Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FA13 Biochemistry > Biochem-03-Metabolism > Flashcards

Biochem-03-Metabolism Flashcards

1
Q

Cellular site of Acetyl-CoA production

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cellular site of TCA cycle

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Cellular site of Oxidative phosphorylation

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Cellular site of Fatty acid beta-oxidation

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cellular site of Glycolysis

A

Cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cellular site of Fatty acid synthesis

A

Cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cellular site of HMP Shunt

A

Cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Cellular site of Protein Synthesis

A

RER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Cellular site of Steroid Synthesis

A

SER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cellular site of Cholesterol Synthesis

A

Cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cellular site of Heme synthesis

A

Mitochondria and cytoplasm {HUGs take two}

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cellular site of Urea cycle

A

Mitochondria and cytoplasm {HUGs take two}

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cellular site of Gluconeogenesis

A

Mitochondria and cytoplasm {HUGs take two}

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Kinases

A

Use ATP to add a high-energy phosphate group to the substrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Phosphorylase

A

Adds inorganic phosphate onto substrate without using ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Phosphatase

A

Removes phsphate group from substrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Dehydrogenase

A

Catalyzes oxidation-reduction reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Carboxylase

A

Transfers CO2 groups with the help of biotin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Rate determining enzyme of Glycolysis

A
  • Phosphofructokinase-1 (PFK-1): Phosphorylaes Fructose-6P to make Fructose-1,6 bis-P
  • Positive regulators: AMP, Fructose-2,6
  • Negative regulators: ATP, citrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Rate determining enzyme of Gluconeogenesis

A
  • Fructose-1,6-bisphosphatase: dephosphorylates Fructose-1,6 bis-P to make Fructose-6P
  • Positive regulators: ATP
  • Negative regulators: AMP, Fructose-2,6-BP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Rate determining enzyme of TCA Cycle

A
  • Isocitrate dehydrogenase: decarboxylates Isocitrate to make alpha-ketoglutarate
  • Positive regulators: ADP
  • Negative regulators: ATP, NADH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Rate determining enzyme of Glycogen synthesis

A
  • Glycogen synthase: adds UDP-Glucose to glycogen chain
  • Positive regulators: Glucose, insulin
  • Negative regulators: epinephrine, glucagon
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Rate determining enzyme of Glycogenolysis

A
  • Glycogen phosphorylase: phosphorylates a glucose from glycogen and removes it as Glucose-1P
  • Positive regulators: AMP, epinephrine, glucagon
  • Negative regulators: Insulin, ATP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Rate determining enzyme of HMP shunt

A
  • Glucose-6-phosphate dehydrogenase (G6PD): oxidizes Glucose-6P to 6-Phosphogluconate
  • Positive regulators: NADP+
  • Negative regulators: NADPH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Rate determining enzyme of De novo pyrimidine synthesis

A
  • Carbamoyl phosphate synthetase II: transfers amine group from glutamine to CO2 (along with phosphate from ATP) to make carbamoyl phosphate
  • Positive regulators: ATP and PRPP
  • Negative regulators: UTP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Rate determining enzyme of De novo purine synthesis

A
  • Glutamine-PRPP amidotransferase: transfers amine group from glutamine to PRPP
  • Positive regulators: PRPP
  • Negative regulators: AMP, IMP, GMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Rate determining enzyme of Urea cycle

A
  • Carbamoyl phosphate synthetase I: Adds ammonium to bicarbonate to make carbamoyl phosphate
  • Positive regulators: N-acetylglutamate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Rate determining enzyme of Fatty acid synthesis

A
  • Acetyl-CoA carboxylase (ACC): carboxylates acetyl CoA to makes Molonyl CoA
  • Positive regulators: Insulin, citrate
  • Negative regulators: glucagon, palmitoyl-CoA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Rate determining enzyme of Fatty acid oxidation

A
  • Carnitine acyltransferase I: Transfers fatty acid to carnitine for transport across inner mitochondrial membrane
  • Negative regulators: Malonly-CoA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Rate determining enzyme of Ketogenesis

A
  • HMG-CoA synthase: Adds carbons of acetyl CoA to acetoacetyl CoA to make HMG CoA
  • Negative regulators: CoASH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Rate determining enzyme of Cholesterol synthesis

A
  • HMG-CoA reductase: reduces HMG-CoA to make Mevalonate
  • Positive regulators: Insulin, thyroxine
  • Negative regulators: glucagon, cholesterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

ATP production in aerobic metabolism per molecule of glucose

A
  • when using malate-aspartate shuttle for glycolysis NADH (heart and liver): 32 ATP
  • when using glycerol-3-phosphate shuttle for glycolysis NADH (muscle): 30 ATP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

ATP production in anaerobic glycolysis per molecule of glucose

A

2 net ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

ATP is an activated carrier of

A

Phosphoryl groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

NADH, NADPH, FADH2 are activated carriers of

A

Electrons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Coenzyme A, lipoamide are activated carriers of

A

Acyl groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Biotin is an activated carrier of

A

CO2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Tetrahydrofolates is an activated carrier of

A

1-carbon units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

SAM is an activated carrier of

A

CH3 groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

TPP is an activated carrier of

A

Aldehydes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Types of processes that generally use NAD+

A

Catabolic processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Types of processes that generally use NADPH

