Lecture 2 Flashcards

1
Q

Bioenergentics is affected by 3 factors? What are they and explain about each.

A

Enthalpy (H) - Total heat content
Entropy (S) - Disorder
Free energy (G) - Energy available to do chemical work and a measure of the spontaneity of chemical reactions

Temperature in Kelvin
K = C + 273

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2
Q

What is ΔG° and explain the conditions

A

Standard free energy at standard conditions
1 Molar
298 Kelvin
1 atm

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3
Q

What is the standard free energy of hydrolysis of ATP?

A

ΔG° is -7.3 kcal/mol for each of the 2 terminal phosphate groups

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4
Q

Locations of metabolic processes/pathways

A

Glycolysis - Cytosol of cell
Kreb cycle - matrix of mitochondria
ETC - Inner membrane of mitochondria

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5
Q

Process of ETC along with complexes

A

NADH donates electrons to Complex I which then transfers the hydrogen atoms to Coenzyme Q (Ubiquinone). Succinate dehydrogenase in Kreb cycle reduces succinate to form FADH2 which then transfers electrons to CoQ. CoQ is a mobile carrier than then accepts hydrogen atoms from complex I and II to transfer to complex III. Electrons pass from complex III to complex IV which then reduces O2 to water. The protons in the intermembrane space then get pumped out by ATP synthase (Complex V) to make ATP.

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6
Q

What does incomplete reduction of oxygen to water produce?

A

Reactive oxygen species such as superoxide and hydroxyl radical. These can be cleaned up with enzymes such as superoxide dismutase, catalase, and glutathione peroxidase.

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7
Q

What is the direction of electron flow in terms of standard reduction potential

A

From more negative E to higher/positive E.
More negative the E means more likely to give up electrons.

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8
Q

How much ATP does NADH and FADH2 generate?

A

NADH - 2.5 ATP 4 from I, 4 from III, 2 from IV = 10 H+ /4 = 2.5
FADH2 - 1.5 ATP 4 from III, 2 from IV = 6 H+ /4 = 1.5
4 H+ going through complex V produces 1 ATP

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9
Q

What do uncoupling proteins (UCPs) do to the ETC and what is produced as a result?

A

Uncoupling proteins increase the permeability of the inner mitochondrial membrane and these carrier proteins allow protons to re-enter the mitochondrial matrix to produce heat (Known as nonshivering thermogenesis)

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10
Q

Names of carbohydrates based on number of carbons
Also classification of carbohydrates.

A

3 Carbons: Trioses
4 Carbons: Tetroses
5 Carbons: Pentose
6 Carbons: Hexoses
7 Carbons: Heptoses
9 Carbons: Nonoses

Oligosaccharides - 3-10 monosaccharides
Polysaccharides - 10 monosaccharides

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11
Q

What are aldoses and ketoses?

A

Aldoses - Carbohydrates with aldehyde as their most oxidized functional group
Ketoses - Carbohydrates with keto as their most oxidized group

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12
Q

What are isomers, epimers, and enantiomers?

A

Isomers - Compounds that have the same chemical formula but different structures
Epimers - Carbohydrate isomers that differ in configuration around only 1 specific carbon atom
Enantiomers - Isomers that are mirror images of each other

Most sugars are D-sugars
Racemases are enzymes that can interconvert D and L isomers

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13
Q

What is the difference between pyranose and furanose?

A

Pyranose is a 6 membered ring while furanose is a 5 membered ring

Alpha is on the right and Beta is on the left in fisher projection
Alpha is on the bottom and Beta is on the top in haworth projection

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14
Q

Aldehyde group is a what agent and all monosaccharides are what sugar?

A

Aldehyde groups are reducing agents and all monosaccharides are reducing sugars

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15
Q

What is the importance of benedict’s reagent or Fehling’s soluition?

A

They can react with sugar to become reduced and colored and making the aldehyde group oxidized into a carboxyl group.

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16
Q

What do glycosyltransferases do?

A

They link sugars to form glycosidic bonds

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17
Q

Where does digestion of carbohydrates stop and why along with what enzyme is affected?

A

Digestion of carbs stops in the stomach due to the acidic environment in the stomach. This high acidity inactivates salivary a-amylase (key enzyme doing digestion). The contents reach the small intestine where the pancreas secretes bicarbonate to neutralize the acid and pancreatic a-amylase can continue starch digestion

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18
Q

What do glycosidases do?

A

Glycoside hydrolases hydrolyze glycosidic bonds to create monosaccharides (glucose, galactose, fructose)

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19
Q

What is the difference between amylose and amylopectin? What is the function of amylase?

A

Amylose is a straight chain of starch while amylopectin is a branch chain of starch. Amylase hydrolyzes random a(1->4) bonds

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20
Q

Where are GLUT-2 and GLUT-4 abundant and why is GLUT-4 insulin-dependent?

