Sugar-advanced metabolism Flashcards
(367 cards)
1
Q
a sum of enzyme-catalyzed reactions by which a living cell perpetuates and
replicates itself
A
Metabolism
2
Q
Intermediary/Energy metabolism:
A SET OF REACTION concerned with..
A
- generation or storing energy and with
- using that energy for biosynthesis of small molecules.
3
Q
Metabolism is associated with maintenance of cellular ______ & blood _______ levels
A
ATP, glucose
4
Q
using energy
derived from
catabolic
pathways;
endergonic
process
A
Anabolic process biosynthesis pathway
5
Q
Oxidative breakdown
of complex larger
molecules that
results in energy
release captured by
formation of high
energy compounds
(ATP); exergonic
process
A
catabolic
6
Q
a metabolic pathway that can be both, catabolic and anabolic
A
Amphibolic
7
Q
sugars with names containing the suffix -ose.
A
Saccharides
8
Q
Monosaccharides are stereoisomers:
* All monosaccharides in humans are…
A
D-stereoisomers
9
Q
Most stable confirmation of saccharides are ring structures.
What are the ring structures?
A
Six member rings (pyranose) & five membered ring (furanose)
10
Q
OH- group at position 1 in saccharides can adapt in ____or ____ confirmation.
which is more stable?
A
α or β
The β confirmation is more stable in glucose but polysaccharides (starch) and glycogen have glucose linked in the α confirmation.***
11
Q
Which complex carbohydrates is nutritionally most important?
A
Disaccharides
-maltose(glucose+glucose)
-lactose(glucose+ galactose)
-sucrose( glucose+ fructose)
12
Q
Complex carbohydrate that contain 2 to 10 monosaccharide units
A
Oligosaccharides
13
Q
Complex carbohydrate that is greater than 10 monosaccharide units
A
Polysaccharides
-Cellulose
* Starch
* Glycogen
* Glucan: Polysaccharide of D-glucose monomers
14
Q
What are the other (minor) carbohydrates?
A
glycogen, alcohol, lactic acid, pectin & dextran
15
Q
Polysaccharide starch: source of ___% of monosaccharides
A
80
16
Q
When does amylase action begin? end?
A
Starts in the mouth, continues in stomach to hydrolyze starch into maltose and other small polymers of glucose.
ends in about an hour, gastric secretions inhibit activity.
after chyme enters duodenum, pancreatic amylase is added.
17
Q
Disaccharides & oligosaccharides need to be converted to ___________ before absorption.
A
monosaccharides
18
Q
Chyme enters jejunum and ileum where four enzymes are located in the brush border of cells
lining the intestine, which are… ?
A
lactase, sucrase, maltase, & α-dextrinase.
–Monosaccharides are immediately absorbed into the portal blood.
19
Q
What are the Glucose transporters used to get glucose across cell membranes?
A
GLUT-1, GLUT-2, GLUT-3, GLUT 4 & GLUT-5
20
Q
Glucose transporter that…
has low affinity (high Km) to glucose.
* Found in areas with high glucose concentrations.
* Involved in insulin-independent glucose in small intestines, renal tubules &
liver
A
GLUT-2
21
Q
Glucose transporter that…
has a high affinity (low Km) to glucose.
* Found in glucose-sensitive, insulin independent cells of the brain & RBC.
A
GLUT-1, GLUT-3 & GLUT-5
22
Q
Glucose transporter that…
has an intermediate affinity to glucose
* Found in insulin-dependent muscle & adipose cells.
A
GLUT-4
23
Q
storage form of glucose in muscle &liver
A
Glycogen (Polymeric glucose)
24
Q
major source of energy & primary form of nutrition
A
Monosaccharide
25
Monosaccharides can be transformed into what metabolites?
- Glucose to ribose
– Glucose to oxidized / reduced forms, such as mannitol, glucuronic acid
--> important constituents of complex polysaccharides
26
Other functions of carbohydrates?
» Long chains of hyaluronic acid and keratin sulfate makeup components of synovial
fluid and connective tissue
» Heparin
» Integral proteins
» Secreted proteins
27
Fructose is Primarily metabolized in...
liver, kidney, and small intestine
28
In the liver, fructose is converted to?
In other tissues?
-fructose-1-p by fructokinase
-Phosphorylated by hexokinase
29
What are three disorders of fructose metabolism?
-Essential fructosuria
-Hereditary fructose intolerance
-Hereditary fructose-1,6-bisphosphatase deficiency
30
this disorder of fructose metabolism won't effect glycolysis
Hereditary fructose-1,6-bisphosphatase deficiency
31
What is known as false diabetes mellitus?
Essential fructosuria
32
Disorder of fructose metabolism:
results from a deficiency of
fructokinase in the liver
Essential fructosuria
33
Disorder of fructose metabolism:
results from a
deficiency of fructose-1-p aldolase of liver, kidney cortex and small intestine
Hereditary fructose intolerance
34
What are the disorders of Galactose metabolism?
-Classic galactosemia
-Galactosemia due to loss of galactokinase (GALK)
-Epimerase deficiency (GALE)
35
Disorders of Galactose metabolism:
due to loss of uridylyltransferase
(GALT)
Classic galactosemia
36
Disorders of Galactose metabolism:
Galactosemia due to loss of galactokinase (GALK)
- Both are lactose intolerant, can lead to blindness and fatal liver damage
Galactosemia due to loss of galactokinase (GALK)
37
Disorders of Galactose metabolism:
– 2 forms,
1) benign, 1) similar to transferase deficiency
Epimerase deficiency (GALE)
38
the liver controls blood glucose concentrations, how?
-Via glycogen levels
* Converts intestinally absorbed galactose & fructose to glucose
* Produces glucose via gluconeogenesis (glucose-6-phosphatase activity)
39
Liver also responsible for producing important glucose metabolites, like?
-Ribose
-Oxidizes/reduces to form complex monosaccharides
40
What is the primary energy source used by the brain?
