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Patient Presentation > Macromolecule Metabolism > Flashcards

Macromolecule Metabolism Flashcards

1
Q

Net reaction of glycolysis

A

Glucose + 2 NAD+ + 2 ADP + 2 P –> 2 Pyruvate + 2 NADH + 2 ATP + 2H + 2H2O

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2
Q

ATP-producing steps of glycolysis

A

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

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3
Q

Hexokinase: Involved in which pathway, what step does it catalyze, why is it important

A

Pathway: glycolysis
Catalyzes: glucose –> glucose-6-phosphate
Importance: FIRST rate limiting step in glycolysis and irreversible. High affinity/low Km for glucose. Uses ATP

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4
Q

Hexokinase regulation

A

Product inhibition: high glu-6-PO inhibits. Remember that Glu-6-PO is the product of hexokinase enzyme

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5
Q

Glucokinase: involvement in which pathway at what step and its significance in the pathway?

A

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.

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6
Q

Glucokinase regulation

A

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

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7
Q

What other pathways can glucose-6-phosphate be used in? (2)

A
  1. Gluconeogenesis

2. Pentose Phosphate Pathway (HMP Shunt)

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8
Q

Phosphofructokinase-1: involvement in which pathway at what step and its significance in the pathway?

A

Pathway: glycolysis
Step: fructose-6-phosphate –> fructose 1,6-bisphosphate (uses ATP)
Significance: catalyzes the committed step of glycolysis.

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9
Q

Phosphofructosekinase-1 regulation

A 
Local and hormonal factors:
Inhibited by:
-High ATP
-Citrate
-Glucagon
Activated by:
-Fructose-2,6-bisphosphate (activates PFK-1)
-High ADP
-Insulin
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10
Q

Pyruvate kinase: involvement in which pathway at what step and its significance in the pathway?

A

Pathway: glycolysis
Step: PEP –> pyruvate
Significance: ATP production step. Transfers PEP to pyruvate. Last step of glycolysis. Pyruvate can be used for many things

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11
Q

Glycolysis occurs where in the cell

A

Cytoplasm

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12
Q

Pyruvate kinase regulation

A

Activated: F-1,6-BP (product produced by PFK-1)
Inhibited: ATP, Alanine

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13
Q

What enzyme does alanine inhibit and why?

A

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

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14
Q

What is the mechanism for energy production under anaerobic conditions?

A

Pyruvate converted into lactate via lactate dehydrogenase. Important cofactor NADH. Converted into NAD+

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15
Q

Where in the cell does gluconeogenesis occur?

A

Begins in the mitochondrial matrix because of pyruvate but mostly occurs in the cytosol

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16
Q

Pyruvate carboxylase: involvement in which pathway at what step and its significance in the pathway?

A

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

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17
Q

PEP carboxykinase: involvement in which pathway at what step and its significance in the pathway?

A

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

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18
Q

Fructose-1,6-bisphosphatase: involvement in which pathway at what step and its significance in the pathway?

A

Pathway: gluconeogenesis
Step: fructose-1,6-bisphosphate –> fructose-6-phosphate
Significance: counterpart to PFK-1. Also the committed step

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19
Q

Fructose-1,6-bisphosphate regulation

A 
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
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20
Q

Glucose-6-phosphatase: involvement in which pathway at what step and its significance in the pathway?

A

Pathway: gluconeogenesis
Step: glucose-6-phosphate –> glucose
Significance: catalyzes end goal to make glucose

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21
Q

Glycogen synthase/glycogen phosphorylase: involvement in which pathway at what step and its significance in the pathway? Regulated by?

A

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

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22
Q

Where does Kreb Cycle occur within a cell

A

Mitochondrial matrix

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23
Q

Pyruvate dehydrogenase complex: involved with which pathway, what step does it catalyze, what is its significance?

A

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)

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24
Q

Pyruvate dehydrogenase complex regulation

A

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
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25
Q

Citrate synthase: pathway involvement, steps involved, significance, regulation?