A
  • Anabolic processes (steroid, fatty acid synthesis)
  • respiratory burst
  • P-450
  • Glutathione reductase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Hexokinase vs. Glucokinase

A
  • Hexokinase is found in most tissues
  • Hexokinase has high affinity (low Km) and low capacity (low Vmax)
  • Hexokinase is uninduced by insulin and it is inhibited by glucose-6-phosphate (its product)
  • Glucokinase is found in the liver and beta cells of the pancrease
  • Glucokinase has low affinity (low Km) and high capacity (Vmax)
  • Glucokinase is induced by insulin and is not inhibited by glucose-6-phosphage
  • Glucokinase’s kinetic properties allow it to serve as a “sensor” of glucose availability in blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Overview of glycolysis

A
  1. Glucokinase/hexokinase phosphorylates Glucose to Glucose-6P
    • This requires ATP; reaction is irreversible
  2. Glucose 6-P gets isomerized to Fructose-6P
  3. Phosphfructokinase 1 (PFK1) phosphorylates Fructose-6P to Fructose-1,6 BP
    • This requires ATP; rate-limiting step; reaction is irreversible
  4. Fructose-1,6 BP gets split to Glyceraldehyde-3P and Dihydrooxyacetone-P
  5. Glyceraldehyde-3P gets phosphorylated to 1,3-Bisphosphoglycerate
    • this requires an inorganic phosphate; NAD+ becomes NADH
  6. A phosphate group is removed to make 3-Phosphoglycerate
    • this makes an ATP
  7. Isomerizations happen and Phosphoenolpyruvate is made
  8. Pyruvate kinase dephosphorylates Phosphoenolpyruvate to make Pyruvate
    • This makes ATP; reaction is irreversible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Regulation by Fructose-2,6 bis-P

A
  • Phosphofructokinase-2 phosphorylates Fructose-6P to Fructose-2,6 BP
  • Fructose bisphosphatase-2 dephosphorylates Fructose-2,6 BP to Fructose-6P
  • Fructose-2,6 BP is activator of PFK-1, this leads to increased glycolysis
  • Insulin decreases activity of FBPase-2 and increases activity of PFK-2; this leads to more glycolysis; this is mediated by a decrease in cAMP which leads to a decreased activity of protein Kinase A
  • Glucagon has the exact oposite effect of insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Pyruvate dehydrogenase complex

A
  • reaction: pyruvate + NAD+ + CoA -> Acetyl-CoA + CO2 + NADH
  • Requires the following cofactors {Tender Loving Care For Nancy}:
    • Thyamine pyrophosphate (B1)
    • Lipoic acid
    • Coenzyme A (B5)
    • FAD (B2)
    • NAD (B3)
  • Complex is similar to alpha-ketoglutarate dehydrogenase complex
  • Complex is activated by insulin, high ADP levels, high Ca+ levels, high NAD+/NADH ratio
  • Exercises leads to incrased NAD+/NADH ratio, increased ADP, increased calcium
  • Arsenic inhibits lipoic acid; leads to voiting, rice wter stools, garlic breath
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Complex inhibited by arsenic

A

Pyruvate dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Pyruvate dehydrogenase complex deficiency

A
  • Causes a backup of substrate (pyruvate and alanine) resulting in lactic acidosis
  • Most cases are due to mutations in X-linked gene for E1-alpha subunit of PDC
  • Findings: neurologic defects, usually starting in infancy
  • Treatment: increased intake of ketogenic nutrients (fat, increased lysine and leucine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Ketogenic amino acides

A

Lysine and Leucine {the onLy pureLy ketogenic aminoacids}

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Function of alanine aminotransferase

A
  • Alanine aminotransferase reversibly converts alanine to pyruvate, in the process transfering the amine group to alpha-kketoglutarate to make glutamate
  • requires B6 (pyridoxine)
  • Alanine is used as a shuttle to send nitrogen from muscles to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Function of pyruvate carboxylase

A
  • pyruvate carboxylase irreversibly adds CO2 to pyruvate to make oxaloacetate
  • requires B7 (biotin)
  • OAA used to replentish TCA cycle or for gluconeogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Function of Pyruvate dehydrogenase

A
  • removes CO2 from pyruvate, adds a CO2 and converts it to acetyl CoA to enter the TCA cycle
  • requires B1, B2, B3, B5, lipoic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Function of lactic dehydrogenase

A
  • Converts pyruvate to lactate (and converts NADH to NAD+)

* This is the end of anaerobic glycolysis and serves to replentish NAD+ pool

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Sites where there is a significant amount of anaerobic glycolysis in the body

A

RBCs, leukocytes, kidney medulla, lens, testes, cornea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Steps of TCA (Krebs) cycle

A

{Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate}
1. Citrate synthase adds the two carbons of Acetyl CoA to Oxaloacetate to make citrate
2. Citrate gets isomerized to Isocitrate
3. Isocitrate dehydrogenase decarboxylates isocitrate to make alpha-ketoglutarate
• This makes NADH and releases CO2
4. alpha-ketoglutarate dehydrogenase decarboxylates alpha-ketoglutarate to make Succinyl CoA
• has same requirements as pyruvate dehydrogenase (B1, B2, B3, B5, lipoic acid)
• This makes NADH and releases CO2
5. Succinyl CoA gets rid of CoA to make succinate
• GTP is made from GDP and inorganic phosphate
6. Succinate is oxydized to Fumarate
• FADH2 is made
7. Fumarate is hydrated to make Malate
8. Malate is oxydized to make oxaloacetate
• NADH is made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Net products of TCA cycle