Sugar
41
Glucose can make up to ___ pyruvate and _____ Acetyl CoA.
2, 2
42
Building up to glucose is called?
And breaking down glucose is called?
gluconeogenesis (Using non-carb sources to make glucose)
glycolysis
43
which is limited? which is unlimited storage?
glycogen storage is limited!
-not all Acetyl CoA can be processed to the TCA cycle
fat storage is unlimited
44
what is the storage form of glucose?
Glycogen
45
How is ATP and ADP related?
ATP/AMP:ADP:P* ratio
46
What influences the metabolic rate?
ATP levels
47
What is a major difference in HDL and LDL?
HDL-moves cholesterol to liver to be cleared
LDL-moves cholesterol to peripheral circulation
48
What is the starting point of the TCA cycle?
What is it also important for?
oxaloacetate
gluconeogenesis
49
Where is NAD+ and NADH mainly found?
NAD+- mitochondria
NADH- cytosol
50
What is the difference between alpha and beta confirmations?
?
If carbon #1 and carbon #5 is linked by oxygen ---> alpha confirmation.
51
How can you distinguish D-glucose from L-glucose?
-Look at the second to last carbon
-OH group on the right side ---> D-glucose
-OH group on the left side ---> L-glucose
52
What is maltose made up of?
2 glucose
53
What is lactose made up of?
glucose and galactose
54
What is sucrose made up of?
glucose and fructose
55
Only ___________ form of sugar can enter the cells.
monosaccharide
56
a minor carbohydrate that can be used as a blood thinner. It is very large and can also be used for patients with low blood volume.
dextran
57
If the first carbon has the OH group on top it is alpha or beta confirmation?
Beta
58
Km =
1/2 Vmax
59
What are the two processes involving glycogen?
-Glycogenesis
-Glycogenolysis
60
What are the two processes involving glucose?
-Glycolysis
-Gluconeogenesis
*Hexose MonoPhosphate Shunt
61
___________ produces the storage form of glucose: high MW polysaccharide composed of glucose.
Glycogenesis
62
Glycogenesis:
linked with a _______ glycosidic bonds and branches with ________ glycosidic bonds (every 10 untis*)
α (1-->4)
α (1-->6)
63
Where does glycogenesis occur?
cytoplasm (liver and muscle)
64
What is step #1 of glycogenesis?
glucose-6-phosphate is catalyzed by phosphoglucomutase to glucose-1-phosphate
65
What is step #2 of glycogenesis?
glucose is activated with UTP which is catalyzed by UDP-glucose pyrophosporylase to UDP-glucose
66
What is step #3 of glycogenesis?
glycogen synthase adds UDP-glucose to growing glycogen molecule.
67
What can glycogen synthase (GS) be controlled by?
by phosphorylation or dephosphorylation
68
Glycogen synthase (GS) is regulated by?
cAMP-dependent PKA phosphorylation
-GS activity inhibited by PKA phosphorylation***
69
* Hormones that increase cAMP (___________& __________) activate PKA. [inhibit glycogen formation]
glucagon, epinephrine
70
****GS activity is ___________ if phosphate is removed.
increased
71
Branching enzyme attaches ___ to __glucose units to glycogen via α (1-->6) glycosidic bonds
5, 6
72
________________ phosphatase removes phosphate group & as cAMP concentrations decline, glycogen
formation is increased
Insulin-regulated
73
What is the major point of regulation for glycogen synthesis?
Branching enzyme***
74
The process involved in producing glucose from glycogen?
Glycogenolysis
75
Glycogenolysis:
What cleaves glycogen to glucose-1-phosphate
Glycogen phosphorylase
76
Glycogenolysis:
Glycogen phosphorylase activity is increased following phosphorylation by ___________ which activated by ______.
phosphorylase kinase
PKA
77
Glycogenolysis:
*What does hormones that increased cAMP (glucagon and epi) do to PKA?
activates PKA so that glucose-1-phosphate formation increases
78
Glycogenolysis:
______________ converts glucose-1-phosphate into glucose-6-
phosphate
Phosphoglucomutase
79
Glycogenolysis:
__________________ removes phosphate in glucose is free to diffuse from liver into the circulation
(liver) glucose-6-phosphatase
80
-This is an old metabolic pathway, fully functional under Anaerobic conditions
-Essential for cells unable to function aerobically (have no mitochondria)
Glycolysis
81
What cells rely on glycolysis?
****RBC & some cells in the eye (lenz and retina)
82
What cells/organism undergo glycolysis?
all types
83
Where does glycolysis take place?
Hoe much energy does it extract from glucose?
cytosol
less than 5%
84
What are the three enzymes needed for glycolysis? ****
(Steps 1,3, and 10) step 6 is the connecting point?
-Hexokinase
-phosphofructo-kinase-1
-pyruvate kinase
85
Is glycolysis reaction #1-phosphorylation reversible or irreversible?
irreversible
86
liver or brain?
Hexokinase-
glucokinase-
Hexokinase-body
glucokinase-liver?
87
Glycolysis Reaction #1:
Catalyzed by Glucokinase in the _____ or Hexokinase in ______.
liver, muscle/fat
88
Glycolysis Reaction #1:
– Traps glucose inside the cell – charge at physiological pH
– Conserves metabolic energy
– Phosphates interact with enzyme active sites and lower activation energy
-Mg used as a cofactor
cf. Phosphorylation:
89
Glucokinase (Liver) is highly specific for ________.
Glucose
90
Glucokinase has a ___ Km for glucoase (about ___mM)
high, 10
-Not saturated at physiological blood glucose concentration
(4-5mM)
91
Glucokinase is inhibited by __________, but NOT __________.
fructose-6-phosphate
glucose-6-phosphate
92
Glucokinase is induced by __________.
insulin
93
What is the specificity of hexokinase?
Low specificity – phosphates most relevant hexoses
(Glucose, Fructose, Mannonse)
94
hexokinase has a _____ Km (___mM): saturated at all plasma glucose
concentrations
low, 0.1 (increased affinity)
-x100 lower than glucokinase
95
Hexokinase is inhibited by..,
glucose-6-phosphate (fructose and others?)
