Macromolecule Metabolism Flashcards
Net reaction of glycolysis
Glucose + 2 NAD+ + 2 ADP + 2 P –> 2 Pyruvate + 2 NADH + 2 ATP + 2H + 2H2O
ATP-producing steps of glycolysis
1) 1,3-bisphosphateglycerate –> 3-phosphoglycerate (via phosphoglycerate kinase)
2) PEP –> pyruvate (via…)
via pyruvate kinase
If nothing else remember that the two kinases in payoff phase produce ATP
Hexokinase: Involved in which pathway, what step does it catalyze, why is it important
Pathway: glycolysis
Catalyzes: glucose –> glucose-6-phosphate
Importance: FIRST rate limiting step in glycolysis and irreversible. High affinity/low Km for glucose. Uses ATP
Hexokinase regulation
Product inhibition: high glu-6-PO inhibits. Remember that Glu-6-PO is the product of hexokinase enzyme
Glucokinase: involvement in which pathway at what step and its significance in the pathway?
Pathway: glycolysis
Step: glucose –> glu-6-PO
Significance: “glucose sensor” only acts when there is a high amount of glucose. Low affinity/high Km for glucose.
Glucokinase regulation
NOT inhibited by product like hexokinase. Induced by insulin signaling. Also controlled by glucokinase regulatory protein: rapidly activates/deactivates glucokinase in the liver to ensure enough glucokinase.
When there are low levels of glucose, glucokinase does not need to be expressed and is sequestered in the nucleus
What other pathways can glucose-6-phosphate be used in? (2)
- Gluconeogenesis
2. Pentose Phosphate Pathway (HMP Shunt)
Phosphofructokinase-1: involvement in which pathway at what step and its significance in the pathway?
Pathway: glycolysis
Step: fructose-6-phosphate –> fructose 1,6-bisphosphate (uses ATP)
Significance: catalyzes the committed step of glycolysis.
Phosphofructosekinase-1 regulation
Local and hormonal factors: Inhibited by: -High ATP -Citrate -Glucagon Activated by: -Fructose-2,6-bisphosphate (activates PFK-1) -High ADP -Insulin
Pyruvate kinase: involvement in which pathway at what step and its significance in the pathway?
Pathway: glycolysis
Step: PEP –> pyruvate
Significance: ATP production step. Transfers PEP to pyruvate. Last step of glycolysis. Pyruvate can be used for many things
Glycolysis occurs where in the cell
Cytoplasm
Pyruvate kinase regulation
Activated: F-1,6-BP (product produced by PFK-1)
Inhibited: ATP, Alanine
What enzyme does alanine inhibit and why?
Alanine inhibits pyruvate kinase, the enzyme that converts PEP to pyruvate. Alanine synthesized from pyruvate, high levels of alanine signal that no more pyruvate is needed. Pyruvate kinase controls the conversion of PEP to pyruvate
What is the mechanism for energy production under anaerobic conditions?
Pyruvate converted into lactate via lactate dehydrogenase. Important cofactor NADH. Converted into NAD+
Where in the cell does gluconeogenesis occur?
Begins in the mitochondrial matrix because of pyruvate but mostly occurs in the cytosol
Pyruvate carboxylase: involvement in which pathway at what step and its significance in the pathway?
Pathway: gluconeogenesis
Step: mitochondrial pyruvate –> mitochondrial oxaloacetate
Significance: pyruvate can not cross mitochondrial membrane and it must be converted to oxaloacetate which is facilitated by pyruvate carboxylase. Uses ATP
PEP carboxykinase: involvement in which pathway at what step and its significance in the pathway?
Pathway: gluconeogenesis
Step: oxaloacetate –> phosphoenolpyruvate
Significance: Uses GTP, using oxaloacetate that was converted from pyruvate in the mitochondrial matrix and oxaloacetate was moved to the cytosol, converts to phosphoenolpyruvate to continue gluconeogenesis
Fructose-1,6-bisphosphatase: involvement in which pathway at what step and its significance in the pathway?