A
  • 3 NADH, 1 FADH2, 2 CO, 1 GTP per acetyl-CoA

* 10 ATP per acetyl-CoA and 20 ATP per glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Steps of electron transport chain

A

1A. NADH passes on its electrons to Complex I, which uses some of this energy to pump protons to intermembrane space
1B. FADH2 passes on its electrons to Complex II (succinate dehydrogenase)
2. Complex I and Complex II pass on their electons to coenzyme Q
3. Conezume Q passes on the electrons to Complex III, which uses some of this energy to pump protons to intermembrane space
4. Complex III passes onelectrons to cytochrome C
5. Cytochrome C passes on the electrons to Complex IV
6. Complex IV passses on the electrons to Oxygen to make water; it also uses some of this energy to pump protons across the intermembrane space
7. Protons pass through Complex V (F0-F1/ATPase) and ATP is made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Rotenone

A

Inhibits elecron transport by inhibiting Complex I, causing a decreased proton gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Antimycin A

A

Inhibits electron transport by inhibiting Complex III, causing a decreased proton gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Cyanide

A

Inhibits electron transport by inhibiting Complex IV, causing a decreased proton gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

CO

A

Inhibits electron transport by inhibiting Complex IV, causing a decreased proton gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Oligomycin

A

Directly inhibits ATPsynthase (Complex V), causing an increased proton gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

2,4-Dinitrophenol (2,4-DNP)

A
  • Increases the permeability of the inner mitochondrial membrane, decreasing the proton gradient and increasing O2 consumption
  • ATP synthesis stops but electron transport continues and produces heat
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Aspirin overdose

A
  • Increases the permeability of the inner mitochondrial membrane, decreasing the proton gradient and increasing O2 consumption
  • ATP synthesis stops but electron transport continues and produces heat
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Thermogenin

A
  • Present in brown fat
  • Increases the permeability of the inner mitochondrial membrane, decreasing the proton gradient and increasing O2 consumption
  • ATP synthesis stops but electron transport continues and produces heat
66
Q

Steps of gluconeogenesis

A
  1. Pyruvate carboxylase carboxylates Pyruvate to Oxaloacetate in the mitochondria
    • This requires Biotin, ATP; activated by Acetyl-CoA
  2. OAA can’t cross mitochondria, so it goes through malate shuttle and then OAA is now in the cytoplasm
  3. PEP Carboxykinase decabroxylates OAA to pohosphoenolpyruvate
    • This requires GTP
  4. Through a few steps PEP gets converted to Glyceraldehyde 3-P
  5. Glyceraldehyde 3-P combines with DHAP to make Fructose 1,6 BP
  6. Fructose-1,6 Bisphosphatase dephosphorylates Fructose 1,6 BP to make Fructose 6-P
  7. Fructose 6-P isomerizes to Glucose 6-P
  8. Glucose-6-phosphatase dephosphorylates Glucose 6-P
    • This takes place in the ER
67
Q

Tissue sites that do gluconeogenesis

A
  • primairily in the liver
  • enzymes also found in kidney, intestinal epithelium
  • does not happen in muscle because it lacks glucose-6-phosphatase
  • deficiency of key enzyes causes hypoglycemia
68
Q

Fatty acides that can serve as glucose source

A
  • Odd chain fatty acids yield 1 propionyl-Coa during metabolism
  • Propionyl-CoA can enter the TCA cycle as succinyl-CoA to make OAA, then undergo gluconeogenesis
  • Even-chain fatty acids can’t make new glucose since they only yeild acetyl-CoA
69
Q

Purpose of HMP shunt (pentose phosphate pathway)

A
  • Provides a source of NADPH
  • Make ribose for nucleotide synthesis and glycolytic intermediates
  • occurs in the cytoplasm
  • Occrus in lactating mammary glands, liver, adrenal cortex (sites of fatty acid or steroid synthesis), RBCs
70
Q

Steps of HMP shunt

A
  1. glucose 6-P dehydrogenase (G6PD) takes Glucose-6P and makes Ribulose 5-P
    • This yields 2 NADPH and CO2; irreversible
  2. Phosphopentose isomerase can isomerize Ribulose-5-P to Ribose-5-P; This is reversible
  3. Transketolases can take two of Fructose-6-P, Glyceraldehyde-3-P, xylulose 5-P, Ribose-5-P and do 2-carbon exchanges to interconvert among them
    • Requires B1; reversible
71
Q

Respiratory burst

A

• Formation of reactive oxygen species:
1. NADPH oxidase makes superoxide anion from O2 and NADPH
2. Superoxide dismutase makes H2O2 from superoxide
3. Myeloperoxidase can tack on a Cl- to H2O2 and make hypochlorite (HOCl*)
• neutralization of oxygen species:
1. Glutathione peroxidase convertes H2O2 to water, and Reduced glutathione to oxidized glutathione
2. glutathione reductase replentishes reduced glutathione using NADPH
3. NADPH is replentished by G6PD in HMP shunt