96
What effect does insulin have on hexokinase?
little effect on expression
97
*** In RBCs, rates of glycolysis is regulated by _________.
ATP/AMP+ADP
-Increased ATP or not enough ADP, glycolysis will shutdown*
98
Regulation of Glycolysis:
1.
2.
3.
1. Hexokinase/Glucokinase
2. Phophofructokinase-1 (PFK-1)
3. Pyruvate Kinase
99
Regulation of Glycolysis, Phophofructokinase-1 (PFK-1):
activated by:
inhibited by:
activated by: AMP, F-2, 6-BP
inhibited by: ATP, citrate
100
Regulation of Glycolysis, Pyruvate Kinase:
activated by:
inhibited by:
activated by: F-1, 6BP
inhibited by: ATP, Acetyl CoA, Alanine
101
Glycolysis reaction #6:
1. Anaerobic conditions:
2. Aerobic conditions:
1. Anaerobic conditions: conversion of pyruvate to
lactate by lactate dehydrogenase
2. Aerobic conditions: by Shuttles which passes H+ to
the mitochondrion.
102
What are the two major shuttles under aerobic conditions?
-Glycerol phosphate shuttle
-Malate-Aspartate shuttle
103
What is the reverse pathway of glycolysis?
Gluconeogenesis
104
gluconeogenesis is a process that produces glucose-6-phosphate from what three things?
-AA
-FA
-glycerol and lactate
105
Gluconeogenesis:
Glucose is only formed in ______ and ______: Glucose-6-phosphatase
*** liver, kidney
106
What are the primary pursers for glucose synthesis?
– Glucose only formed in liver & kidney: Glucose-6-phosphatase
– Lactate goes pyruvate,
– Alanine goes to pyruvate,
– Glycerol goes to glyceraldehyde-3-phosphate
107
*** Hexose Monophosphate Shunt
Pentose Phosphate Pathway:
produces ______ in two-step pathway.
-Oxidative & non-oxidative steps
ribose
108
Why is ribose and NADPH needed from the pentose phosphate pathway?
*Ribose used to produce nucleotides and nucleic acid
*Pathway produces NADPH which is important reducing agent for biosynthetic process ex) FA & Cholesterol synthesis
109
“Alternative glucose oxidation pathway”
Hexose Monophosphate Shunt
Pentose Phosphate Pathway
110
Hexose Monophosphate Shunt
Pentose Phosphate Pathway:
Which tiesues?
1. Active in FA & steroid synthesis: adrenal gland, liver, adipose tissue &
mammary gland
2. RBCs: Maintain their membrane integrity.
3. Rapidly dividing cells: require DNA synthesis
(Length of survival depends on this pathway)
111
Pentose phosphate pathway can be divided into what two parts?
1) Oxidative and 2) non-oxidative "A kind of “recycle pathway”
112
What are the organs and glands involved in hormonal regulation of carbohydrates?
-Pancreas
* Insulin (hypoglycemic)
* glucagon
* somatostatin
– Adrenal gland
* Cortisol
* epinephrine
– Thyroid
* thyroxine
– Pituitary (anterior)
* Growth hormones
113
Insulin-dependent diabetes is which type ____
1
114
Where is insulin synthesized from?
islet of Langerhans β cells of pancreas as preproinsulin.
-packaged in beta granules
115
Insulin:
➢ Enzymatic cleavage of pre-proinsulin first forms proinsulin
✓ goes to....
insulin + C-peptide
116
INSULIN consists of an α & β chain connected by _____ bonds
s-s
117
Insulin released from β cells after what stimulations?
neural, dietary or hormonal stimulation (GIP, Somatostatin, Bombesin)
118
Glucose, amino acids increase _____________ peptide which increase insulin.
gastric inhibitory
119
What are the major target organs of insulin action?
* Liver which decreases proteolysis, lipolysis, gluconeogenesis, and
glycogenolysis
* Muscle which increase protein synthesis
* Fat which increases triglyceride synthesis
120
Glucagon is Synthesized in islet of Langerhans ___ cells of the pancreas
alpha
121
what increases glucagon release?
AA & exercise
122
Secretion of glucagon is potent & irreversibly regulated by...
[glucose]blood
123
Increased glucagon increases what?
-increased glycogenolysis: activates PKA & phosphorylase kinase
–increased gluconeogenesis,
– ketogenesis by inhibiting
storage of TG in liver
– Fat increases lipolysis
124
Synthesized in islets of Langerhans δ cells of pancreas
Somatostatin (GI paracrine)
125
what is the circulatory half-life of somatostatin (GI paracrine)?
short, about 2 min
126
What is somatostatin released with?
[glucose]blood, AA, FA & GI hormones
127
Somatostatin acts locally to __________ insulin and glucagon secretion.
decrease
-The effect is to increase for period of time which did nutrients are
assimilated into the bloodstream
128
Cortisol:
glucocorticoid is released from the adrenal ________.
The secretion is regulated by ______.
cortex
ACTH
129
Cortisol results in increased blood glucose due to....
-increased gluconeogenesis in the liver
–increased enzymes in GLUCONEOGENESIS pathway
– Mobilization of AA from extra hepatic tissue
130
Epinephrine released from ___________ after stimulation
of SYMPATHETIC NERVES
adrenal medulla
131
How does epinephrine result in increased blood glucose?
-decreased insulin secretion
-increased glucagon secretion
-increased glycogenolysis
-increased
gluconeogenesis
132
Thyroxine (T4) results in an overall ________ in protein synthesis. What else does it increase?
protein
-in glucose uptake
-in glycolysis
-gluconeogenesis
-rate of glucose absorption from intestinal tract
-Also results in increased
insulin but a secondary to
increasing
blood glucose
133
What is an important effect of thyroxine (T4)?
increased rate of glucose absorption from intestinal tract***
134
*** GH counteracts “in general” the effects of...
insulin on glucose & lipid
metabolism, but shares protein anabolic properties with insulin.
135
GH results in an overall increase in blood glucose as a result of....
-decreased utilization glucose for energy
- increased in glycogen deposition in cells
-decreased uptake of glucose by cells ---> increase blood glucose
136
What is the enzyme used for oxidative decarboxylation?
Pyruvate dehydrogenase complex
Lipoate, TPP, FAD
137
Is oxidative decarboxylation reversable?
no
138
Oxidative Decarboxylation:
Involves both, oxidation-reduction and decarboxylation.
What agent always participates?
✴ NAD+ & NADP+ or other oxidizing agent always participates.
139
Is Oxidative Decarboxylation endergonic or exergonic?
always exergonic ΔG< 0
140
_____________________ always participates in oxidative decarboxylation &
often in simple decarboxylations
Thiamine pyrophosphate
141
Oxidative Decarboxylation:
The overall reaction is ____________ : FA cannot be converted into carbohydrate
irreversible
142
What is the allosteric regulation of PDH?
– Inhibition by ATP, acetyl-CoA and NADH
– Activation by AMP, CoA and NAD+
143
What is the covalent regulation of PDH?
– Activation by dephosphorylation [PD phosphatase]
– Inhibition by phosphorylation of E1(pyruvate dehydrogenase)
(by PD Kinase activated by ATP)
144
REFREASH TCA CYCLE
!
145
What is the prime site of the TCA cycle?
oxaloacetate
146
What are the three enzymes that regulate the TCA cycle?
-Citrate synthase
-Isocitrate dehydrogenase
-α-Ketoglutarate dehydrogenase
147
Key sites of Regulation of TCA:
Citrate synthase is inhibited by...
ATP, citrate, NADH and succinyl-CoA
148
Key sites of Regulation of TCA:
Isocitrate Dehydrogenase is inhibited by...
ATP, alpha ketoglutarate, and NADH
149
Key sites of Regulation of TCA:
α– Ketoglutarate dehydrogenase is inhibited by...
ATP, GTP, succinyl-CoA and NADH
150
Can pyruvate ONLY get into the TCA cycle through
decarboxylation?
No. Anaplerotic pathways.
-pyruvate carboxylase ---> oxaloacetate (ATP-dependent carboxylation reaction)
-Malic enzyme -----> Malate (pro- and eukaryotes)
-oxaloacetate ---> PEP by PEP-CK, heart and skeletal muscle (phosphoenolpyruvate carboxykinase)
151
Oxaloacetate is very important for...
gluconeogenesis
152
Where does gluconeogenesis mainly take place?
liver, not muscle
153
Gluconeogenesis:
7 out of 10 reactions are the reverse of __________.
glycolysis
154
The highly exergonic nature of the glycolysis is due to what reactions?
HK/GK, PFK-1, and pyruvate kinase reactions.
Three reaction cannot be reversible
155
Gluconeogenesis must get around the three irreversible reactions by a new set of exergonic reactions that drive the process in the _________ direction.***
opposite
156
What are the gluconeogenesis substrates?
-Lactate (pyruvate) – Cori cycle
-Glucogenic AA (all, except leu & Lys)
-Glycerol (from the breakdown of TG)
-All TCA intermediates
157
Is acetyl-CoA a TCA intermediate?
NO
158
What AA do NOT give you intermediates that fit into the TCA cycle?
leu and Lys
159
How is lactate (pyruvate) continuously produced?
-RBC metabolism
-excising muscles
160
Where are the majority of the enzymes responsible for gluconeogenesis are found?
cytosol, although some precursors are generated in the mitochondria
161
Cori cycle summary
[ Liver ] 2 lactate ->2 pyruvate -->(6) glucose
------------>
[ Muscle ] glucose (2ATP) --> 2 pyruvate --> 2 lactate
back to liver (by blood)
Net consumption of 4 ATPs
162
The Cori cycle is very energy ___________.
inefficient
163
How is pyruvate converted to PEP?
first reaction...
A biotin-dependent carboxylation of pyruvate by pyruvate
carboxylase to yield oxaloacetate
primes the TCA cycle
164
How is pyruvate converted to PEP?
second reaction...
A decarboxylation by phosphorenolpyruvate carboxykinase
(PEPCK) to produce PEP
165
Conversion of OAA to PEP can occur through the action of cytosolic or mitochondrial PEP-CK
What is it for Ala?
What is it for Lac?
Alanine- cytosolic
Lactose-mitochondrial
166
Gluconeogenesis, which occurs in the cytosol, requires _______
NADH
NADH “must” be generated in the cytosol or imported from the mitochondria
167
How is NAD+ supplied for glycolysis?
168
What is important for regulating gluconeogenesis pathway?
-PEPCK
-fructose 1,6 bisphosphatase
???
169
PEP is converted to ______ by the glycolytic enzymes acting in reverse.
F-1,6-BP
170
The PFK-1 reaction is bypassed in by a simple hydrolytic reaction
catalyzed by ______________________.
Fructose 1,6 Bisphosphatase
***This step represents the "major site of regulation" of gluconeogenesis
171
The irreversible GK reaction is reversed by the action of ________________ (a simple hydrolysis).
➢ G-6-phosphatase is present in the liver & kidney.
* Glucose can thus leave the liver and enter the blood.
Glucose-6-phophatase
172
Gluconeogenesis:
***Carbon atoms for the synthesis of glucose are provided from ________ or _________.
This is why protein wasting is a prominent phenomenon during starvation
or Type 1 diabetes
What provides the necessary energy required by gluconeogenesis?
lactate, amino acids
*Lipid oxidation
173
What is the major regulation site of gluconeogenesis?
The major allosteric modulator of the activities?
PFK-1/Fructose-1,6 Bisphophatase couple
Fructose-2,6 bisphosphate
174
Phosphorylated PFK-2 (inhibited)- decreased levels of F-2,6 BP =
Inactivating PFK-1 & activating Fructose-1,6 Bisphosphatase
175
disease associated with increased production and metabolism of glucose
What are the types?
