Biochem FA - p85 - 94 Metabolism Flashcards
(86 cards)
1
Q
A
2
Q
In skeletal muscle, glycogen converted to?
A
Glycogen undergoes glycogenolysis–> glucose-1-phosphate –> glucose-6-phosphate
3
Q
First step of glycogenolysis
A
Glycogen phosphorylase liberates glucose-1-phosphate residues off branched glycogen until 4 glucose units remain on a branch.
4
Q
T or F Glycogen is only degraded in the cytosol
A
F - A small amount of glycogen is degraded in lysosomes by α-1,4-glucosidase (acid maltase).
5
Q
What happens once glycogen phosphorylase has done its job?
A
Then 4-α-d-glucanotransferase (debranching enzyme ) moves 3 of the 4 glucose units from the branch to the linkage. Then α-1,6-glucosidase (debranching enzyme ) cleaves off the last residue, liberating glucose.
6
Q
Name the types of Glycogen storage disease (I, II, III, and V) and what the enzyme deficiency is
A
Von Gierke - G6Pase
Pompe - acid maltase (Lysosomal acid α-1,4glucosidase with α-1,6-glucosidase activity)
Cori disease - Debranching enzyme (α-1,6-glucosidase)
McArdle - Skeletal muscle glycogen phosphorylase (Myophosphorylase)
7
Q
A
Treatment: frequent oral
glucose/cornstarch; avoidance
of fructose and galactose
Impaired gluconeogenesis and
glycogenolysis
8
Q
A
PomPe trashes the PumP (1st and 4th letter; heart, liver, and muscle)
9
Q
A
Gluconeogenesis is intact
10
Q
A
Blood glucose levels typically
unaffected
McArdle = Muscle
11
Q
Findings
A
Progressive neurodegeneration,
developmental delay, hyperreflexia,
hyperacusis, “cherry-red” spot on
macula A , lysosomes with onion
skin, no hepatosplenomegaly (vs
Niemann-Pick).
12
Q
deficient enzyme
A
heXosaminidase A
(“TAy-SaX)
13
Q
Accumulated Substrate
Inheritance
A
GM2 ganglioside
AR
14
Q
findings
A
Early: triad of episodic peripheral
neuropathy, angiokeratomas B ,
hypohidrosis.
Late: progressive renal failure,
cardiovascular disease.
15
Q
deficient enzyme
A
α-galactosidase A
16
Q
accumulated subtrate
inheritance
A
Ceramide
trihexoside
(globotriaosylceramide)
XR
17
Q
Metachromatic
leukodystrophy
findings
A
Central and peripheral demyelination
with ataxia, dementia.
18
Q
Metachromatic
leukodystrophy
deficient enzyme
A
Arylsulfatase A
19
Q
Metachromatic
leukodystrophy
accumulated substrate
inheritance
A
Cerebroside sulfate
AR
20
Q
Krabbe disease
findings
A
Peripheral neuropathy, destruction
of oligodendrocytes, developmental
delay, optic atrophy, globoid cells.
21
Q
Krabbe disease
deficient enzyme
A
Galactocerebrosidase
(galactosylceramidase)
22
Q
Krabbe disease
accumulated substrate
inheritance
A
Galactocerebroside, psychosine
AR
23
Q
Findings
A
Most common.
Hepatosplenomegaly, pancytopenia,
osteoporosis, avascular necrosis of
femur, bone crises, Gaucher cells C
(lipid-laden macrophages resembling
crumpled tissue paper).
24
Q
deficient enzyme
A
Glucocerebrosidase
(β-glucosidase); treat
with recombinant
glucocerebrosidase
25
accumulated substrate
inheritance
glucocerebroside
AR
26
findings
Progressive neurodegeneration,
hepatosplenomegaly, foam cells
(lipid-laden macrophages) D ,
“cherry-red” spot on macula A .
27
deficient enzyme
sphingomyelinase
```
No man picks (Niemann-Pick) his nose with
his sphinger (sphingomyelinase).
```
28
accumulated substrate
inheritance
sphingomyelin
AR
29
Hurler syndrome findings
Developmental delay, gargoylism,
airway obstruction, corneal clouding,
hepatosplenomegaly.