72
Q

Chronic granulomatous disease

A
  • Deficiency in NADPH oxidase
  • WBCs can use H2O2 generated by invading organisms and converte it to ROIs
  • Catalase-positive species, however, neutralize their own H2O2, so these patients are more succeptible to them (S. aureus, Aspergillus, etc.)
73
Q

Glucose-6-phosphate dehydrogenase deficiency

A
  • X-linked disorder
  • most common human enzyme deficiency
  • Increased malarial resistance (because RBC’s have a more hostile ROI environment)
  • leads to decreased NADPH in RBCs, which leads to hemolytic anemia due to poor RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine, anti-TB drugs, infection)
  • Heinz bodies (oxidized hemoglobin precipitated in RBCs)
  • Bite cells: result from phagocytic removal of heinz bodies by splenic macrophages
74
Q

Steps of Fructose metabolism

A
  1. Fructokinase phoshporylates Fructose to Fructose-1-P
  2. Aldolase B splits Fructose-1-P I nto Dihydroxyacetone-P and Glyceraldehyde
    • Just as in glycolysis, DHAP can be isomerized to glyceraldehyde-3-P
    • This step bypasses the rate-limiting step of glycolysis (PFK-1)
  3. Triose kinase phosphorylates glyceraldehyde to glyceraldehyde-3-P which can go to glycolysis
    • Disorders in fructose metabolism cause milder symptoms athan analogous disorders of galactose metabolism
75
Q

Essential fructosuria

A
  • Autosomal recessive
  • Defect in fructokinase, leding to fructose apppearing in blood and urine
  • benign and asymptomatic, since glucose is not trapped in cells
76
Q

Fructoseintolerance

A
  • Autosomal recessive
  • Deficiency of aldolase B; Fructose-1-P accummulates, causing a decrease ina vailable phosphate (because it was phosphorylated); this inhibits glycogenolysis and glucogneogenesis
  • Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
  • treatment: decrease intake of fructose and sucrose (glucose + fructose)
77
Q

Steps of galactose metbolism

A
  1. Galactokinase phosphorylates galactose to galactose-1-P
  2. Uridyl transferase takes UDP-Glu and switches it with galactose, yielding Glucose-1-P and UDP-Gal; Glucose-1-P can then go on to glycolysis or gluconeogenesis
  3. 4-epimerase epimerizes UDP-Gal to UDP-Glu
78
Q

Aldose reductase reactions

A
  • Aldose reductase reduces Glucose to sorbitol, trapping it in the cell; this requires NADPH
    • Sorbitol dehydrogenase can then oxidize Sorbitol to fructose using NAD+
    • This pathway is important in seminal vesicles, as sperm use fructose for energy
  • Aldose reductase can also reduce galactose to galactitol
79
Q

Galactokinase deficiency

A
  • autosomal recessive
  • deficiency of galactokinase leads to galactitol accumulation if galactose is present in diet
  • relatively mild condition
  • Symptoms: galactose appears in blood and urine, infantile cataracts (can present as failure to track objects or to develop a social smile)
80
Q

Clasic galactosemia

A
  • Autosomal recessive
  • Absence of galactose-1-phosphate uridyltransferase leads to accumulation of substances including galactitol
  • Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
  • Treatment: exclude galactose and lactose (galactose + glucose) from diet
81
Q

Sorbitol

A
  • Glucose can be trapped in the cell by reducing it to its alcohol counterpart, sorbitol via aldose reductase
  • For sorbitol to be utilized again, it needs to be oxidized to fructose via sorbitol dehydrogenase
  • Tissues with an insufficent amount of sorbitol (schwann cells, retina, kidneys) dehdrogenase are at risk for sorbitol accumulation, which leads to osmotic damage: cataracts, retinopathy, peripheral neuropathy
  • High blood levels of galactose result in formation of galacittol via aldose reductase, which has similar effects
82
Q

Lactase deficiency

A
  • Lactase splits galactose into glucose and galactose
  • Age-dependent and/or hereditary lactose intolerance is due to the loss of lactase in the brush border
  • primairily affects african americans and asians
  • Leads to gastroenteritis: bloating, cramps, osmotic diarrhea
  • treatment: avoid dairy products or add lactase pills to diet
83
Q

Solely glucogenic amino acids

A
  • Essential:
    • Met
    • Val
    • His
  • Nonessential:
    • Gly
    • Ser
    • Arg
    • Cys
    • Pro
    • Ala
    • Glu
    • Gln
    • Asp
    • Asn
84
Q

Glucogenic/ketogenic amino acids

A
  • Essential:
    • Ile
    • Phe
    • Thr
    • Trp
  • Nonessential:
    • Tyr
85
Q

Solely ketogenic aminoacids

A
  • Essential:
    • Leu
    • Lys
86
Q

Acidic amino acids

A
  • Asp

* Glu

87
Q

Basic amino acids

A
  • Arg
  • Lys
  • His
88
Q

Steps of the urea cycle

A
  1. Carbamoyl phosphate synthetase I (CPS I) combines ammonium with bicarbonate to make carbamoyl phosphate
    • This is the rate-limiting step; it requires ATP; it occurs in the mitochondria
  2. Ornithine transcarbamoylase combines ornithine and carbamoyl phosphate to make citruline
  3. Citruline goes to the cytoplasm
  4. Argininosuccinate synthetase combines citruline with aspartate to make argininosuccinate
  5. Arginosuccinase splits argininosuccinate into arginine and fumarate
  6. Arginase splits Arginine into Urea and ornithine
  7. Ornithine goes into mitochondria
89
Q