- Type I
– Type II
– Secondary
– Gestational
176
Type 1 diabetes accounts for ____% of all cases of diabetes and is usually diagnosed before the age of ____.
5-10, 20
177
Causes of type 1 diabetes?
inherited, autoimmune or infection
178
What are the complications of type 1 diabetes?
Retinopathy, Neuropathy, Nephropathy,
Angiopathy*
Hyperlipidemia, Ketoacidosis, increased susceptibility to infection & lactic acidosis
179
Clinical presentation of ketoacidosis patients?
low HCO3-, normal pCO2, high anion gap and [glucose]blood ---> Low pH
180
What is the difference in type 1 diabetic and starvation induced ketoacidosis?
presence of hyperglycemia in type I diabetics and hypoglycemia in starvation.
181
____________ causes type I diabetes to use FA as an alternative
Insulinopenia
FA mobilized ----> increases acetyl-CoA
Excess AcCoA!acetoacetyl CoA --> HMG CoA
182
Type II diabetes accounts for _______ % of all diagnosed cases of diabetics
90-95
2% of Americans
often obesity related but appears to have a hereditary component
183
Onset of type II diabetes is usually after ____ years of age.
40
184
Type II diabetes is characterized by hyperglycemia and “presence of _________”
insulin
185
Diabetic ketoacidosis primarily occurs in type....
I diabetics; however,
can occur in type II diabetics
186
Gestational diabetes occurs in ____ % of pregnancies.
What causes it?
2-5
inability to secrete insulin towards the 4x increase in demand
187
What is the risk of gestational diabetes?
How is it treated?
-Hyperglycemia increases the risk of spontaneous abortion & birth defects
-Treated with insulin or hypoglycemia agents
188
What is the primary structural change in a protein happening with high blood glucose?
Covalent bonding of carbohydrates to proteins produced in presence of excess carbohydrates
elevation of GHb
189
The elevation of GHb occurs about ___ wks after sustained
elevation in blood glucose, and last ____ months
3, 2-3
190
What is used to assess adherence to insulin treatment?
Percent of glycosylated Hb (HbA1c)
191
What conditions/diseases is testing of HbA1c not good for? why?
-cystic fibrosis
-gest. diabetes
-pt. with chronic liver or kidney disease
-sickle cell anemia
because RBC turnover is too fast
192
Normal HbA1c %?
below 5.7%*
193
Prediabetes HbA1c %?
5.7-6.4%*
194
Diabetes HbA1c %?
6.5% or above*
195
HbA1c:***
* Child:
* Good diabetic control:
* Fair diabetic control:
* Poor diabetic control:
* Child:1.8-4%
* Good diabetic control: 7%
* Fair diabetic control: 10%
* Poor diabetic control:
13-20%
196
What is normal Glucose level range?
70-110 mg/dL
197
Decreased blood glucose concentration can result in mild to severe coma, seizures and death.
* Occurs when blood glucose is less than ____ mg/dL
50
Cf. According to ADA, less than 70 mg/dl
198
What are causes of hypoglycemia?
- Excess insulin
– Liver disease
– Alcoholism
– Renal insufficiency
– Malignancy (beta cell tumor)
– Infection
– Pregnancy
– malnutrition
199
Treatment for hypoglycemia
IV glucose
200
NADH Ethanol Metabolism...
-alcohol dehydrogenase converts, in the cytosol, EtOH to acetaldehyde & produces
NADH
* Acetaldehyde enters mitochondria and is oxidized by acetaldehyde
DH to acetate and generates NADH
201
The capacity to metabolize EtOH is dependent upon the ability to shuttle ______ into mitochondria.
NADH
202
In NADH ethanol metabolism, increased NADH inhibits....
gluconeogenesis, FA oxidation, &
glycerophosphate DH***
203
Hepatic Ethanol Toxicity:
NADH increases pyruvate to lactate, thus inhibiting pyruvate conversion to
glucose
(Inhibiting gluconeogenesis)
204
How does hepatic ethanol toxicity lead to "fatty liver" and hyperlipidemia?
-Acetate converted to acetyl-CoA, can’t be oxidized in TCA so converted to fat
-Inhibited glycerophosphate DH leads to more glycerophophate which
is a backbone of TGs,
205
Hepatic Ethanol Toxicity:
_______________ forms adducts with proteins, nucleic acids, leading to acute toxic effects
* EtOH inserted into membranes altering action potentials and depressing CNS function.
Acetaldehyde
206
Heparin is a type of
Is a mix of sulfonated polysaccharides
207
Glucuronic acid
helps remove harmful substances from the body
Is ethier a oxidized or reduced form of glucose
208
Galactose to
----galactose kinase--> galactose 1 phosphate
- type two galactosemia
209
Galactose 1 phosphate
---uridylyltransferase with UDP-gal-glu-1-P---> glucose 1 phosphate
type one galactosemia
210
Glucose 1 phosphate to
---phosphoglucomutase--> glucose 6 phosphate
211
Glucose 6 phosphate-->
G-6-P--->F-6-P--->F-1,6-BP
212
Lactose goes to what and then what
Galactose then glucose 1 phosphate
213
Maltose goes to what and then what
Glucose and then glucose 6 phosphate
214
Mannose goes to what and then what
Mannose 6 phosphate and then fructose 6 phosphate
215
Sucrose goes to either what or what or what
Fructose—> fructose 6 P
Glucose—> Glucose 6 P
Fructose—> fructose 1 P—> Dihydroxyacetone or glyceraldehyde
216
Glycerol goes to what
A glycerol phosphate then Dihydroxyacetone-P
217
Fructose to F-6-P by
Hexokinase in other tissues
218
Glucose to
Glucose—> G-6-P—-> F-6-P—-> F-1,6 BF
219
Fructose in liver by Fructose kinase pathway
1.) Fructose—> Fructose 1 phosphate by Fructose Kinase and ATP is converted into ADP
2.) Fructose 1 Phosphate——> either Glyceraldehyde or DHAP by enzyme Fructose 1-P aldolase
3A.) Glyceraldehyde—-> Glyceraldehyde 3 phosphate by enzyme Triose kinase and ATP to ADP
3B.) DHAP—> Glyceraldehyde 3 phosphate with enzyme TIM
220
Glucose to G-6-P to
F-6-P—> F,1,6 BP
221
Glucose 1 phosphate—> UTP to PPi and enzyme UDP-glc pyrophosphorylase to UDP- glucose
1.) UTP to PPi and enzyme UDP-glc pyrophosphorylase to UDP- glucose
2.)
