Carb Met Flashcards

1
Q

GLUT 1

A

Ubiquitous but high expression in RBCs and brain

High affinity

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2
Q

GLUT 2

A

Main transporter in liver

Low affinity

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3
Q

GLUT 3

A

Main transporter in neurons

- High affinity

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4
Q

GLUT 4

A

Present in skeletal muscle, heart, adipose tissue

- Insulin dependent

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5
Q

3 Phases of Glycolysis

A

Investment, Splitting,, Recoup/Payoff

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6
Q

Step 1 of Glycolysis

A

Glucose to Glucose6Ph

Reg Step

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7
Q

Hexokinase vs Glucokinase

A

Hexokinase: found in all cells, high affinity for glucose, inhibited by Gluc 6 Phosphate
Glucokinase: found in hepatocytes and pancreatic B cells, low affinity for glucose and affinity increases based on “fed” state, not that negatively impacted by Gluc 6 Phosphate

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8
Q

Rate Limiting Step of Glycolysis

A

F6P to F1,6BP

via PFK1

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9
Q

Regulation of PFK1

A

+: AMP, Insulin, F2,6BP

-: Citrate, Glucagon, ATP

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10
Q

PFK2/FBPase Regulation

A

PFK2 is active in dephosph form (impacted by insulin signaling)
FBPase is active in phosph form (impacted by Glucagon signaling = phosphorylation cascade)

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11
Q

Which enzyme cleaves F1,6BP

A

Aldolase A

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12
Q

What reaction in Glycolysis produces 2NADH

A

G3P to 1,3BPG
which also is a phosphorylation but not with ATP hydrolysis
it is done by glyceraldehyde 3P dehydrogenase (GAPDH)

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13
Q

Which reactions do substrate level phosphorylation in Glycolysis

A

1,3BPG to 3PG
via phosphoglycerate kinase

PEP to Pyruvate via Pyruvate
Kinase

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14
Q

Which enzyme creates pyruvate

A

PEP to Pyruvate via Pyruvate Kinase

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15
Q

Tauri Disease

A

Def in PFK 1

Exercise-induced muscle cramps and weakness bc lactate buildup

Hemolytic anemia

High bilirubin and jaundice

Symptoms can be mild; true incidence may be higher due to lack of recognition and diagnosis

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16
Q

Regulation of Pyruvate Kinase

A

Activated by F1,6BP and insulin
Inhibited by ATP, alanine, and glucagon
High insulin: stimulates protein phosphatase, dephosphorylation of PK, activated form
High glucagon: cAMP activates PKA, phosphorylation of PK, inhibited form

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17
Q

Which glycolysis product is a hub for other carb metabolisms?

A

Gluc 6 Phos

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18
Q

What is a common etiology associated with ineffective glycolysis?

A

hemolytic anemias

mainly PK problems

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19
Q

Type 1 Diabetes

A

severe insulin deficiency due to loss of pancreatic β cells (likely due to immune destruction).

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20
Q

Type 2 Diabetes

A

insulin resistance that progresses to loss of β cell function

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21
Q

clinical markers of hemolytic anemia

A

elevated lactate dehydrogenase, unconjugated bilirubin

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22
Q

Fanconi-Bickel syndrome

A

Autosomal recessive disorder.
Caused by mutation in GLUT 2 transporter (located in liver, pancreatic β cell, enterocytes and renal tubular cells).
Unable to take up glucose, fructose and galactose

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23
Q

where does gluconeogenesis occur

A

liver kidney small intestine

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24
Q

what does gluconeogenesis convert

A

pyruvate into glucose

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25
Q

precursors for gluconeogenesis

A

lactate, amino acids, glycerol

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26
Q

is gluconeogenesis a reversal of glycolysis?

A

NO

it just bypasses the energy barriers of the 3 glycolysis reactions

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27
Q

pyruvate carboxylase

A
converts pyruvate to oxaloacetate in gluconeogenesis
CO2 and ATP dependent 
activated by acetyl CoA and cortisol 
Biotin cofactor
MITOCHONDRIAL ENZYME
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28
Q

phosphoenolpyruvate carboxykinase

A

OAA to PEP in gluconeogenesis

release of CO2 and GDP produced

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29
Q

Fructose 1,6 Bisphosphatase

A

counterpart for PFK1 in gluconeogenesis
when glucagon stimulates cell, it phosphorylates the enzyme complex and activates the phosphatase and inactivates the PFK1 = no F26BP made

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30
Q

Glucose 6 Phosphatase

A

gluconeogenesis counterpart of glucokinase and hexokinase

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31
Q

Positive Regulators of Glycolysis

A
Insulin 
AMP 
Glucose
F2,6BP
F1,6BP
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32
Q