Alanine transport of ammonium (alanine cycle)

A

• All aminotransferases require B6 to work
1. In the muscle, aminotransferases take an amine group from an amino acid (which becomes an alpha-ketoacid) and give it to alpha-ketoglutarate, which becomes glutamine
2. alanine aminotransferase (ALT) takes glutamine’s amine group (becoming alpha-ketoglutarate) and give it to pyruvate, which becomes alanine
3. Alanine travels to the liver
4. Alanine aminotransferase does the oposite reaction, yielding pyruvate and glutamate
5. Glutamate dehydrogenase takes ammonia out of glutamate (which becomes alpha-ketoglutarate)
6. the ammonia can then enter the urea cycle
• Aspartate aminotransferase can take the amine group from glutamate (which becomes alpha-ketoglutarate) and give it to oxaloacetate, which becomes aspartate and enters the urea cycle

90
Q

Cori cycle

A
  • Glucose in the liver becomes pyruvate and then lactate

* Lactate goes to liver and becomes pyruvate and then glucose

91
Q

Hyperammonemia

A
  • can be acquired (liver disease) orhereditary (enzyme deficiencies)
  • results in excess ammonium, which depletes alpha-ketoglutarate, leading to inhibition of TCA cycle
  • Ammonia intoxication: symptoms: tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
  • Treatment: limit protein in diet, benzoate and phenylbutyrate (bind amino acid and lead to excretion), lactulose (acidifies GI tract, trapping NH4 for excretion)
92
Q

Ornithine transcarbamoylase deficiency

A
  • X-linked recessive (ther urea cycle nzyme deficiencies are autosomal recessive)
  • Most common urea cycle disorder
  • Excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)
  • findings: increased orotic acid in blood and urine, decreased BUN, symptoms of hyper ammonemia
93
Q

Derivatives of Phenylalanine

A
  • Phenylalanine -> Tyrosine (requires BH4–tetrahydrobiopterin)
    • Tyrosine -> Thyroxine
  • Tyrosine -> Dopa (requires BH4)
    • Dopa -> Melanin
  • Dopa -> Dopamine (requires B6)
  • Dopamine -> NE (requires Vitamin C)
  • NE -> Epinephrine (requires SAM)
94
Q

Derivatives of Tryptophan

A
  • Tryptophan -> Niacin (requires B6)
  • Tryptophan -> Serotonin (requires BH4)
    • Serotonin -> Melatonin
95
Q

Derivatives of Histidine

A

Histidine -> Histamine (requires B6)

96
Q

Derivatives of Glycine

A
  • Glycine -> Porphyrin (requires B6)

* Porphyrin -> Heme

97
Q

Derivatives of Arginine

A
  • Arginine -> Creatine
  • Arginine -> Urea
  • Arginine -> Nitric oxide
98
Q

Derivatives of Glutamate

A
  • Glutamate -> GABA (requires B6)

* Glutamate -> Glutathione

99
Q

Catecholamine synthesis and tyrosine catabolism

A
  1. Phenylalanine hydroxylase hydroxylases phenylalanine to make tyrosine
    • This requires BH4 -> BH2
    • BH4 is replentished bydihydropteridine reductase using NADPH
  2. Tyrosine hydroxylase hydroxylases tyrosine to make Dopa
    • This requires BH4
  3. Dopa decarboxylase decarboxylases dopa to make dopamine
    • This requires B6
  4. Dopamine beta-hydroxilase carboxylases dopamine to make norepinephrine
    • This requires vitamin C
  5. Phenylethanolamine N-methyltransferase methylates NE to make Epi
    • This requires SAM
100
Q

MAO (monoamine oxidase) and COMT (catechol-O-methyltransferase)

A
  • degrade catecholamines by acting sequentially
  • Dopamine -> HVA
  • Norepinephrine -> VMA
  • Epinephrine -> Metanephrine
101
Q

Phenylketonuria (PKU)

A
  • autosomal recessive; 1:10,000
  • Screened 2-3 days after birth (normal at birth because of maternal enzyme)
  • due to decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor (malignant phenylketonuria)
  • tyrosine becomes an essential amino acid
  • Leads to increased phenylketones in urine (phenylacetate, phenyllactate, phenylpyruvate)
  • Findings: mental retardation, growth retardation, sizures, fair skin, eczema, musty body odor
  • Treatment: decrease phenylalanine intake (contained in aspartame), and increased tyrosine in diet
102
Q

Maternal PKU

A
  • Lack of proper dietary therapy of mother with PKU

* Findings in infant: microcephaly, emntal retardation, growth retardation, congenital hearth defects

103
Q

Phenylalanine/Tyrosine metabolism

A
  1. Tyrosine gets metabolized to Homogentisic acid
  2. Homogentisate oxidase converts homogentisic acid to maleylacetoacetate
  3. Maleylacetoacetate can be metabolized to fumarate
104
Q

Lkaptonuria (ochronosis)

A
  • Autosomal recessive
  • deficiency of homogentisic acid oxidase
  • findings: dark connective tissue, brown pigmented sclera, urine turns black (on prolonged exposure to air), arthrlagias (homogentisic acid is toxic to cartilage)
105
Q

