glucose residues on a chain is the smallest size chain that glycogen phosphorylase can break down at this pt, glucontransferase moves three glucose from a branch onto glucose chain and phosphorylase can work; last glucose on branch is removed by a 16 glucosidase
What are the three non hormonal regulations/sensors of glucose and where are they located?
liver
1) phosphorylated phophorylase a (active) also binds PP1 and deactivates it so get glycogen breakdown and no glycogen synthesis
2) Glucose binds to phosphorylated phosphorylase a dephosphorylates it, thus decreases glycogen breakdown with high glucose
3) When glucose dephos phosphorylase, phosphorylase also releases PP1 which dephosphorylates glycogen synthase and activates creation of glycogen
Why does calcium partially activate phosphorylase?
binds of a subunit on phosphorylase kinase (one of four) so partially activates phosphorylase kinase that can phosphorylate phosphorylase at a low level, so that as muscles contract, there is an increase in glucose available
Glucagon and epi signaling pathway
glucagon binds to trimeric G protein receptor in plasma membrane of liver (released by a cells on pancreas) ; Gas, releases Ga that binds and activates AC activate cAMP activates PKA ; phosphorylates phosphorylase and activates it ; also phosphorylates PFK2 and PF26BPase which activates PF26BPase and deactivates PFK2, decreasing the amt of F26BP which decreases glycolysis (inhibits PFK) and increases gluconeogenesis (activates F16BPhosphotase)
epi has same pathway except in muscles and is release by adrenal medulla or post ganglionic sympathetics
What is the insulin pathway?
Insulin is release by B cells in pancreas in response to high glucose, binds to a transmembrane receptor and activates PP1 which dephosphorylates glycogen synthase(activates) to make glycogen and dephos phosphorylase which inactivates the glycogen metabolism pathway
What are the enzymes involved in glycogen catabolism
glycogen phosphorylase transferase a 1,6 glucosidase glucophosphomutase G6 phosphotase
What are the three ketone bodies made from acetyl coA in liver?
3 hydroxybuterate, acetoacetate, acetone
ketone bodies are transportable forms of acetyl coA used when carb availability is low
in, e.g braine acetoacetate –> 2 acetyl coA (thiolysis)