A

GLUT-2 is abundant in pancreatic B-cells, liver and kidney
GLUT-4 is abundant in adipose tissue and skeletal muscle and is insulin-dependent since GLUT-4 is found in the cytosol but moves into the membrane to work through insulin.

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21
Q

How does glucose, galactose, and fructose enter into enterocytes (Cell of the intestinal lining)?

A

Glucose and galactose enter through Sodium dependent-glucose transporter (SGLT) while fructose enters through GLUT-5 in which they move through secondary active transport. The sodium-potassium pump causes the concentration gradient of Na to be higher on the outside which allows sodium to go down its concentration gradient into the cell and the monosaccharides are coupled along. All 3 then can enter the blood vessel through GLUT-2 transporter. This occurs in the epithelial cells of the intestine.

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22
Q

Why do any defects in a specific disaccharidase activity cause diarrhea

A

Defects cause the passage of undigested carbohydrates into the large intestine which then causes water to be drawn from the mucosa into the large intestine causing diarrhea, bacterial fermentation of the remaining carbohydrate plus large volumes of CO2 and H2 gas causing abdominal cramps and flatulence.

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23
Q

Why is the pentose phosphate pathway important?

A

It produces NADPH (Reducing agent in fatty acid synthesis) and Ribose (Required for nucleic acid biosynthesis)
This pathway occurs in cytosol

24
Q

What is the importance of phosphorylating glucose?

A

Phosphorylation of glucose traps it into the cell through enzyme hexokinase/glucokinase

25
Q

Where are glucokinase and hexokinase found?

A

Hexokinase I-III isozymes in most tissues.
Glucokinase is a form of Hexokinase IV that is found in the liver and pancreas since a large amount of glucose is in the liver and pancreas

Glucokinase has a higher Vmax and higher Km than than hexokinase I-III

26
Q

Major regulatory points in glycolysis

A
  1. Glucose -> G-6-P through hexokinase/glucokinase in which hexokinase is inhibited by G-6-P and glucokinase inhibited by F-6-P to prevent backward flow.
  2. Irreversible phosphorylation of F-6-P to fructose-1,6-bisphosphate is catalyzed by phosphofructokinase-1 (PFK-1) and this is the most important control point/rate limiting/committed step of glycolysis
  3. PEP is converted to pyruvate by pyruvate kinase and is an irreversible reaction of glycolysis
27
Q

What does aldolase do in glycolysis?

A

Aldolase converts the 6 carbon Fructose-1,6-bisphosphate into 3 carbon molecules (G-3-P and Dihydroxyacetone phosphate).
Only G-3-P continues onto glycolysis

28
Q

What is the function of enolase and what can it be inhibited by?

A

Dehydrates 2-phosphoglycerate to phosphoenolpyruvate (PEP)
Inhibited by fluoride

29
Q

What does glycolysis yield?

A

Glucose + 2 Pi + 2 ADP + 2 NAD+ =

2 pyruvate + 2 NADH + 2 ATP

30
Q

How does pyruvate convert to Acetyl-CoA?

A

Pyruvate dehydrogenase

31
Q

What are the 3 enzymes of PDH complex along with the coenzyme each needs?

A
  1. Pyruvate dehydrogenase (E1) - Requires Thiamine pyrophosphate (TPP)
  2. Dihydrolipoyl transacetylase (E2) - Requires lipoic acid and CoA which is why arsenic poisoning occurs due to inhibition of E2 since it requires lipoic acid as a coenzyme
  3. Dihydrolipoyl dehydrogenase (E3) - FAD and NAD+
32
Q

Steps in TCA cycle where NADH and FADH2 are produced

A

NADH:
1. Isocitrate -> a-ketoglutarate through Isocitrate dehydrogenase
2. a-ketoglutarate -> Succinyl-CoA through a-ketoglutarate dehydrogenase
3. Malate -> Oxaloacetate through malate dehydrogenase

FADH2:
1. Succinate -> Fumarate through succinate dehydrogenase (Complex II)

33
Q

What enzyme isomerizes citrate to isocitrate?

A

Aconitase

34
Q

What does isocitrate dehydrogenase do/produce and why is it important?

A

Isocitrate dehydrogenase catalyses the irreversible oxidative decarboxylation of isocitrate to form a-ketoglutarate in which 1 NADH, 1 CO2 is produced and this is one of the rate-limiting steps of the TCA cycle.

35
Q

Where does GDP get phosphorylated to GTP in the TCA cycle?