Albinism

A
  • Several possible causes:
    • deficiency in tyrosinase (which synthesizes melanin from tyrosine)
    • Defective tyrosine transporters
    • Lack of migration of neural crest cells
  • lack of melanin results in an increased risk of skin cancer
106
Q

Reactions and derivatives of homocysteine

A
  • Homocysteine mehtyltransferase transfers methyl from THF to homocysteine, which becomes Methionine
    • This requires B12
    • Methionine can become SAM
  • Cystathionien synthase combines Homocysteine and serine to make cystathionine
    • This requires B6
    • Cystathionine can be split into cysteine and alpha-ketobutyrate
107
Q

Homocystinuria

A
  • 3 forms, all autosomal recessive:
    • cystationine synthase deficiency - treatment: decreased methionine and increased cysteine in diet, as well as increased folate and B12 in diet
    • decreased affinity of cystathionine synthase for pyridoxal phosphate - treatment: increased B6 in diet
    • Homocysteine methyltransferase deficiency
  • all forms result in excess homocysteine, and cysteine then becomes essential
  • findings: increased homocysteine in urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), atherosclerosis
108
Q

Cystinuria

A
  • Autosomal recessive; 1:7000
  • Defect of renal tubular amino acid transporter for cysteine ,ornithine, lysine, and arginine in the PCT of kidney
  • excess of cystine in the urine can lead to precipitation of hexagonal cyrstals and renal staghorn calculi
  • treatment: good hydration and urinary alkalinization
  • Cystine is made of 2 cysteins connected by a disulfide bond
109
Q

Metabolism of branched aminoacides

A
  1. Valine, Isoleucine, Leucine are deaminated to their alpha-ketoacids
  2. Alpha-ketoacids are decarboxylated by alpha-ketoacid dehdrogenases (which require B1)
    • Valine will become propionyl CoA (glucogenic via succinyl CoA)
    • Isoleucine will become Propionyl CoA (glucogenic) and Acetyl CoA (ketogenic)
    • Leucine will become Acetyl CoA (ketogenic) and Acetoacetate (ketogenic)
110
Q

Maple syrup urine disease

A
  • autosomal recessive
  • blocked degradation of branched amino acids due to decreased alpha-ketoacid dehydrogenases
  • leads to increase of alpha-ketoacids in blood (especially Leu)
  • Findings: severe CAN defects, mental retardation, death, urine smell like maple syrup
  • {I Love Vermont maple syrup from maple trees (with branches)}
111
Q

Hartnup disease

A
  • Autosomal recessive
  • defective neutral amino acid trnasporter on renal and intestinal epithelial cells
  • Causes tryptophan excretion in urine and decreased absorption from the gut
  • Leads to pellagra
112
Q

Glycogen regulation by glucagon/epinephrine

A
  1. Glucagon and Epinephrine activate adenylyl cyclase
  2. More cAMP is made, which activates protein kinase A
  3. Protein kinase A phosphorylates glycogen phorphosyrlase kinase to its active state
  4. Glycogen phosphorylase kinase phosphorylates glycogen phosphorylase, which makes it active
  5. Glycogen phosphorylase phosphorylates glycogen and leads to glycogenolysis
113
Q

Glycogen regulation by insulin

A
  1. Insulin leads to activation of protein phosphatase
  2. Protein phoshpatase dephosphorylates glycogen phosphorylase kinase (inactivating it)
  3. Protien phosphatase also dephoshphorylates glycogen phosphorylase (inactivating it)
114
Q

Bonds in glycogen

A
  • Branches have alpha (1,6) bonds

* Linkages have alpha (1,4) bonds

115
Q

Steps of glycogen synthesis

A
  1. Glucose-6-P is isomerized to Glucose-1-P
  2. UDP-glucose pyrophosphorylase adds a UDP to make UDP-glucose
  3. Glycogen synthase adds glucose to the existing glycogen chain and releases UDP
  4. Branching enzyme branches glycogen
116
Q

Steps of glycogenolysis

A
  1. Glycogen phosphorylase phosphorylates a glucose unit to make Glucose-1-P
  2. when a branch has 4 glucoses left, they are all removed by debranching enzyme
117
Q

Lysosomal metabolism of glycogen

A

Lysosomal alpha-1,4-glucosidase removes a glucose unit from glycogen

118
Q

Von Gierke’s disease (Type I glycogen storage disease)

A
  • Autosomal recessive
  • deficiency in glucose-6-phosphatase, leading to glycogen accumulation mainly in liver and kidney
  • Findings: severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly
119
Q

Pompe’s disease (Type II glycogen storage disease)

A
  • Autosomal recessive
  • deficiency in Lysosomal alpha-1,4-glucosidase (acid maltase), leading to accumulation of glycogen mainly in liver, heart, and skeletal muscle
  • Findings: Cardiomegaly and systemic findings leading to early death
  • {Pompe’s trashes the Pump (heart, liver, and muscle)}
120
Q

Cori’s disease (Type III glycogen storage disease)

A
  • Autosomal recessive
  • deficiency in debranching enzyme (alpha-1,6-glucosidase)
  • findings: milder form of type I with normal blood lactate levelse (gluconeogenesis is intact)
121
Q

McArdle’s disease (Type V glycogen storage disease)