30
Hurler syndrome deficient enzyme
α-l-iduronidase
31
Hurler syndrome :
accumulated substrate
inheritance
Heparan sulfate,
dermatan sulfate
AR
32
Hunter syndrome findings
Mild Hurler + aggressive behavior, no
corneal clouding.
33
Hunter syndrome deficient enzyme
Iduronate-2-sulfatase
34
Hunter syndrome:
Accumulated substrate
inheritance
Heparan sulfate,
dermatan sulfate
XR
35
Fatty acid synthesis requires transport of \_\_\_\_\_\_\_
from __________ to \_\_\_\_\_\_. Predominantly
occurs in \_\_\_\_\_\_, _____ \_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_, and
\_\_\_\_\_\_ \_\_\_\_\_\_\_.
Fatty acid synthesis requires transport of citrate
from mitochondria to cytosol. Predominantly
occurs in liver, lactating mammary glands, and
adipose tissue.
“SYtrate” = SYnthesis.
36
Long-chain fatty acid (LCFA) degradation
requires \_\_\_\_\_\_\_-\_\_\_\_\_\_\_\_ transport into the
\_\_\_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_.
Long-chain fatty acid (LCFA) degradation
requires carnitine-dependent transport into the
mitochondrial matrix.
CARnitine = CARnage of fatty acids.
37
38
Systemic 1° carnitine deficiency—
\_\_\_\_\_\_\_ defect in transport of ______ into the
\_\_\_\_\_\_\_\_\_ --\> toxic accumulation. Causes
\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_, and ________ \_\_\_\_\_\_\_\_.
Systemic 1° carnitine deficiency—
inherited defect in transport of LCFAs into the
mitochondria toxic accumulation. Causes
weakness, hypotonia, and hypoketotic
hypoglycemia.
39
Medium-chain acyl-CoA dehydrogenase
deficiency—
\_\_\_ ability to break down \_\_\_\_\_
\_\_\_\_\_ into acetyl-CoA accumulation
of fatty acyl ______ in the blood with
\_\_\_\_\_\_\_ \_\_\_\_\_\_\_.
Medium-chain acyl-CoA dehydrogenase
deficiency—
dec ability to break down fatty
acids into acetyl-CoA accumulation
of fatty acyl carnitines in the blood with
hypoketotic hypoglycemia.
40
Medium-chain acyl-CoA dehydrogenase
deficiency—
Causes \_\_\_\_\_, \_\_\_\_\_, \_\_\_\_\_\_, \_\_\_\_\_\_, ______ \_\_\_\_\_\_, \_\_\_\_\_\_.
Can lead to ______ \_\_\_\_\_\_in infants or children.
Treat by avoiding \_\_\_\_\_\_.
Medium-chain acyl-CoA dehydrogenase
deficiency—
Causes vomiting, lethargy, seizures, coma, liver dysfunction, hyperammonemia.
Can lead to sudden death in infants or children.
Treat by avoiding fasting.
41
In the \_\_\_\_\_, fatty acids and amino acids
are metabolized to \_\_\_\_\_and
\_\_\_\_\_(to be used in muscle and brain).
In the liver, fatty acids and amino acids
are metabolized to acetoacetate and
β-hydroxybutyrate (to be used in muscle and brain).
42
In prolonged starvation and diabetic ketoacidosis, _____ is depleted for gluconeogenesis.
In alcoholism, excess _____ shunts oxaloacetate to _____ .
All of these processes lead to a buildup of _____ ,
which is shunted into ketone body synthesis.
In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis.
In alcoholism, excess NADH shunts oxaloacetate to malate.
All of these processes lead to a buildup of acetyl-CoA,
which is shunted into ketone body synthesis.
43
Ketone bodies: \_\_\_\_\_, \_\_\_\_\_, \_\_\_\_\_.
Breath smells like \_\_\_\_\_(fruity odor).
Urine test for ketones can detect \_\_\_\_\_, but not \_\_\_\_\_.
RBCs cannot utilize ketones; they strictly use
\_\_\_\_\_.
HMG-CoA _____ for ketone production.
HMG-CoA _____ for cholesterol synthesis.
Ketone bodies: acetone, acetoacetate, β-hydroxybutyrate.
Breath smells like acetone (fruity odor).
Urine test for ketones can detect acetoacetate, but not β-hydroxybutyrate.