Negative Regulators of Glycolysis

A

Glucagon, ATP, Citrate, Gluc 6 Ph, Fruc 6 Ph, alanine

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33
Q

Positive Regulators of Gluconeogensis

A

Glucagon, citrate, cortisol, thyroxine, acetyl CoA

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34
Q

Negative Regulators of Gluconeogenesis

A

ADP, AMP, Fru 2-6BP

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35
Q

how does pyruvate come out of the mitochondria in gluconeogenesis

A

pyruvate converted to OAA
OAA is not permeable through Mit Mem
OAA is reduced into malate via mito malate dehydrog
malate is transported to cyto via malate shuttle
malate reoxidized to OAA = NADH made in the process
via cytosolic malate dehydrog

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36
Q

PEPCK

A

Concurrent decarboxylation and phosphorylation of oxaloacetate to PEP (GTP used)
Transcription activated by cortisol, glucagon, thyroxine

in Gluconeogenesis

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37
Q

Fructose 1,6-Bisphophatase

A

Breaks down Fructose 1,6-bisphosphate to Fructose 6-P
Rate-limiting step
Activated: cortisol and citrate
Inhibited: AMP and F2,6BP

38
Q

Glucose 6-Phosphatase

A

Dephosphorylation to form glucose
Only in liver, kidneys, small intestine and pancreas
Located in ER lumen
Activated by cortisol

39
Q

Cori Cycle

A

Links lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in liver

Lactase transported from RBC/Muscle to Liver
Liver then converts to pyruvate via Gluconeogenesis
then transports pyruvate back to RBC/Muscle

Prevents lactate accumulation, regenerates glucose

40
Q

F1,6BP deficiency

A

Similar to Tarui disease in glycolysis
Presents in infancy or early childhood
Hypoglycemia, lactic acidosis, ketosis

Disorders of Gluconeogenesis

41
Q

Von Gierke disease

A

Deficiency in glucose 6-phosphatase
Occurrence of 1 in 100,000 live births
Inefficient release of free glucose into the bloodstream by the liver in gluconeogenesis and glycogenolysis.

Patients exhibit marked fasting hypoglycemia, lactic acidosis, hepatomegaly due to buildup of glycogen, hyperlipidemia and potentially retarded growth.
Mutations in catalytic site of enzyme results in GSD 1a (Von Gierke disease)
Diet management is mainstay of therapeutic approach

42
Q

SGLT1

A

sodium/glucose/galactose transporter,

secondary active transport

43
Q

GLUT 5

A

takes in fructose

44
Q

Polyol Pathway

A

Glucose to Fructose

glucose to sorbitol (carb alch) via aldose reductase

sorbitol to fructose via sorbitol dehydrogenase

lack of sorbitol dehydrogenase = sorbitol buildup = cataracts !

45
Q

Fructose Metabolism

A

faster than glucose metabolism bc doesnt need to have the three irreversible steps
fructose is used to make tracylglycerols too (FATS)

Fruct to Fruct 6 Ph to Glyceraldehyde to glycerol to Glycerol 3P then combined with 3 FA

G3P from glyceraldehyde can go into glycolysis too

46
Q

Excessive fructose consumption can lead to pathological conditions

A

problems with how fructose is processed in the liver

Actions of fructokinase and triose kinase bypass the most important regulatory step in glycolysis, the phosphofructokinase-catalyzed reaction.

Fructose-derived G3P and DHAP are processed by glycolysis to pyruvate and acetyl CoA in an unregulated fashion.

Excess acetyl CoA converted to fatty acids, which can be transported to adipose tissue to form triacylglycerols, resulting in obesity.

Liver also begins to accumulate fatty acids, resulting in fatty liver.

47
Q

Galactose Metabolism

A

Galactose to Galactose 1 Phos via galactokinase

Galactose-1-P reacts with UDP Glucose via GALT enzyme

=Glucose-1-P made

then Glucose-1-P converted to Glucose -6-P which is sent to glycolysis

48
Q

classic galactosemia

A

(most common form) is an inherited deficiency in galactose1-phosphate uridyl transferase (GALT) activity.
Afflicted infants fail to thrive.
Symptoms:
Vomiting/diarrhea after consuming milk
Enlargement of the liver and jaundice, sometimes progressing to cirrhosis.
Cataracts in eyes
Lethargy and retarded mental development.
Significant elevation of blood-galactose levels, and presence of galactose in urine.
Diagnostic criterion: Absence of the transferase in red blood cells.
Treatment: Remove galactose (and lactose) from diet.
Although elimination of galactose from diet prevents liver disease and cataract development, majority of patients still suffer from central nervous system malfunction, most commonly a delayed acquisition of language skills.

49
Q

Deficiency in Galactokinase

A

leads to accumulation of galacitol (carb alch) which reacts similarly to sorbitol

50
Q

cataracts

A

Cataract is the clouding of the normally clear lens of the eye. If the transferase is not active in the lens of the eye, the presence of aldose reductase causes the accumulating galactose to be reduced to galactitol.

51
Q

Does pentose phosphate pathway produce energy?

A

NO

52
Q

What is the purpose of the pentose phosphate pathway?

A
produce the sugar (ribose) for DNA and RNA
produce NADPH (very important for fatty acid synthesis bc reductive biosynthesis)
53
Q

where does the pentose phosphate cycle take place?

A

cytosol

54
Q

what gets oxidized in the oxidation phase of PPP?

A

Glucose 6 P to 6 Phosphoglucolactone via G6PD
NADPH produced (reduced NADP+)
(-) reg by NADPH
rate limiting and catabolic irreversible step

55
Q

G6PD deficiency

A

Presentation of hemolytic anemia when NADPH need is elevated (infection, oxidizing medications).

56
Q

What does NADPH regenerate?

A

glutathione (G-SH), an important antioxidant, detoxifies H2O2 with glutathione reductase

57
Q

What is the second oxidative reaction in PPP?

A

Formation of Ribulose 5P and generation of NADPH

6 Phosphoglucolactone to Ribulose 5P via 6-phosphoglucolactone dehydrogenase

58
Q

PPP – Non-oxidative Phase

A

Aka regenerative phase
A series of reversible reactions
End products shunt to glycolysis, gluconeogenisis or nucleotide synthesis pathways

59
Q

What happens if there is excess Rib 5 P

A

Excess R5P (may not needed for nucleotide biosynthesis) is converted into other sugars that can be used by the cell for metabolism

60
Q

What are some uses of Rib 5 Phos

A
nucleotide synthesis 
G3P 
Fructo 6 P
(glycolysis) 
can be rearranged and sent for amino acid synthesis
other metabolisms
61
Q

when is there a high demand for Rib 5 P

A

rapidly dividing cells (nucleotide synthesis), oxidative phase favored to produce Ribulose 5P
Possible to obtain ribose 5P from reversible non-oxidative steps

62
Q

High demand for NADPH

A

non-oxidative products channeled into gluconeogensis for re-entry into PPP

lactating mammary glands have a high NADPH need

Lung and liver tissue also exhibit high PPP activity
Very high PPP activity in phagocytic cells

Basically any process that requires DNA/RNA upregulation -need high PPP activity

63
Q

Structure of Glycogen

A

homopolymer of glucose molecules with branches

Glucose molecules within chain linked together via α-1,4 glycosidic bonds

Branch points formed via α-1,6 glycosidic bonds between glucose monomers of separate chains

Non-reducing ends each contain a terminal glucose with a free hydroxyl group at Carbon 4

Reducing end consists of glucose monomer connected to a protein called glycogenin

Glycogen is degraded and extended from non-reducing end

64
Q

Glycogen Storage Granules

A

Glycogen stored in liver, muscle, and other tissues

Granules contain not only glycogen but also the enzymes needed for glycogen metabolism

65
Q

Liver glycogen

A

regulates blood glucose levels

66
Q

Muscle glycogen

A

provides reservoir of fuel (glucose) for physical activity

67
Q

3 Steps of Glycogenesis

A

Trapping and Activation of Glucose

Elongation of a glycogen primer

Branching of glycogen chains

68
Q

Step 1 Glycogenesis

A

Trapping and Activation of Glucose

Glucokinase/hexokinase in cytosol of hepatocytes and muscle cells catalyze phosphorylation of glucose to glucose-6-phosphate

Phosphoglucomutase then reversibly isomerizes glucose-6-phosphate to glucose-1-phosphate

Uridine diphosphate(UDP)-glucose pyrophosphorylase then transfers the glucose-1-phosphate to uridine triphosphate (UTP) which generates UDP-glucose (active form of glucose)

69
Q

Step 2 Glycogenesis

A

Elongation of a glycogen primer

Preexisting glycogen polymer serves as primer to which glucose units are added

Glycogen synthase (rate limiting enzyme). Catalyzes transfer of glucose from UDP-glucose to non-reducing end of glycogen chain. Forms α-1,4 glycosidic bonds between glucose molecules

70
Q

Step 3 Glycogenesis

A

Branching of glycogen chains:

When glycogen chain reaches 11 residues, a fragment of the chain (about 7 residues long) is broken off at an α -1, 4 link and reattached elsewhere via α -1, 6 link by glucosyl (4:6) transferase

Branching increases solubility of glycogen and increases number of terminal non-reducing ends.