A
  • autosomal recessive
  • deficiency in skeletal muscle glycogen phosphorylase, leading to accumulation of glycogen in skeletal muscle
  • Findings: increased glycogen in muscle, but cannot break it down, leading to painful muscle crmaps, myoglobinuria with strenuous exercise
  • {Mcardle’s = Muscle}
122
Q

Sphignolipid metabolism

A

• Purpose: making ceramide, which can then be reused
• Occurs in lysosomes
1. Hexosaminidase A: GM2 ganglioside -> GM3 ganglioside
2. GM3 ganglioside -> glucocerebroside
• alpha-galactosidase A: Ceramide trihexoside -> glucocerebroside
3. beta-glucocerebrosidase: Glucocerebroside -> Ceramide
1. Arylsulfatase A: sulfatides -> galactocerebroside
2. Galactocerebrosidase: Galactocerebroside -> ceramide
1. Sphingomyelinase: Sphingomyelin -> Ceramide

123
Q

Fabry’s disease

A
  • X-linked recessive sphingolipidosis
  • Deficiency in alpha-galactosidase A, which leads to accumulation of ceramide trihexoside
  • Findings: Peripheral neuropathy ofhands/fet, angiokeratomas, cardiovascular/renal disease
124
Q

Gaucher’s disease

A
  • Autosomal recessive sphingolipidosis
  • Most common lysosomal storage disease
  • Deficiency in glucocerebrosidase, which leads to accumulation of glucocerebroside, primairily in mononuclear phagocyte cells
  • Findings: Hepatosplenomegaly, aspectic necrosis of femur, bone crisis, gaucher’s cells (macrophages that looks like crumpled tissue paper)
125
Q

Niemann-Pick disease

A
  • Autosomal recessive sphingolipidosis
  • Deficiency in sphingomyelinase which leads to accumulation of sphingomyelin, primairily in phagocytes
  • Findings: Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cell
126
Q

Tay-Sachs disease

A
  • Autosomal recessive sphingolipidosis
  • Deficiency in Hexosaminidase A which leads to accumulation of GM2 ganglioside, primairily in CNS
  • Findings: Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, no hepatosplenomegaly (vs. Niemann-pick)
127
Q

Krabbe’s disease

A
  • Autosomal recessive sphingolipidosis
  • Deficiency in Galactocerebrosidase which leads to accumulation of galactocerebroside
  • Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
128
Q

Metachromatic leukodystrophy

A
  • Autosomal recessive sphingolipidosis
  • Deficiency in arylsulfatase A which leads to accumulation of cerebroside sulfate
  • Findings: Central and peripheral demyelination with ataxia, dementia
129
Q

Hurler’s syndrome

A
  • Autosomal recessive mucopolysaccharidosis
  • Deficiency in alpha-L-iduronidase which leads to accumulation of Heparan sulfate, dermatan sulfate in heart, brain, liver, etc.
  • Findings: Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
130
Q

Hunter’s syndrome

A
  • X-linked recessive mucopolysaccharidosis
  • Deficiency in Iduronate sulfatase which leads to accumulation of Iduronate sulfatase
  • Findings: Mild Hurler’s + aggressive behavior, no corneal clouding
131
Q

Steps of fatty acid synthesis

A

• Occurs in cytoplasm
1. Citrate shuttle: Acetyl CoA joins with OAA to make citrate, which moves from the mitochondria to the cytoplasm
2. ATP citrate lyase splits Citrate back into Acetyl CoA and OAA
3. Acetyl CoA carboxylase carboxylates Acetyl CoA to Malonyl CoA
• requires biotin; rate-limiting step; induced by insulin
4. Fatty acid synthases takes in one Acetyl CoA and 7 malonyl CoA (sequentially) to make Palmitate (16:0)
• Induced by insulin

132
Q

Steps of fatty acid oxidation

A

• Occurs in mitochondria
1. Fatty acids enter from cytoplasm to inter-membrane space
2. Fatty acyl-CoA synthetase makes fatty acyl CoA
3. Carnitine acyltransferase I switches CoA with carnitine to make FA-carnitine
• rate-limiting step; inhibited by malonyl-CoA
4. FA-carnitine goes through carnitine transporter to enter the matrix
5. Carnitine acyltransferase-2 switches carnitine with CoA to make FA-CoA
6. Fatty acyl-CoA dehydrogenase (LCAD, MCAD) makes acetyl-CoA and FADH2, NADH
• fatty acids with odd-number of carbons will make a propionyl-CoA

133
Q

Ketone bodies

A
  • Ketone bodies: aceto acetate and beta-hydroxybutyrate
  • acetoacetyl CoA -> HMG CoA -> Acetoacetate + acetyl CoA
    • Acetoacetate -> beta-hydroxybutyrate
    • acetoacetate -> acetone + CO2
  • Made in the liver after fatty acid oxidation
  • In prolonged starvation and diabetic ketoacidosis, OAA is depleted for gluconeogenesies
  • In alcoholism, excess NADH shunts OAA to malate; this stalls the TCA cycle, shunting glucose and FFA to th eproduction of ketone bodies
  • Breath smells like acetone
  • Urine test does not detec tbeta-hydroxybutyrate
134
Q

Energy per 1g of nutrients (protein, carbohydrate, fat)