RBCs cannot utilize ketones; they strictly use
glucose.
HMG-CoA lyase for ketone production.
HMG-CoA reductase for cholesterol synthesis.
44
45
Fasting and starvation
Priorities are to supply sufficient _____ to the _____ and _____ and to preserve _____ .
Fasting and starvation
Priorities are to supply sufficient glucose to the brain and RBCs and to preserve protein.
46
Fed state (after a meal)
\_\_\_\_\_ and _____ respiration.
\_\_\_\_\_ stimulates storage of _____ , _____ , and _____ .
Fed state (after a meal)
Glycolysis and aerobic respiration.
Insulin stimulates storage of lipids, proteins, and glycogen.
47
Fasting (between meals)
Hepatic _____ (major); hepatic _____ , adipose release of _____ (minor).
\_\_\_\_\_ and _____ stimulate use of fuel reserves.
Fasting (between meals)
Hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFA (minor).
Glucagon and epinephrine stimulate use of fuel reserves.
48
Starvation days 1–3
Blood glucose levels maintained by:
-\_\_\_\_\_ glycogenolysis
-Adipose release of \_\_\_\_\_
-\_\_\_\_\_ and _____ , which shift fuel use from
\_\_\_\_\_ to FFA
-Hepatic _____ from peripheral tissue _____ and _____ , and from adipose tissue _____ and \_\_\_\_\_-\_\_\_\_\_ (from odd-chain FFA—the only triacylglycerol components that contribute to gluconeogenesis)
Glycogen reserves depleted after day \_.
RBCs lack _____ and therefore cannot
use ketones.
Starvation days 1–3
Blood glucose levels maintained by:
-Hepatic glycogenolysis
-Adipose release of FFA
-Muscle and liver, which shift fuel use from
glucose to FFA
-Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-
CoA (from odd-chain FFA—the only triacylglycerol components that contribute to gluconeogenesis)
Glycogen reserves depleted after day 1.
RBCs lack mitochondria and therefore cannot
use ketones.
49
Starvation after day 3
\_\_\_\_\_ stores (\_\_\_\_\_ _____ become the main source of energy for the brain). After these are depleted, vital protein degradation accelerates, leading to organ failure and death.
Amount of excess stores determines survival time.
Starvation after day 3
```
Adipose stores (ketone bodies become the main source of energy for the brain). After these are depleted, vital protein degradation accelerates, leading to organ failure and death.
Amount of excess stores determines survival time.
```
50
51
Cholesteryl ester transfer protein fxn
Mediates transfer of cholesterol esters to other lipoprotein particles.
52
Hepatic lipase fxn
Degrades TGs remaining in IDL.
53
Hormone-sensitive lipase fxn
Degrades TGs stored in adipocytes.
54
Lecithin-cholesterol acyltransferase fxn
Catalyzes esterification of 2⁄3 of plasma cholesterol.
55
Lipoprotein lipase fxn
Degrades TGs in circulating chylomicrons.
56
Pancreatic lipase fxn
Degrades dietary TGs in small intestine.
57
PCSK9 fxn
Degrades LDL receptor --\> Inc serum LDL. Inhibition --\> Inc recycling of LDL receptor --\> decserum LDL.
Rx/ Alirocumab, evolocumab
58
Apo **E** fxn
Mediates r**E**mnant uptake
| (**E**verything **E**xcept LDL)
59
Apo **A**-I fxn
**A**ctivates LCAT
60
Apo **C**-II fxn
Lipoprotein lipase **C**ofactor that **C**atalyzes **C**leavage
61
Apo B-48 fxn
Mediates chylomicron secretion into lymphatics
Only on particles originating from the intestines
62
Apo B-100 fxn
Binds LDL receptor
On VLDL, IDL, LDL
Only on particles originating from the liver
63
If you have LCAT or A-1 def, then you have dec \_\_\_\_\_?
HDL
64
Lipoprotein functions
Lipoproteins are composed of varying proportions of _____ , _____ , and _____ . _____ and _____ carry the most cholesterol.
Cholesterol is needed to maintain _____ \_\_\_\_\_ integrity and synthesize _____ \_\_\_\_\_ , _____ , and _____ \_\_\_\_\_ .
Lipoprotein functions
Lipoproteins are composed of varying proportions of cholesterol, TGs, and phospholipids. LDL and HDL carry the most cholesterol.
Cholesterol is needed to maintain cell membrane integrity and synthesize bile acids, steroids, and vitamin D.
65
Chylomicron fxn
Delivers dietary TGs to peripheral tissues. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. Secreted by intestinal epithelial cells.
66
VLDL fxn
Delivers hepatic TGs to peripheral tissue. Secreted by liver.
67
IDL fxn
Delivers TGs and cholesterol to liver. Formed from degradation of VLDL.
68
LDL fxn
Delivers hepatic cholesterol to peripheral tissues. Formed by hepatic lipase modification of IDL in the liver and peripheral tissue. Taken up by target cells via receptor-mediated endocytosis. **L**DL is **L**ethal.
69
HDL fxn
Mediates reverse cholesterol transport from periphery to liver. Acts as a repository for apolipoproteins C and E (which are needed for chylomicron and VLDL metabolism). Secreted
from both liver and intestine. _Alcohol ^ synthesis_. **H**DL is **H**ealthy.
what the fuck it's real
https://www.ncbi.nlm.nih.gov/pubmed/11067787
cheers!
70
Abetalipoproteinemia
Inheritance, gene mutation, and what is absent + deficient
Autosomal recessive.
```
Mutation in (MTTP) gene that encodes microsomal transfer protein (MTP).
Chylomicrons, VLDL, LDL absent.
```
Deficiency in ApoB-48, ApoB-100.
71
Abetalipoproteinemia Sx
Affected infants present
with severe fat malabsorption, steatorrhea, failure to thrive. Later manifestations include retinitis
pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia,
acanthocytosis. Intestinal biopsy shows lipid-laden enterocytes.
72
Abetalipoproteinemia Tx
Treatment: restriction of long-chain fatty acids, large doses of oral vitamin E.
73
AR familial dyslipidemias
Type I - Hyperchylomicronemia
Type III - Dysbetalipoproteinemia
74
AD familial dyslipidemias
Type II - Familial Hypercholesterolemia
Type IV - Hypertriglyceridemia
75
Familial dyslipidemias Type I—Hyperchylomicronemia pathogenesis
Lipoprotein lipase or
apolipoprotein C-II
deficiency
76
Familial dyslipidemias Type I—Hyperchylomicronemia ^ blood level
Chylomicrons, TG,
cholesterol
77
Familial dyslipidemias Type I—Hyperchylomicronemia clinical presentation
Pancreatitis,
hepatosplenomegaly, and
eruptive/pruritic xanthomas
(no inc risk for atherosclerosis).
Creamy layer in supernatant.
78
Familial dyslipidemias Type II—Familial hypercholesterolemia
## Footnote
pathogenesis
Absent or defective
LDL receptors, or
defective ApoB-100
79
Familial dyslipidemias Type II—Familial hypercholesterolemia
^ blood level
IIa: LDL, cholesterol
IIb: LDL, cholesterol,
VLDL
80
Familial dyslipidemias Type II—Familial hypercholesterolemia
clinical presentation
Heterozygotes (1:500) have
cholesterol ≈ 300mg/dL;
homozygotes (very rare) have
cholesterol ≈ 700+ mg/dL.
Accelerated atherosclerosis (may
have MI before age 20), tendon
(Achilles) xanthomas, and
corneal arcus.
81
Familial dyslipidemias Type III—Dysbetalipoproteinemia
pathogenesis
Defective ApoE
82
Familial dyslipidemias Type III—Dysbetalipoproteinemia
^ blood level
Chylomicrons, VLDL
83
Familial dyslipidemias Type III—Dysbetalipoproteinemia
clinical presentation
Premature atherosclerosis,
tuberoeruptive and palmar
xanthomas.
84
Familial dyslipidemias Type IV—Hypertriglyceridemia
pathogenesis
Hepatic overproduction of VLDL
85
Familial dyslipidemias Type IV—Hypertriglyceridemia
^ blood level
VLDL, TG
86
Familial dyslipidemias Type IV—Hypertriglyceridemia
Clinical presentation
Hypertriglyceridemia (\> 1000 mg/dL) can cause acute
pancreatitis. Related to insulin resistance.
