Gluconeogenesis, HMP Shunt Flashcards
(88 cards)
1
Q
Gluconeogenesis irreversible enzymes
A
- Pyruvate carboxylase
- Phosphoenoyruvate carboxykinase
- Fructose-1,6-bisphosphatase
- Glucose-6-phosphate
2
Q
Pyruvate carboxylase reaction and location
A
Pyruvate + CO2+ATP ā> oxaloacetate
Mitochondia
2
Q
Pyruvate carboxylase is activated by
A
Acetyl coa
3
Q
Pyruvate carboxylase requirement
A
Biotin
ATP
4
Q
Phosphoenolpyruvate carboxykinase requirements
A
GTP
5
Q
Phosphoenolpyruvate carboxykinase reaction and location
A
Oxaloacetate to phosphoenolpyruvate
cytosol
7
Q
Fructose -1,6- bisphosphatase reaction and location
A
Fructose -1,6-BPā>fructose-6-P
cytosol
8
Q
Fructose -1,6- bisphosphatase regulation
A
Citrate+
Fructose 2,6-BP-
AMP -
ATP +
8
Q
Glucose-6-phosphatase reaction
A
Glucose -6-Pā>glucose
9
Q
Glucose-6-phosphatase LOCATION / AND ORGAN
A
ENDOPLASMIC RETICULUM
PRIMARILY IN LIVER
10
Q
Gluconeogenesis serves
A
To maintain euglycemia during fasting
11
Q
Gluconeogenesis tissues
A
Liver(primary)
Kidney
Intestinal epithelium
12
Q
Deficiency of key gluconeogenic enzymes cause
A
Hypoglycemia
13
Q
Muscle - gluconeogenesis
A
no ā> lacks glucose -6 phosphatase
15
Q
fatty acids/gouconeogenesis
A
Even chain fatty acids ā> cannot produce new, since they yield only acetyl-CoA equivalents
Odd-chain fatty acids ā> yield one propionyl-CoA during metabolism, which can enter TCA (as succinyl-CoA), undergo gluconeogenesis
15
Q
Propionyl-CoA can enter TCA cycle as
A
Succinyl - CoA
16
Q
Odd-chain fatty acids/gluconeogenesis
A
They yield one propionyl-CoA during metabolism, which can enter TCA (as succinyl-CoA), undergo gluconeogenesis
17
Q
Source of NADPH
A
HMP shunt
18
Q
HMP
A
Pentose phosphate pathway
19
Q
HMP provides a source of
A
NADPH
20
Q
HMP provides a source of from abundantly available
A
Glucose-6-P
21
Q
HMP yields
A
- NADPH
- Ribose for nucleotide synthesis
- Glycolytic intermediates
22
Q
How many pathways for HMP shunt
A
2.
Oxidative and nonoxidative
23
Q
NADPH function
A
- Glutathione reductase
- Cytochrome P-450
- Respiratory burst
- Anabolic process (steroid and farry acids synthesis)
24
Location of of oxidative HMP shunt
Cytoplasm
25
Location of nonoxidative HMP shunt
Cytoplasm
26
ATP/HMP shunt
NO ATP IS USED OR PRODUCED IN HMP SHUNT
27
Is oxidative HMP shunt reversible or irreversible
Irreversible
28
Sites of HMP shunt (organs)
Sites of fatty acid or steroid synthesis (lactating mammary glands, liver, adrenal glands), RBCs
29
Is nonoxidative reaction reversible or irreversible
Reversible
30
HMP shunt rate determining enzyme
G6PD
31
G6PD regulators
NADP+
| NADPH-
32
Oxidative HMP shunt reaction
Glucose-6-P + 2NADP --> CO2 + 2NADPH + Ribulose-5-P (G6PD/irreversible)
33
G6PD deficiency cellular features
1. Heinz bodies
| 2. Bite cells
34
Most common enzyme deficiency / mode of inheritance / PURPOSE
G6PD / XR
| increases
35
Bite cells
Result from the phagocytic removal of Heinz bodies (RBCs) by splenic macrophages
36
Most common enzyme deficiency / mode of inheritance
G6PD / XR
| increases
37
Heinz bodies
Oxidized/denaturated Hemoglobin precipitated within RBCs
39
G6PD deficiency anemia - mechanism
Decreased NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents
40
Factors that precipitate hemolysis in G6PD deficiency
1. Drugs: sulfonamides, primaquine, antituberculosis
2. Fava beans
3. Infections (ROS generated via inflammatory response can diffuse into RBCs and cause oxidative damage
41
Fructose metabolism
Fructose + ATP --> Fructose-1-P + ADP (Fructokinase)
Fructose-1-P --> Dihydroxyacetone-P + Glyceraldehyde (Aldolase B):
- Dihydroxyacetone-P --> Glyceraldehyde-3-P --> glycolisis
- Glyceraldehyde + ATP --> Glyceraldehyde-3-P (Trise kinase) --> glycolisis
- Glyceraldehyde + NADH --> Glycerol
41
Fructokinase reaction
Fructose + ATP --> F1P+ ADP
42
Is Essential fructosuria a severe disease?