Pathway: gluconeogenesis
Step: fructose-1,6-bisphosphate –> fructose-6-phosphate
Significance: counterpart to PFK-1. Also the committed step
Fructose-1,6-bisphosphate regulation
Occurs only in gluconeogenesis. Counterpart of PFK-1. Opposite activators and inhibitors. Activators: -High ATP -High citrate -High glucagon Inhibitors: -High ADP -High insulin -High fructose-2,6-bisphosphate
Glucose-6-phosphatase: involvement in which pathway at what step and its significance in the pathway?
Pathway: gluconeogenesis
Step: glucose-6-phosphate –> glucose
Significance: catalyzes end goal to make glucose
Glycogen synthase/glycogen phosphorylase: involvement in which pathway at what step and its significance in the pathway? Regulated by?
Pathway: glycogen synthesis/glycogenesis and glycogen breakdown/glycolysis respectively
Step:
Significance: Both involved in the rate limiting step of glycogen synthesis or break down
Regulation: allosteric and hormonal
-high ATP: activates glycogen synthesis
-epinephrine and glucagon: activates glycogen breakdown
-insulin: activates glycogen synthesis
Where does Kreb Cycle occur within a cell
Mitochondrial matrix
Pyruvate dehydrogenase complex: involved with which pathway, what step does it catalyze, what is its significance?
Pathway: Krebs Cycle
Step: Pyruvate –> Acetyl-CoA
Significance: Has 3 enzymes and 5 cofactors including NAD+ and important as it commits pyruvate to Krebs Cycle (irreversible)
Pyruvate dehydrogenase complex regulation
Regulated by 2 enzymes:
- PDH kinase: phosphorylates PDH making it inactive
- PDH phosphorylase: dephosphorylates PDH making it active
Also allosteric regulation: Inhibited by: -ATP -Acetyl-CoA -NADH
Citrate synthase: pathway involvement, steps involved, significance, regulation?
Pathway: Krebs
Steps: oxaloacetate + Acetyl-CoA –> citrate
Significance: Irreversible
Regulation: inhibited by ATP
Isocitrate dehydrogenase: pathway involvement, steps catalyzed, significance, regulation
Pathway: Krebs cycle
Steps catalyzed: isocitrate –> alpha ketoglutarate
Significance: rate-limiting step, produces NADH
Regulation: inhibited by NADH and ATP
Note: dehydrogenase means it involves a redox rxn. Often times NAD/NADH
Alpha ketoglutarate dehydrogenase: pathway, step catalyzed, significance, regulation
Pathway: Krebs
Step catalyzed: alpha ketoglutarate to succinyl-CoA
Significance: rate limiting step, produces NADH
Regulation: inhibited by high ATP, NADH, and succinyl-CoA
Why are isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase rate limiting enzymes?
Through allosteric binding these enzymes can increase or decrease affinity between enzyme and substrate and therefore control the rate of Krebs cycle
Guanosine triphosphate and succinate dehydrogenase produce what key cofactors?
Wouldn’t worry too much but on the off chance
Guanine triphosphate: GTP
Succinate dehydrogenase: succinate –> fumarate produce FADH2
TCA intermediates that are precursors to other cycles: what are the intermediates and what are the cycles?
Acetyl-CoA: Lipid synthesis
Alpha-ketoglutarate: Amino acid synthesis
Which pathway does not involve ATP
Pentose phosphate pathway
Where does the pentose phosphate pathway take place
Cytosol
Which pathway produces NADPH
Pentose phosphate pathway
What is the purpose of the pentose phosphate pathway?
To make ribose-5-phosphate (key intermediate of RNA/DNA synthesis) and NADPH high energy molecule
What is the important enzymes of PPP? (Relevance?)
glucose-6-phosphate dehydrogenase
6-phosphogluconate dehydrogenase
NADP+ dependent enzymes
Goal of the electron transport chain:
Couple energy stored from electron acceptors and proton gradient to generate ATP
Where does the electron transport chain/oxidative phosphorylation occur?