222
Ribose is a
Glucose metabolite
223
Glycogenesis
The formation of glycogen from sugar
224
Gluconeogenesis
The making of sugar from non carb sources
225
Glycogeneisis
Produces the storage form of glucose
High MW polysaccharide composed of glucose
226
Glycogen is linked
Linked with a (1–>4) glycosidic bond and branches with a (1—>6) glycosidic bond (every 10 units)
227
Mutase
Catalyses the movement of a functional group from one location to another
228
Kinase
Transfers of a phosphate group from a ATP molecular to another another molecule
229
Transferase
Catalyzes the transfer of a group from one molecule to another
230
Pyrophosphorylase
Catatalyses the nterconversion of glucocose 1 phosphate and Uridine triphosphate (UTP) to inorganic phosphate and UDP glucose
231
Glycogenin
Involves in the Convertion glucose to glycogen
232
Pyruvate to blank in aerobic conditions
Acetyl COA
233
Pyruvate to blank in anaerobic conditions
Lactate in RBC's
234
NAD+ and FAD+ are special what
Proton acceptors
235
Oxidative form
NAD+ and FAD+
236
Reduced form
NADH and FADH
237
what is added to make NAD+ into NADH
a hydride ion H* + and a -
238
what are kinases
Recall that kinases are enzymes that catalyze the transfer of the terminal phosphoryl group from ATP to an acceptor nucleophile.
239
Step one glycolysis
one phosphate group are attached to one molecule of glucose 6 phosphate, ATP is converted to ADP with the help of Mg2+ and G10=-16.7 kj/mol
240
Hexokinases and magnesium
* The acceptor in the case of hexokinase is a hexose, normally D-glucose
* hexokinase also catalyzes the phosphorylation of other common hexoses, such as D-fructose and D-mannose.
* Hexokinase, like many other kinases, requires Mg2+ for its activity, because the true substrate of the enzyme is not ATP4- but the MgATP2- complex. Mg2+ shields the negative charges of the phosphoryl groups in ATP, making the terminal phosphorus atom an easier target for nucleophilic attack by an –OH of glucose.
241
Where are hexokinases
* Hexokinase is present in all cells of all organisms. Hepatocytes also contain a form of hexokinase called hexokinase IV or glucokinase, which differs from other forms of hexokinase in kinetic and regulatory properties.
* Two enzymes that catalyze the same reaction but are encoded in different genes are called isozymes.
242
Preparatory phase of glycolysis step two
Glucose -6-phosphate is converted into fructose-6-phosphate with the help of Mg2+. G10=1.7 kj/mols; The reaction proceeds readily in either direction,as might be expected from the relatively small change in standard free energy
243
The enzyme phosphohexose isomerase
catalyzes the reversible isomerization of glucose 6-phosphate, an aldose, to fructose 6-phosphate, a ketose.
244
The PFK-1 enzyme
catalyzes the transfer of a phosphoryl group from ATP
245
PFK-is
is essentially irreversible under cellular conditions, and it is the first“committed” step in the glycolytic pathway; glucose6-phosphate and fructose 6-phosphate have other possible fates, but fructose 1,6-bisphosphate is targeted for glycolysis.
245
The PFK-1 reaction
is essentially irreversible under cellular conditions, and it is the first“committed” step in the glycolytic pathway; glucose6-phosphate and fructose 6-phosphate have other possible fates, but fructose 1,6-bisphosphate is targeted for glycolysis.
246
PFK is considered what
PFK-1 was considered the rate-limiting enzyme, because it was known to be closely regulated by fructose 2,6-bisphosphate and other allosteric effectors.
247
some bacteria and protists and perhaps all plants have
PFK catalyzes the phosphorylation of fructose-6-phosphate into fructose-1,6-biphosphate also using Mg2+ to convert a ATP into ADP G10=-14.2 Kj/mol
248
More one PFK-1
Phosphofructokinase-1 is a regulatory enzyme, one of the most complex known.
* It is the major point of regulation in glycolysis.
* The activity of PFK-1 is increased whenever:
* the cell’s ATP supply is depleted
* when the ATP breakdown products, ADP and AMP (particularly the latter), are in excess.
* The enzyme is inhibited whenever the cell has ample ATP and is well supplied by other fuels such as fatty acids.
248
The activity of PFK-1 is increased when
* the cell’s ATP supply is depleted
* when the ATP breakdown products, ADP and AMP (particularly the latter), are in excess.
248
The enzyme fructose 1,6 bisphosphate aldolase often called aldolase is
catalyzes a reversible aldol condensation
249
Fructose 1,6 bisphosphate is cleaved to yield
two different triose phosphates, glyceraldehyde3-phosphate, an aldose, and dihydroxyacetonephosphate, a ketose
250
Although the aldolase reaction has a strong positive standard free energy change
in the direction of fructose1,6-bisphosphate cleavage, at the lower concentrations of reactants present in cells, the actual free-energy change is small and the aldolase reaction is readily reversible
250
step 4 of glycolysis
Fructose 1,6-bisphosphate <--> dihydroxyacetone + glyceraldehyde 3-phosphate.
Uses an aldolase enzyme.
251
Only one of the two triose phosphates formed by aldolase, Glyceraldehyde-3-phasphate can
can be directly degraded in the subsequent steps of glycolysis.