No. It is a benign symptomatic condition
43
Essential fructosuria - mechanism and mode of inheritance
Defect in fructokinase
| AR
44
Essential fructosuria pathophysiology
Defect in fructokinase (AR)
| Fructose is not trapped in cells --> fructose in blood and urine
45
Essential fructosuria findings
Fructose appears in blood and urine
46
Fructose intolerance mode of inheritance
AR
48
Disorder of fructose metabolism vs galactose metabolism according symptoms
Disorder of fructose metabolism cause milder symptoms
48
aldolase B reaction
Fructose-1-P to glyceraldehyde or dihydroxyacetone -P
49
Fructose intolerance - deficiency of
Hereditary deficiency of aldolase B
50
Fructose intolerance pathophysiology
Hereditary deficiency of aldolase B. Fructose-1-P accumulates causing decreased availability of phosphate --> inhibition of glycogenolysis and glyconeogenesis
51
Fructose intolerance inhibits
1. Glycogenolysis
| 2. Gluconeogenesis
53
Symptoms of fructose intolerance present following
CONSUMPTION of fruit, juice, honey
54
Fructose intolerance/urine
1. Urine dipstick - (test for glucose only)
| 2. Reducing sugar can be detected in the urine (nonspecific for inborn errors of carbohydrate metabolsim)
55
Fructose intolerance symptoms
1. Hypoglycemia
2. Jaundice
3. Cirrhosis
4. Vomiting
55
Sucrose sequence
Glucose and fructose
56
Fructose intolerance treatment
Reduce fructose and sucrose (glucose and fructose) intake
57
Glyceraldehyde to glyceraldehyde-3-P - reaction
Triose kinase + ATP
58
Galactokinase deficiency
Hereditary deficiency of galacktokimase
60
Galactose metabolism
Galactose -->
a. Galactiol (Aldose reductase)
b. Galactose-1-P (Galactokinase) --> Glucose-1-P (Uridiltransferalase, 4-epimerse reverse it) --> Glycolysis/glycogenesis
60
Galactokinase deficiency pathophysiology
Galactitol (reduction product of galactose) accumulates if galactose present in diet
61
Is Galactokinase deficiency a severe condition / mode of inheritance
No. It is a relatively mild condition
| AR
63
Galactokinase deficiency sympoms
1. Galactose in urine and blood
2. Infantile cataracts
3. May initially present as failure to track objects or to develop a social smile
63
Classic galactosemia mode of inheritance
AR
64
Classic galactosemia pathophysiology
Damaged is cause by accumulation of toxic substances (including galactitol, which accumulate in the lens of the eye)
65
Classic galactosemia
Absence of galactose-1-phosphate uridyltransferase
66
Classic galactosemia treatment
Exclude galactose and lactose (galactose and glucose) fro diet
67
Lactose sequence
Galactose and glucose
68
Classic galactosemia symptoms
1. Failure to thrive
2. Jaundice
3. Hepatomegaly
4. Infantile cataracts
5. Intellectual disability
6. E. Coli sepsis in neonates
7. Pi depletion (in most serious defect)
69
Galactose/glycolisis/glycogenesis
Galactose-->galactose-1-P(galactokinase) --> glucose-1-P (uridyltransferase) --> glycolysis/glyconeogenesis
71
Lactase deficiency? types?
Insufficient lactase enzyme--> dietary lactose intolerance
| types: 1ry, 2ry, congenital
72
Lactase function
It is on the brush border and digests lactose (human and cow milk) into glucose and galactose
72
Secondary lactose deficiency
Loss of brush border due to gastroenteritis (rotavirus), autoimmune etc
73
Primary lactose deficiency
Age dependent decline after childhood (absence of lactase-persistent allele, common in people of Asia, Africa, native american descent
74
lactose deficiency symptoms
Bloating, cramps, flatulence, osmotic diarrhea
75
Congenital lactose deficiency
Rare, due to defective gene
76
Lactase deficiency treatment
Avoid dairy products
Add lactase pills to diet
Lactose free milk
77
Glucose alcohol counterpart
Sorbitol
78
Lactase intolerance lab findings
Stool-low ph
Breath- high hydrogen
Intestinal biopsy - normal with hereditary
79
Alternative method of trapping glucose in the cell
Convert it to sorbitol (its alcohol counterpart)
80
Glucose to sorbitol reaction
Aldose reductase and NADPH
81
Sorbitol to fructose
Sorbitol dehydrogenase + NAD
83
Tissues with sorbitol dehydrogenase
Liver, ovaries, seminal vesicles
84
Tissues without sorbitol dehydrogenase
Scwann cells, retina, kidneys has only aldose reductase
| Lens has primarily aldose reductase
84
G6PD deficiency is mom common in black or white
Black
85
Insufficient amount of sorbitol reductase consequences
Intracellular accumulation --> osmotic damage (cataracts, retinopathy, peripheral neuropathy) seen in chronic hyperglycemia in diabetes
87
G6PD deficiency evolutionary benefits
Malarial resistance
88
MCC of hemolyisis in G6PD anemia
infection