Mitochondrial innermembrane
What cofactor is associated with Complex I of the electron transport chain and what is the complex’s role in the proton gradient?
NADH gives electrons to Complex I.
Is involved in proton gradient. Every electron moves 2 protons, therefore 4 protons are pumped into the intermembrane space
What cofactor is associated with Complex II of the electron transport chain and what is the complex’s role in the proton gradient
FADH2 cofactor
Not involved w/ proton pumping
Where does Complex III of the ETC get its electrons from? Does Complex III contribute to the proton gradient?
Receives electrons from both Complex I and Complex II. Both complexes shuffle electrons through CoQ and CoQ charges complex III, 2 electrons at a time. Yes, net 2 electrons move 4 protons into intermembrane space
Where does Complex IV receive its electrons and does it contribute to the proton gradient?
Receives 2 electrons from cytochrome C and does contribute to the proton gradient. Contributes 2H+
Final electron acceptor of ETC? How does the mechanism work?
O2 final electron acceptor. O2 splits into 2 oxygen molecules and both oxygens accept hydrogens making 2 water molecules H2O. High yield :)
How does the oxidative phosphorylation ultimately create ATP from ADP? What role does ATP synthase play?
Complex V uses the proton gradient created from complexes I-IV to drive conversion of ADP –> ATP. ATP synthase’s F1 component has 3 conformations: open-ADP + Pi enters
Loose: substrate in active site
ATP produced as active site moves from loose to tight
Tight: ATP product bound
Open: ATP released into matrix
For every complete turn of ATP synthase, 1 ATP molecule is produced
What are the pathways linked to glucose-6-phosphate?
Glycolysis
Gluconeogenesis
PPP
Amino acids that are only ketogenic?
Lysine and leucine
Essential amino acids?
PVT TIM HaLL
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Lysine, Leucine
Class of enzymes responsible for maintaining amino acid homeostasis?
Aminotransferase/transaminases
EX: aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
If ammonia levels are too high what amino acids become depleted?
Alpha-ketoglutarate and then glutamate
Maple Syrup Urine Disease. Deficient enzyme? Amino acids involved?
Enzyme: alpha-ketoacid dehydrogenase
Amino acids: isoleucine, leucine, valine
I Love Vermont Maple Syrup
Propionic Aciduria. Enzyme deficiency? Amino acids involved?
Enzyme: propionyl-CoA carboxylase
AAs: valine, methionine, isoleucine, threonine
Accumulate propionyl-CoA
VOMIT
Valine (Odd fatty chain acids) Methionine Isoleucine Threonine
Classic PKU v Atypical PKU
Classic PKU: deficiency in phenylalanine hydroxylase, inability to convert phenylalanine into tyrosine. Phenylalanine –> phenylpyruvic acid giving patients musty smell
Atypical PKU: defective dihydropteridine reductase, presents similarly but with lower neurotransmitter levels as well
Albinism caused by enzyme and what amino acids?
Deficient tyrosinase enzyme, responsible for producing melanin from tyrosine.
What nonessential amino acid is essential for PKU patients?
Tyrosine because deficient enzyme cannot convert phenylalanine to tyrosine so they must ingest in diet
Homocystinuria caused by what two enzyme deficiencies?
Methionine synthase or cystathionine beta synthase
Where does fatty acid oxidation/beta oxidation occur within the cell?
Mitochondrial matrix
How does LCFA cross into the mitochondrial membrane?
Via the carnitine shuttle. Carnitine acyltransferase-1 converts fatty acyl-CoA to fatty-acyl carnitine. Then carnitine acyltransferase-2 converts the fatty acyl carnitine back to fatty acyl-CoA
CARnitine for CARnage of fatty acids
What two high energy molecules are produced during fatty acid oxidation?
FADH2 and NADH
End product for even numbered fatty acids? End product for odd numbered fatty acids? Of beta oxidation
Even: Acetyl-CoA enters TCA
Odd: Propionyl-CoA carboxylated to form succinyl-CoA and enter the TCA
Where does synthesis of fatty acids occur?
Cytosol
What is the precursor for fatty acid synthesis and how is it brought in?
Acetyl-CoA precursor brought in via citrate shuttle from the matrix –> cytoplasm
Carnitine acyltransferase-1: pathway, step, regulation?
Pathway: fatty acid oxidation/beta oxidation
Step: acetyl-CoA to malonyl-CoA
Regulation: inhibited by malonyl-CoA (intermediate of fatty acid synthesis)
also note: fatty acyl-CoA SYNTHETASE is part of beta oxidation NOT fatty acid synthesis
Acetyl-CoA carboxylase (ACC): pathway, step, regulation?
Pathway: fatty acid synthesis Step: acetyl-CoA --> malonyl-CoA Regulation: regulated locally and hormonally Inhibition: -Palmitoyl-CoA (product of fatty acid synthesis) -AMP kinase (phosphorylates ACC) -Glucagon and epinephrine Activation: -Citrate (precursor) -Insulin
What high energy molecule is consumed during fatty acid synthesis?
NADPH
Which organ creates ketones and where are the ketone bodies sent?
Liver converts fatty acids to ketones and sends them to the muscle and brain for energy
Diabetic ketoacidosis causes fruity breath through what mechanism?
Excess breakdown of triglycerides and fatty acid oxidation. Ketoacids converted to acetone to produce fruity breath odor
The rate limiting enzyme of purine de novo synthesis and where does the derivative come from?
5-phosphoribosyl-1-pyrophophate) PRPP and formed from ribulose-5-phosphate made from the PPP/HMP shunt
Gout caused by presence of _____ from what pathway?
Caused by excess uric acid from purine synthesis pathway
Intermediates of urea cycle:
Citrulline, Aspartate, Arginosuccinate, Fumarate, Arginine, Urea, Ornithine, Carbomoyl (CPS I)
Ordinarily, Careless Crappers Are Also Frivolous About Urination
What is the precursor of mineralocorticoids, vitamin D, and bile acids?
Cholesterol!! Also the precursor of: glucocorticoids and androgens
HMG-CoA reductase: pathway, step catalyzed, importance
Pathway: cholesterol
Step catalyzed: HMG-CoA –> mevalonate
Importance: rate-limiting enzyme of cholesterol pathway, uses NADPH
Also know the other key intermediate in cholesterol: squalene
What enzyme is the target of statin drugs?
HMG-CoA reductase of cholesterol synthesis. Used to control hyperlipidemia
Role of chylomicrons
Deliver triglycerides and cholesterol from INTESTINES –> BLOODSTREAM
Role of VLDL
Delivers lipids made in liver via endogenous pathway to the tissues
Role of IDL
Delivers lipids made in liver via endogenous pathway to the tissues
Role of LDL
Delivers cholesterol to tissues. Known as “bad cholesterol”. Cholesterol uses LDL receptors
Role of HDL
Delivers cholesterol to the liver from the tissues. Known as good cholesterol
What happens to excess cholesterol?
Brought back to the liver to be converted into bile acid
HMG-CoA synthase: pathway, step catalyzed, importance
Pathways: cholesterol, ketogenesis
Step catalyzed: eh
Importance: know that it is associated with cholesterol synthesis and is the rate limiting step of ketogenesis
Carbamoyl phosphate synthetase II: pathway, step catalyzed, importance
Pathway: pyrimidine synthesis
Step: glutamine + CO2 –> carbamoyl phosphate
Importance: rate limiting step of pyrimidine synthesis, not to be confused with its isomerase carbamoyl phosphate synthetase I of the urea cycle in the mitochondria