A
  • 1 g of protein = 4 kcal
  • 1g of carbohydrate = 4 kcal
  • 1g of fat = 9 kcal
135
Q

Response to the fed state

A
  • Glycolysis and aerobic respiration

* Insulin stimulates the storage of lipids, proteins, glycogen

136
Q

Response to fasting state

A
  • major: hepatic glycogenolysis
  • minor: hepatic gluconeogenesisi, adipose release of FFA
  • glucagon, adrenaline stimulate use of fule reserves
137
Q

Response to starvation days 1-3

A
  • Blood glucose leel maintained by:
  • Hepatic glycogenolysis
  • Adipose release of FFA
  • Muscle and liver switching from glucose to FFA
  • Hepatic gluconeogenesis from peripheral substrates (lactate, alanine, adipose tissue glycerol, propionyl CoA)
  • Glycogen reserves are depleted after day 1
  • RBCs can’t use ketones
138
Q

Response to starvation after day 3

A
  • Ketone bodies become the main source of energy for the brain and heart
  • after depletion of adipose fat, vital protein degradation accelerations, leading to organ failure and death
  • amount of adipose stores determines survival
139
Q

Cholesterol synthesis

A
  1. Acetoacetyl-Coa + Acetyl-CoA -> HMG-CoA
  2. HMG-CoA reductase: HMG-CoA -> Mevalonate
    • rate-limiting step; inhibited by statins
  3. Many more steps then lead to cholesterol
140
Q

Steps of lipid transport

A
  1. dietary fat uptakein into intestine, packaged into chylomicrons and sent to lymph, then it’s dumped into venous cyrculation
  2. LPL lipase serves to remove fatty acids from glycerol and then chylomicron remnants are what is left
  3. Liver uptakes chylomycron remnants, then repackages everything and secretes VLDL
  4. LPL lipase removes fatty acids from glycerol and then IDL is what is left
  5. IDL can be re-uptaken by liver
  6. CETP transfers cholesterols from HDL to IDL to make LDL
141
Q

Pancreatic lipase

A

Degradation of dietary TG in small intestine

142
Q

Lipoprotein lipase (LPL)

A

degradation of TG circulating in chylomicrons and VLDLs

143
Q

Hepatic TG lipase

A

Degradation of TG remaining in IDL

144
Q

Hormone-sensitive lipase

A

Degradation of TG stored in adiposites

145
Q

Lecithin-cholesterol acyltransferase (LCAT)

A

catalyzes esterification of cholesterol for uptake and better packing into HDL

146
Q

cholesterol ester transfer protein (CETP)

A

Mediates transfer of cholesterol esters to other lipoprotein particles (makes LDL out of IDL)

147
Q

Apolipoprotein E

A
  • Mediates remnante uptake

* present in all lipoproteins except LDL

148
Q

Apolipoprotein A-I

A
  • activates LCAT

* Present in HDL only

149
Q

Apolipoprotein C-II

A
  • Lipoprotein lipase cofactor

* Present in chylomicron, VLDL, HDL

150
Q

Apolipoprotein B-48

A
  • Mediates chylomicron secretion

* Present in chylomicron, chylomicron remnant

151
Q

Apolipoprotein B-100

A
  • Binds LDL receptor

* Present in VLDL, IDL, LDL

152
Q

Function of chylomicron

A
  • Secreted by intestinal epithelial cells
  • Deliver dietary TG to peripheral tissue
  • delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triacylclygerols
153
Q

Function of VLDL

A
  • Secreted by liver

* Delivers hepatic TGs to peripheral tissue

154
Q

Function of IDL

A
  • formed in the degradation of VLDL

* delivers triglycerides and cholesterol to liver

155
Q

Function of LDL

A
  • Delivers hepatic cholesterol to peripheral tissue
  • formed by hepatic lipase modification of IDL in the peripheral tissue
  • taken up by target cells via receptor-mediated endocytosis
156
Q

Function of HDL

A
  • Secreted from both liver and intestine
  • mediates reverse cholesterol transport from periphery to liver
  • acts as a repository of ApoC and ApoE (which are needed for chylomicron and VLDL metabolism)
157
Q

familial dyslipidemia type I - hyperchylomicronemia

A
  • Autosomal recessive
  • lipoprotein lipase deficiency or altered apolipprotein C-II
  • increased blood level of chylomicrons, TG, cholesterol
  • causes pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas
  • no incresed risk for atherosclerosis
158
Q

familial dyslipidemia type Iia - familial hypercholesterolemia

A
  • Autosomal recessive
  • absent or decreased LDL receptors
  • increased blood level of LDL, cholesterol
  • causes tendon (achilles) xanthomas, and corneal arcus
  • causes accelerated atherosclerosis
159
Q

familial dyslipidemia type IV - Hypertriglyceridemia

A
  • Autosomal dominant
  • hepatic overproduction of VLDL
  • causes pancreatitis
160
Q

Abetalipoproteinemia

A
  • autosomal recessive
  • mutation in microsomal triglyceride transfer protein (MTP) gene; leads to decrase in B-48 and B-100, which lead to decreased chylomicron and VLDL synthesis and secretion
  • intestinal piospy shows lipid accumulation within enterocytes due to inability to export absorbe dlipid as chylomicrons
  • findings: failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness
  • symptoms appear in the first few months of life

FA13 Biochemistry (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions