Carb Met Flashcards
(91 cards)
1
Q
GLUT 1
A
Ubiquitous but high expression in RBCs and brain
High affinity
2
Q
GLUT 2
A
Main transporter in liver
Low affinity
3
Q
GLUT 3
A
Main transporter in neurons
- High affinity
4
Q
GLUT 4
A
Present in skeletal muscle, heart, adipose tissue
- Insulin dependent
5
Q
3 Phases of Glycolysis
A
Investment, Splitting,, Recoup/Payoff
6
Q
Step 1 of Glycolysis
A
Glucose to Glucose6Ph
Reg Step
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
8
Q
Rate Limiting Step of Glycolysis
A
F6P to F1,6BP
via PFK1
9
Q
Regulation of PFK1
A
+: AMP, Insulin, F2,6BP
-: Citrate, Glucagon, ATP
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)
11
Q
Which enzyme cleaves F1,6BP
A
Aldolase A
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)
13
Q
Which reactions do substrate level phosphorylation in Glycolysis
A
1,3BPG to 3PG
via phosphoglycerate kinase
PEP to Pyruvate via Pyruvate
Kinase
14
Q
Which enzyme creates pyruvate
A
PEP to Pyruvate via Pyruvate Kinase
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
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
17
Q
Which glycolysis product is a hub for other carb metabolisms?
A
Gluc 6 Phos
18
Q
What is a common etiology associated with ineffective glycolysis?
A
hemolytic anemias
mainly PK problems
19
Q
Type 1 Diabetes
A
severe insulin deficiency due to loss of pancreatic β cells (likely due to immune destruction).
20
Q
Type 2 Diabetes
A
insulin resistance that progresses to loss of β cell function
21
Q
clinical markers of hemolytic anemia
A
elevated lactate dehydrogenase, unconjugated bilirubin
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
23
Q
where does gluconeogenesis occur
A
liver kidney small intestine
24
Q
what does gluconeogenesis convert
A
pyruvate into glucose
25
precursors for gluconeogenesis
lactate, amino acids, glycerol
26
is gluconeogenesis a reversal of glycolysis?
NO
| it just bypasses the energy barriers of the 3 glycolysis reactions
27
pyruvate carboxylase
```
converts pyruvate to oxaloacetate in gluconeogenesis
CO2 and ATP dependent
activated by acetyl CoA and cortisol
Biotin cofactor
MITOCHONDRIAL ENZYME
```
28
phosphoenolpyruvate carboxykinase
OAA to PEP in gluconeogenesis
| release of CO2 and GDP produced
29
Fructose 1,6 Bisphosphatase
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
30
Glucose 6 Phosphatase
gluconeogenesis counterpart of glucokinase and hexokinase
31
Positive Regulators of Glycolysis
```
Insulin
AMP
Glucose
F2,6BP
F1,6BP
```
32
Negative Regulators of Glycolysis
Glucagon, ATP, Citrate, Gluc 6 Ph, Fruc 6 Ph, alanine
33
Positive Regulators of Gluconeogensis
Glucagon, citrate, cortisol, thyroxine, acetyl CoA
34
Negative Regulators of Gluconeogenesis
ADP, AMP, Fru 2-6BP
35
how does pyruvate come out of the mitochondria in gluconeogenesis
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
36
PEPCK
Concurrent decarboxylation and phosphorylation of oxaloacetate to PEP (GTP used)
Transcription activated by cortisol, glucagon, thyroxine
in Gluconeogenesis
37
Fructose 1,6-Bisphophatase
Breaks down Fructose 1,6-bisphosphate to Fructose 6-P
Rate-limiting step
Activated: cortisol and citrate
Inhibited: AMP and F2,6BP
38
Glucose 6-Phosphatase
Dephosphorylation to form glucose
Only in liver, kidneys, small intestine and pancreas
Located in ER lumen
Activated by cortisol
39
Cori Cycle
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
F1,6BP deficiency
Similar to Tarui disease in glycolysis
Presents in infancy or early childhood
Hypoglycemia, lactic acidosis, ketosis
Disorders of Gluconeogenesis
41
Von Gierke disease
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
SGLT1
sodium/glucose/galactose transporter,
| secondary active transport
43
GLUT 5
takes in fructose
44
Polyol Pathway
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
Fructose Metabolism
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
Excessive fructose consumption can lead to pathological conditions
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
Galactose Metabolism
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
classic galactosemia
(most common form) is an inherited deficiency in galactose 1-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
Deficiency in Galactokinase
leads to accumulation of galacitol (carb alch) which reacts similarly to sorbitol
50
cataracts
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
Does pentose phosphate pathway produce energy?
NO
52
What is the purpose of the pentose phosphate pathway?
```
produce the sugar (ribose) for DNA and RNA
produce NADPH (very important for fatty acid synthesis bc reductive biosynthesis)
```
53
where does the pentose phosphate cycle take place?
cytosol
54
what gets oxidized in the oxidation phase of PPP?
Glucose 6 P to 6 Phosphoglucolactone via G6PD
NADPH produced (reduced NADP+)
(-) reg by NADPH
rate limiting and catabolic irreversible step
55
G6PD deficiency
Presentation of hemolytic anemia when NADPH need is elevated (infection, oxidizing medications).
56
What does NADPH regenerate?
glutathione (G-SH), an important antioxidant, detoxifies H2O2 with glutathione reductase
57
What is the second oxidative reaction in PPP?
Formation of Ribulose 5P and generation of NADPH
6 Phosphoglucolactone to Ribulose 5P via 6-phosphoglucolactone dehydrogenase
58
PPP – Non-oxidative Phase
Aka regenerative phase
A series of reversible reactions
End products shunt to glycolysis, gluconeogenisis or nucleotide synthesis pathways
59
What happens if there is excess Rib 5 P
Excess R5P (may not needed for nucleotide biosynthesis) is converted into other sugars that can be used by the cell for metabolism
60
What are some uses of Rib 5 Phos
```
nucleotide synthesis
G3P
Fructo 6 P
(glycolysis)
can be rearranged and sent for amino acid synthesis
other metabolisms
```
61
when is there a high demand for Rib 5 P
rapidly dividing cells (nucleotide synthesis), oxidative phase favored to produce Ribulose 5P
Possible to obtain ribose 5P from reversible non-oxidative steps
62
High demand for NADPH
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
Structure of Glycogen
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
Glycogen Storage Granules
Glycogen stored in liver, muscle, and other tissues
Granules contain not only glycogen but also the enzymes needed for glycogen metabolism
65
Liver glycogen
regulates blood glucose levels
66
Muscle glycogen
provides reservoir of fuel (glucose) for physical activity
67
3 Steps of Glycogenesis
Trapping and Activation of Glucose
Elongation of a glycogen primer
Branching of glycogen chains
68
Step 1 Glycogenesis
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
Step 2 Glycogenesis
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
Step 3 Glycogenesis
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
Step 1 Glycogenolysis
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
Glycogenolysis in Liver
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
Glycogenolysis in Muscle
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
2 Important Reasons for Glycogenesis
to maintain blood sugar
to provide energy to muscle
separately regulated processes
75
Glycogen phosphorylase
the rate limiting step of degradation
76
Glycogen synthase
the rate limiting step of synthesis
77
Phosphorylation of Glycogen Synthase
dephospho form active
| phospho form inactive
78
Phosphorylation of Glycogen phosphorylase
dephospho form inactive
| phospho form active
79
Why is Glycogenolysis also favored during exercise
Cellular Calcium is high and AMP high
80
Mechanism of Regulation by Insulin
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
Type 2 Diabetes
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
Blood glucose criteria
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
Mechanism of Regulation by Glucagon
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
Glycogen Storage Diseases
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
GSD 0
Deficiency in glycogen synthase
86
GSD1a/Von Gierke disease
Deficiency in glucose 6-phosphatase
| Inefficient release of free glucose into the bloodstream by the liver following gluconeogenesis and glycogenolysis.
87
GSD II/Pompe Disease
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
GSD III/Cori Disease
Deficiency in α-1,6,-glucosidase (debranching enzyme).
89
GSD IV/Andersen Disease
Deficiency in glucosyl (4:6) transferase (branching enzyme)
90
GSD V/McArdle Disease
Deficiency in muscle glycogen phosphorylase
91
GSD VI/Hers Disease
Deficiency in liver glycogen phosphorylase