A

When succinyl CoA is cleaved to form succinate by the enzyme succinate thiokinase (succinyl CoA synthetase)

36
Q

3 Enzymes that regulate the TCA cycle

A
  1. Citrate synthase
  2. Isocitrate dehydrogenase
  3. a-ketoglutarate dehydrogenase complex
37
Q

Important Steps in Gluconeogenesis

A
  1. Pyruvate to Oxaloacetate by pyruvate carboxylase
  2. oxaloacetate to Phosphoenolpyruvate by phosphoenolpyruvate carboxykinase
  3. Fructose-1,6-Bisphosphate to fructose-6-phosphate through fructose-1,6-bisphosphatase
  4. Glucose-6-phosphate to glucose through glucose-6-phosphatase
38
Q

Why does phosphorylation of glycerol to glycerol-3-phosphate occur in the liver?

A

Liver contains glycerol kinase enzyme whereas adipocytes lack glycerol kinase

39
Q

Amino acids that form pyruvate and oxaloacetate

A

Pyruvate:
1. Alanine
2. Serine
3. Glycine
4. Cysteine
5. Threonine

Oxaloacetate:
1. Aspartate
2. Asparagine

40
Q

Location of enzymes responsible for synthesis of PEP from pyruvate

A

Pyruvate carboxylase is located in the mitochondria to convert pyruvate to oxaloacetate
PEP carboxykinase is located within the cytoplasm and converts oxaloacetate to PEP

41
Q

Where is Glucose-6-phosphatase found?

A

Found only in liver and kidney to catalyze the irreversible hydrolysis of G-6-P to form glucose and Pi

42
Q

When is insulin released vs glucagon?

A

Insulin is released in a fed/full state to take in glucose through the bloodstream and even store some as glycogen.
Glucagon is released in a hungry state to signal liver and muscle cells to convert glycogen into glucose for energy.
Epinephrine similar to glucagon in which it stimulates glycogenelysis and inhibits glycogenesis

43
Q

Why does the muscle not convert G-6-P into glucose like the liver does?

A

Muscle does not have glucose-6-phosphatase to convert G6P into glucose so G6P enters into glycolysis immediately

44
Q

What is glycogen composed of and what bonds. Also where does glycogen synthesis occur?

A

Glycogen is synthesized from molecules of a-D-glucose with the primary glycosidic bond being a(1->4) linkage and branching containing a(1->6) linkage occurring after 8-10 glucosyl residues. Glycogen is synthesized in the cytosol and requires energy from UTP.

45
Q

What does glycogen synthase require for synthesis?

A

A primer either through a fragment of glycogen or through a protein called glycogenin

46
Q

What enzyme is responsible for degradation of glycogen?

A

Glycogen phosphorylase cleaves the a(1->4) glycosidic bonds to produce glucose-1-phosphate

47
Q

Which enzyme removes the single remaining glucose reside attached in the a(1->6) linkage to release free glucose?

A

Amylo-a(1->6)-glucosidase

48
Q

What enzyme is responsible for the conversion of G-1-P to G-6-P and where is it located?

A

Phosphoglucomutase and located in the cytosol

49
Q

What is the ratio of glucose-1-p to glucose in glycogen degradation?

A

8 G-1-P : 1 Glucose

50
Q

Activated form of glycogen phosphorylase vs glycogen synthase

A

Activated form of glycogen phosphorylase is the phosphorylated form whereas activated form of glycogen synthase is the dephosphorylated form

51
Q

3 Disaccharides and what they are composed of

A

Sucrose - Glucose + Fructose
Lactose - Galactose + Glucose
Maltose - Glucose + Glucose

52
Q

What does Glucose-6-phosphate dehydrogenase do?

A

Enzyme responsible for turning Glucose-6-phosphate into 6-Phosphogluconolactone in the pentose phosphate pathway

53
Q

What are the functions of NADPH?

A
  1. Used in reductive biosynthesis (Fatty acids)
  2. Reduction of H2O2 (Forms reduced glutathione)
  3. Maintain hemoglobin in its reduced form and protects against hemolysis
54
Q

What are glycosaminoglycans composed of?

A

They are based on a repeating disaccharide unit and contain amino sugars and acidic sugars (Hence negatively charged)

55
Q

What is mucopolysaccharidosis?

A

Hereditary disorder in which GAG accumulate in tissues causing symptoms such as skeletal and extracellular matrix deformities and intellectual disability (Mainly affects brain)
-Results in deficiency of lysosomal hydrolases

56
Q

What are proteoglycans composed of?

A

They are constructed of protein and glycosaminoglycans.
(Protein backbone with disaccharide branch chains)

57
Q

What are glycoproteins and how are they different from proteoglycans?

A

Glycoproteins are proteins to which oligosaccharides are covalently attached.
They differ in that the length of the carbohydrate chain in glycoproteins is relatively short (2-10 sugar residues) whereas glycosaminoglycans of proteoglycans are much longer.

Deficiency of lysosomal hydrolases results in oligosaccharidosis which results in partially degraded structures in the lysosome.