71
Q

Step 1 Glycogenolysis

A

Chain shortening (release of Glu-1-P)

Glycogen phosphorylase (GP) (rate limiting enzyme) catalyzes cleavage of glucose residues as a glucose-1-phosphate from non-reducing end of glycogen
GP uses pyridoxal phosphate (vitamin B6) as cofactor
Phosphorolysis continues till GP gets within 4 residues of α-1,6 linkage of a branch point
72
Q

Glycogenolysis in Liver

A

In liver Glu-1-P converted to Glu-6-P by an epimerase and then to Glu by glucose-6-phosphatase. Free glucose released into blood stream.

73
Q

Glycogenolysis in Muscle

A

Myocytes in skeletal and cardiac muscle lack glucose-6-phosphatase and hence cannot hydrolyze Glu-6-P. Use it to generate energy via glycolysis and TCA cycle

74
Q

2 Important Reasons for Glycogenesis

A

to maintain blood sugar
to provide energy to muscle
separately regulated processes

75
Q

Glycogen phosphorylase

A

the rate limiting step of degradation

76
Q

Glycogen synthase

A

the rate limiting step of synthesis

77
Q

Phosphorylation of Glycogen Synthase

A

dephospho form active

phospho form inactive

78
Q

Phosphorylation of Glycogen phosphorylase

A

dephospho form inactive

phospho form active

79
Q

Why is Glycogenolysis also favored during exercise

A

Cellular Calcium is high and AMP high

80
Q

Mechanism of Regulation by Insulin

A

Formation of the insulin receptor complex
Activation of PKB
Translocation of GLUT4 to membrane
PKB phosphorylates PP1 (activate) and GSK3 (inactivate)
Active PP1 dephosphorylates glycogen synthase (activate) and dephosphorylates glycogen phosphorylase (inactivate)

GLUT 4
Protein kinase B (PKB)
Protein phosphatase 1 (PP1)
Glycogen synthase kinase 3 (GSK3)

81
Q

Type 2 Diabetes

A

insulin resistance

Mutations in insulin receptor and/or downstream signaling proteins
Down-regulation in receptor levels
Triggered by elevated insulin
Endocytosis and degradation of the insulin receptor
Defective receptors not replaced by translation

82
Q

Blood glucose criteria

A

Normal: 70-100 mg/dL (fasting), ≤ 140 mg/dL (fed)
Prediabetic/at risk: 100-125 mg/dL (fasting), > 140 mg/dL (fed)
Diabetes mellitus: ≥ 126 mg/dL (fasting), ≥199 mg/dL (fed)

83
Q

Mechanism of Regulation by Glucagon

A

Binding of glucagon to its GPCR turns on G protein
Activates AC which forms cAMP
Activates PKA
PKA phosphorylates glycogen synthase (inactivates)
PKA phosphorylates PK (activate)
PKA phosphorylates an inhibitor which inactivates PP1
Active PK phosphorylates glycogen phosphorylase (activates)

Net:
glycogen breakdown (via inactivation of glycogen synthase and activation of glycogen phosphorylase)
84
Q

Glycogen Storage Diseases

A

Autosomal recessive
Disorders that effect breakdown:
lead to hepatomegaly
Lead to hypoglycemia (Inability to maintain blood sugar)
Disorders that affect synthesis:
patients dependent on glucose rather than glycogen

85
Q

GSD 0

A

Deficiency in glycogen synthase

86
Q

GSD1a/Von Gierke disease

A

Deficiency in glucose 6-phosphatase

Inefficient release of free glucose into the bloodstream by the liver following gluconeogenesis and glycogenolysis.

87
Q

GSD II/Pompe Disease

A

Deficiency in Acid Maltase aka acid α -glucosidase

Impairs lysosomal glycogenolysis resulting in accumulation of glycogen in lysosomes
Disrupts normal functioning of muscle and liver cells

88
Q

GSD III/Cori Disease

A

Deficiency in α-1,6,-glucosidase (debranching enzyme).

89
Q

GSD IV/Andersen Disease

A

Deficiency in glucosyl (4:6) transferase (branching enzyme)

90
Q

GSD V/McArdle Disease

A

Deficiency in muscle glycogen phosphorylase

91
Q

GSD VI/Hers Disease

A

Deficiency in liver glycogen phosphorylase