252
The other product, DHP is rapidly and reversibly converted to
glyceraldehyde 3-phosphate by the fifth enzyme of the sequence, triose phosphate isomerase
252
Step 5
Dihydroxyacetonephosphate <--> glyceraldehyde 3-phosphate
Uses triose phosphate isomerase enzyme.
253
Step 5 characteristics
This reaction completes the preparatory phase of glycolysis. The hexose molecule has been phosphorylated at C-1 and C-6 and then cleaved to form two molecules of glyceraldehyde 3-phosphate.
254
The payoff phase
Remember that one molecule of glucose yields two molecules of glyceraldehyde 3-phosphate; both halves of the glucose molecule follow the same pathway in the second phase of glycolysis. The conversion of two molecules of glyceraldehyde 3-phosphate to two molecules of pyruvate is accompanied by the formation of four molecules of ATP from ADP
255
The first step of the payoff phase
glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, catalyzed by glyceraldehyde 3-phosphate dehydrogenase
256
The acceptor of hydrogen in the glyceraldehyde 3-phosphate dehydrogenase is
is NAD
257
Because cells maintain only limited amounts of NAD
glycolysis would soon come to a halt if the NADH formed in this step of glycolysis were not continuously oxidized
257
Step 6
Glyceraldehyde 3-Phosphate + Pi <--> 1,3-biphosphoglycerate.
Uses G3P dehydrogenase enzyme.
NAD+ <--> NADH
258
step 7
1,3-bisphosphoglycerate + ADP <--> 3-phosphoglycerate + ATP+ mg2+
Uses phosphoglycerate kinase enzyme.
258
The enzyme phosphoglycerate kinase
transfers the high-energy phosphoryl group from the carboxyl group of 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate
259
Steps 6 and 7 are
exothermic together
260
Step 8
3-phosphoglycerate <--> 2-phosphoglycerate
Uses phosphoglycerate mutase enzyme and Mg2+
261
262
2,3 BPG
s initially phosphorylated by phosphoryl transfer from 2,3-BPG, which is required in small quantities to initiate the catalytic cycle and is continuously regenerated by that cycle.
263
Step 9
2-phosphoglycerate <--> Phosphoenolpyruvate (PEP)
Uses enolase enzyme.
Dehydration reaction (loss of water).
263
264
Enolase promotes
reversible removal of a molecule of water from 2-phosphoglycerate to yield phosphoenolpyruvate (PEP)
265
Step 10
PEP + ADP --> Pyruvate + ATP
Uses pyruvate kinase enzyme + mg2+ and K+.
266
TCA cycle step one
Oxaloacetate( 4C) + Acetyle CoA( 2C) --> Citrate
267
Too much citrate can be used to make
Fatty acid steroid synthasis
268
Citrate to
Isocitrate by enzyme Aconitase
269
Isocitrate to
a-ketoglutarate by Isocitrate dehydrogenase
270
a-ketogluterate to
Succinyl CoA by a-ketoglutarate dehydrogenase
271
A-ketogluterate can be used
for AA synthesis
272
Succinate to
Fumarate by Succinul dehydrogenase
273
Malate to
Oxaloacetate by malate dehydrogenase
274
Oxaloacetate to
PEP by PEP carboxykinase
275
PEP to either
Glucose of AA
276
Phosphatase
Dephosphatase in liver and kidneys
277
More glycogen becomes
Fat
278
Long chain fatty acids to
--> FA spiral--> Acetyl CoA by B-oxidation
279
16FA -->
8 Acetyl coA
280
16FA -->
8 Acetyl coA
281
Insulin has a
Anabolic function Inhibits fat burning
282
Acetyl coA-->
lipogenesis--> FAs
283
Amminoacids-->
Nitrogen pools
284
Nitrogen pool-->
-Pyruvate
- Acetyl coA
- NH3--> Urea cycle
285
ATP/AMP:ADP: P ratio is decreased
FA metabolism is stimmulated
286
Vegans dont eat meat
receptor hit BV and then cholestral can be internalized
287
Cholesterol is a
Steroid hormone
288
Endogenous cholesterol synthesis pathway
your body can make Cholesterol
289
Pentose phosphate pathway will
Reduce Oxidative damage
290
Too much NADH and FADH then citrate will exit the mitochondria and make
FAT
291
Citrate is exergonic products or endergonic products -->
products are endergonic
292
Acetyl coA + oxaloacetate to citrate is
Catabolic and exergonic
293
A high NADH can
fight Oxidative damage
294
NADH=
Redox potential elevated
295
As we age
Increase in NAP+ and FAP2+
296
Alpha confirmation
OH on bottom
297
Beta confirmation
OH is on top
298
Km values indicate how strong
Interaction of molecules
299
Velocity vs what
Substrate
300
Vmax is
Maximum velocity of reactions
301
Km is
is Substrate concentration that is required to make speed to reach 1/2 vmax
302
lower kM=
high affinity
303
Higher kM
lower affinity
304
too much glucose in cells
apoptosis
305
glucose is important in
regulating osmo
306
Obligatory glycolysis
Lack of mitochondria= RBC
307
Glucuronic acid is important in
clearing bilirubin
308
Heparin is a
Anti-oxidant
309
there is no heparinized
Serum
310
Integral proteins
Glycolysalated proteins
311
Fructose 1-6 Bisphosphatase will influence what
Gluconeogenesis
312
GLycogen to
Glucose 1 phosphate
313
UDP gal for
UDP glucose
314
1- benign form of epimerase deficiency
only in RBC and WBC
315
transferace form of epimerase defciency
whole body
316
Glucose UDP to
glycogen-G-G-G glycogen synthase
317
Epipinephere
Sympathetic nervous system- HR increase- ATP increase-- ADP and AMP increase
318
Glycogen synthase activity is increased if blank is removed