A

Pathway: Krebs
Steps: oxaloacetate + Acetyl-CoA –> citrate
Significance: Irreversible
Regulation: inhibited by ATP

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26
Q

Isocitrate dehydrogenase: pathway involvement, steps catalyzed, significance, regulation

A

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

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27
Q

Alpha ketoglutarate dehydrogenase: pathway, step catalyzed, significance, regulation

A

Pathway: Krebs
Step catalyzed: alpha ketoglutarate to succinyl-CoA
Significance: rate limiting step, produces NADH
Regulation: inhibited by high ATP, NADH, and succinyl-CoA

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28
Q

Why are isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase rate limiting enzymes?

A

Through allosteric binding these enzymes can increase or decrease affinity between enzyme and substrate and therefore control the rate of Krebs cycle

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29
Q

Guanosine triphosphate and succinate dehydrogenase produce what key cofactors?

A

Wouldn’t worry too much but on the off chance
Guanine triphosphate: GTP
Succinate dehydrogenase: succinate –> fumarate produce FADH2

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30
Q

TCA intermediates that are precursors to other cycles: what are the intermediates and what are the cycles?

A

Acetyl-CoA: Lipid synthesis

Alpha-ketoglutarate: Amino acid synthesis

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31
Q

Which pathway does not involve ATP

A

Pentose phosphate pathway

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32
Q

Where does the pentose phosphate pathway take place

A

Cytosol

33
Q

Which pathway produces NADPH

A

Pentose phosphate pathway

34
Q

What is the purpose of the pentose phosphate pathway?

A

To make ribose-5-phosphate (key intermediate of RNA/DNA synthesis) and NADPH high energy molecule

35
Q

What is the important enzymes of PPP? (Relevance?)

A

glucose-6-phosphate dehydrogenase
6-phosphogluconate dehydrogenase
NADP+ dependent enzymes

36
Q

Goal of the electron transport chain:

A

Couple energy stored from electron acceptors and proton gradient to generate ATP

37
Q

Where does the electron transport chain/oxidative phosphorylation occur?

A

Mitochondrial innermembrane

38
Q

What cofactor is associated with Complex I of the electron transport chain and what is the complex’s role in the proton gradient?

A

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

39
Q

What cofactor is associated with Complex II of the electron transport chain and what is the complex’s role in the proton gradient

A

FADH2 cofactor

Not involved w/ proton pumping

40
Q

Where does Complex III of the ETC get its electrons from? Does Complex III contribute to the proton gradient?

A

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

41
Q

Where does Complex IV receive its electrons and does it contribute to the proton gradient?

A

Receives 2 electrons from cytochrome C and does contribute to the proton gradient. Contributes 2H+

42
Q

Final electron acceptor of ETC? How does the mechanism work?

A

O2 final electron acceptor. O2 splits into 2 oxygen molecules and both oxygens accept hydrogens making 2 water molecules H2O. High yield :)

43
Q

How does the oxidative phosphorylation ultimately create ATP from ADP? What role does ATP synthase play?

A

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

44
Q

What are the pathways linked to glucose-6-phosphate?

A

Glycolysis
Gluconeogenesis
PPP

45
Q

Amino acids that are only ketogenic?

A

Lysine and leucine

46
Q

Essential amino acids?

A

PVT TIM HaLL

Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Lysine, Leucine

47
Q

Class of enzymes responsible for maintaining amino acid homeostasis?

A

Aminotransferase/transaminases

EX: aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

48
Q

If ammonia levels are too high what amino acids become depleted?

A

Alpha-ketoglutarate and then glutamate

49
Q

Maple Syrup Urine Disease. Deficient enzyme? Amino acids involved?

A

Enzyme: alpha-ketoacid dehydrogenase
Amino acids: isoleucine, leucine, valine

I Love Vermont Maple Syrup

50
Q

Propionic Aciduria. Enzyme deficiency? Amino acids involved?

A

Enzyme: propionyl-CoA carboxylase
AAs: valine, methionine, isoleucine, threonine
Accumulate propionyl-CoA

VOMIT
Valine (Odd fatty chain acids) Methionine Isoleucine Threonine

51
Q

Classic PKU v Atypical PKU

A

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

52
Q

Albinism caused by enzyme and what amino acids?

A

Deficient tyrosinase enzyme, responsible for producing melanin from tyrosine.

53
Q

What nonessential amino acid is essential for PKU patients?

A

Tyrosine because deficient enzyme cannot convert phenylalanine to tyrosine so they must ingest in diet

54
Q

Homocystinuria caused by what two enzyme deficiencies?

A

Methionine synthase or cystathionine beta synthase

55
Q

Where does fatty acid oxidation/beta oxidation occur within the cell?

A

Mitochondrial matrix

56
Q

How does LCFA cross into the mitochondrial membrane?

A

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

57
Q

What two high energy molecules are produced during fatty acid oxidation?

A

FADH2 and NADH

58
Q

End product for even numbered fatty acids? End product for odd numbered fatty acids? Of beta oxidation

A

Even: Acetyl-CoA enters TCA
Odd: Propionyl-CoA carboxylated to form succinyl-CoA and enter the TCA

59
Q

Where does synthesis of fatty acids occur?

A

Cytosol

60
Q

What is the precursor for fatty acid synthesis and how is it brought in?

A

Acetyl-CoA precursor brought in via citrate shuttle from the matrix –> cytoplasm

61
Q

Carnitine acyltransferase-1: pathway, step, regulation?

A

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

62
Q

Acetyl-CoA carboxylase (ACC): pathway, step, regulation?

A 
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
63
Q

What high energy molecule is consumed during fatty acid synthesis?

A

NADPH

64
Q

Which organ creates ketones and where are the ketone bodies sent?

A

Liver converts fatty acids to ketones and sends them to the muscle and brain for energy

65
Q

Diabetic ketoacidosis causes fruity breath through what mechanism?

A

Excess breakdown of triglycerides and fatty acid oxidation. Ketoacids converted to acetone to produce fruity breath odor

66
Q

The rate limiting enzyme of purine de novo synthesis and where does the derivative come from?

A

5-phosphoribosyl-1-pyrophophate) PRPP and formed from ribulose-5-phosphate made from the PPP/HMP shunt

67
Q

Gout caused by presence of _____ from what pathway?

A

Caused by excess uric acid from purine synthesis pathway

68
Q

Intermediates of urea cycle:

A

Citrulline, Aspartate, Arginosuccinate, Fumarate, Arginine, Urea, Ornithine, Carbomoyl (CPS I)

Ordinarily, Careless Crappers Are Also Frivolous About Urination

69
Q

What is the precursor of mineralocorticoids, vitamin D, and bile acids?

A

Cholesterol!! Also the precursor of: glucocorticoids and androgens

70
Q

HMG-CoA reductase: pathway, step catalyzed, importance

A

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

71
Q

What enzyme is the target of statin drugs?

A

HMG-CoA reductase of cholesterol synthesis. Used to control hyperlipidemia

72
Q

Role of chylomicrons

A

Deliver triglycerides and cholesterol from INTESTINES –> BLOODSTREAM

73
Q

Role of VLDL

A

Delivers lipids made in liver via endogenous pathway to the tissues

74
Q

Role of IDL

A

Delivers lipids made in liver via endogenous pathway to the tissues

75
Q

Role of LDL

A

Delivers cholesterol to tissues. Known as “bad cholesterol”. Cholesterol uses LDL receptors

76
Q

Role of HDL

A

Delivers cholesterol to the liver from the tissues. Known as good cholesterol

77
Q

What happens to excess cholesterol?

A

Brought back to the liver to be converted into bile acid

78
Q

HMG-CoA synthase: pathway, step catalyzed, importance

A

Pathways: cholesterol, ketogenesis
Step catalyzed: eh
Importance: know that it is associated with cholesterol synthesis and is the rate limiting step of ketogenesis

79
Q

Carbamoyl phosphate synthetase II: pathway, step catalyzed, importance

A

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

Patient Presentation (9 decks)

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