Phosphate
319
PKA inhibits glycogen synthesis but enhances
Glycogenolysis
320
regulation of Pyruvate dehydrogenase
-Allosteric regulation
inhibited by ATP, acetyl coA, and NADH
Activated by AMP, CoA, and NAD+
- Covalent regulation
Activated by Dephosphorylation (PD phosphatase)
Inhibited by phosphorylation of E1(pyruvate dehydrogenase) ( by PD kinase activated by ATP)
321
Pyruvate with enzyme Pyruvate dehydrogenase -->
Acetyl coA with lose of CO2
322
Only small FA can
be used to go into the mitochondria and make acetyl coA
323
Pyruvate dehydrogenase complex cofactors
Lipoate, FAD+, and TPP
324
Pyruvate dehydrogenase complex
E1= real pyruvate dehydrogenase
E2= Dyhydrolipamide transferase
E3= Dihydrolipoamide dehydrogenase= is the dehydrogenase
325
Thiamine pyrophosphatase is needed in
Oxidative decarboxylation and simple decarboxylation
326
gluconeogenisis components
Glyceral, AA, and lactate
lactate= to pyruvate
alanine= to pyruvate
glyceral= to glyceraldehyde 3 phosphate
327
thrid name for Pentose phosphate pathway
Alternative glucose oxidation pathway
328
Glucose becomes ribose through
hydrolysis
329
Ribose is used in
Nucleotides and nucleic acids-utilization of pentose
330
PPP=NADPH=
used in FA and cholesterol synthesis
331
liver=
lipogenesis FA and cholestral synthesis
332
Mammary gland
FA storage
333
NAPDH can be a source of hydrogen for
Oxidized glutathione
334
Lenghts of survival of cells depend on
Pentose phos pathway
335
glucose can get into cells by
Glucose transportors
336
PPP= glucose 6-phosphate-2 pathways
1.) glucose 6 phosphate--> glycolysis--> 2 pyruvate or NADH or 2 ATPs--> lactate dehydrogenase--> Lactate+NAD+
**The second pathway is the Pentose phosphate pathway
2.) 1. glucose 6-phosphate--> Glucose 6 phosphate dehydrogenase--> 2NADP+ to NADPH--> Glutathione reductase--> 3a- 2GSH to GSGS--> 3B. 2GSH--> glutathione peroxidase--> H202 to 2H20
337
OH- is a strong source of
hemolysis
338
ROS is built up
Heiz bodies
339
Pentose phosphate pathway oxidative step one
1.) Glucose 6 phosphate is oxidized with enzyme G6PDH and NADP to NADPH---> 6- phosphogluconolacetate
340
The pentose phosphate pathway is divided into two steps
Oxidative and non-oxidative
341
PPP step three oxidative
6-phosphogluconate with enzyme 6-phosphogluconate DH with NADP+, NADPH, CO2----> Ribulose 5-phosphate
342
Ribulose-5 phosphate oxidative to
Non oxidative reactions
343
PPP oxidative step two
6 phosphogluconolactone is hydrolized( h20-->OH+H) with enzyme gluconolactonase ---> 6 phosphogluconate.
344
step one of PPP oxidative in word form
G-6-P is oxidized to 6-phosphogluconolactone by G-6-PDH
- 1 molecule of NADPH is generated by reducing NADP
345
Step two of PPP oxidative in word form
The lactone is hydrolyzed by a lactonase to 6-phosphogluconate
346
Step three of PPP oxidative in word form
6-phosphogluconate is oxidatively decarboxylated
by 6-phosphogluonate dehydrogenase to ribulose-5-phophate and CO2
And an additional molecule of NADPH
347
Step 4,5,6 PPP oxidative in word form
4) Ribulose-5-P Ribose-5-P [Phosphopentose isomerase]DNA and RNA synthesis
5) Unneeded ribose-5-Ps are recycled back to hexose-6-Ps thought a series transketolase & transaldolase- catalyzed reactions
6) The resulting hexose phosphates are either recycled through the pentose phosphate pathway or through glycolysis
348
Non oxidative PPP
recycled pathway
349
PPP non oxidative steps
ribose 5 P made and goes to DNA and RNA synthesis
- if we don't need Ribose 5 P then R5P goes to Glyceraldehyde 3 P in step 6 of Glycolysis
- Fructose 6 P can go to step 2 in Glycolysis
- glucose 6 P can go to step one of glycolysis
350
Non-oxidative steps of PPPcan be connected to the
glycolytic pathway
351
activators of TCA enzymes
Substrates, AMP and ADP, and NAD+
352
Oxaloacetate is really important for gluconeogenesis
Oxaloactate--> PEP--> either AA or glucose
353
TCA cycle- Pyruvate---> oxaloacetate is catalyzed by what
ATP dependent reaction with pyruvate carboxylase
354
what activates Pyruvate carboxylase
Biotin and acetyl coA
355
Muscle response to exercise
Glycogen synthesis decreased,
glycolysis increased
increased degradation
356
Glycerol phosphate shuttle
1A.(1/2) glucose ---> glyceraldehyde 3 phosphate
2A. Glyceraldehyde 3 phosphate with glyceraldehyde 3PDH---> 1,3 BPG
2B. NAD-->NaDH
2C. glycerol 3 phosphate with glycerol 3 PDH--> DHAP
2D. FAD with glycerol 3 PDH--> FADH2
3A- 1,3 BPG--> pyruvate
4A- pyruvate-->acetyl coA
357
Malate-aspartate shuttle
1A.(1/2) glucose ---> glyceraldehyde 3 phosphate
2A. Glyceraldehyde 3 phosphate with glyceraldehyde 3PDH---> 1,3 BPG
2B. NAD-->NaDH
2C. OAA with MDH enzyme---> Malate
2D. malate-->a-ketoglutarate
3A. 1,3 BPG--> pyruvate
4A. Pyruvate--> Acetyl coA
358
Malate aspartate shuttle and glycerol phosphate Shuttle work under what conditions
Aerobic conditions
359
The Alanine cycle
Glucose—> 2pyruvate—> alanine muscle
Alanine—> pyruvate—> glucose liver
6atps consumed
Alanine—> NH2–> urea
4atps are consumed
