Valenick Carb Metabolism II Flashcards
1
Q
What are the four things that pyruvate can turn into?
A
lactate
acetyl coa
oxaloacetate
alanine
2
Q
How can pyruvate turn into lactate?
A
through reduction
3
Q
How can pyruvate turn into acetyl CoA?
A
oxidative decarboxylation
4
Q
How can pyruvate turn into oxaloacetate?
A
through carboxylation
5
Q
How can pyruvate turn into alanine?
A
through transamination
6
Q
How does glucose turn into pyruvate?
A
through glycolysis
7
Q
Under what conditions does pyruvate dehydrogenase work?
A
aerobic conditions
8
Q
What reaction does pyruvate dehydrogenase participate in?
A
Pyruvate + NAD+ + CoA-SH → Acetyl-CoA + NADH + CO2
C3-> C2 +CO2
9
Q
The reoxidation of (blank) produces the bulk of ATP by OX-Phos.
A
coenzymes
10
Q
What is the first step of turning pyruvate into acetyl coA?
A
moving it into the mitochondria
travels through pore of outter membrane and through pyruvate transporter of inner membrane to get to mito matrix.
11
Q
Once pyruvate enters the mito matrix, what happens to it?
A
it is oxidatively decarboxylated to acetyl co-A
12
Q
What links glycolysis to the TCA cycle?
A
pyruvate dehydrogenase complex
13
Q
Where is pyruvate dehydrogenase and what is it essential for?
A
the mito matrix; for cellular respiration
14
Q
What type of dehydrogenase is pyruvate dehydrogenase? Is it reversible?
A
an alpha ketoacid dehydrogenase
NOOOOOO
15
Q
What makes up the PDH Complex?
A
3 catalytic enzymes and 5 coenzymes
16
Q
What are the three catalytic enzymes that make up the PDH complex?
A
E1 = Pyruvate dehydrogenase (PDH) E2 = Dihydrolipoyl transacetylase (DLTA) E3 = Dihydrolipoyl dehydrogenase (DLDH)
17
Q
What are the five coenzymes that make up the PDH complex?
A
TPP = Thiamine pyrophosphate CoA = Coenzyme A NAD+ = Nicotinamide adenine dinucleotide FAD + = Flavin adenine dinucleotide Lipoamide
18
Q
4 of the 5 coenzymes of the DHP complex need vitamins for synthesis; what are they? TPP? CoA? NAD? FAD? Lipoamide?
A
Thiamine B1 Panthothenic acid B5 Niacin B3 Riboflavin B2 none NOTE: a deficiency of any of these vitamins can impair the pyruvate dehydrogenase reaction
19
Q
In thiamin deficiency (Beriberi), what accumulate after eating lots of carbs and why is this bad?
A
pyruvate, lactate and alanine.
Most pyruvate turns into lactate which leads to lactic acidosis and impaired CNS Function (due to brains dependence on glucose)
20
Q
What are the components of the coenzyme TPP?
A
pyrimidine ring
thiazole ring,
pyrophosphate (diphosphate) functional group.
21
Q
Thiamine pyrophosphate is bound (blank) to the apoprotein.
A
noncovalently
22
Q
TPP acts as a carrier of (blank) and of the hydroxyethyl group that is formed by pyruvate decarboxylation.
A
pyruvate
23
Q
(blank) is required for E2
A
lipoamide
24
Q
(blank) is bound covalently with an amide linkage to a lys residue. It participates as a redox system and carrier of the acetyl group.
A
lipoic acid
25
we synthesize (blank) directly onto the E2 Enzyme and no free lipoic acid is produced.
lipoate
26
What are the components of lipoamide?
lipoic acid, lys residue of E2 and polypeptide chain of E2
27
What is the prosthetic group of DLTA?
lipoamide
28
What is coenzyme A required for?
DLTA
29
What are the components of coenzyme A?
acetyl coA, panthothenic acid (vit B5) and 3 phosphoadenosine diphosphate
30
What 2 coenzymes are required for DLDH?
NAD and FAD
31
What does this describe?
A hydroxyl group of pantothenic acid is joined to a modified ADP moiety by a phosphate ester bond, and its carboxyl group is attached to β-mercaptoethylamine in amide linkage.
The hydroxyl group at the 3′ position of the ADP moiety has a phosphoryl group not present in free ADP.
The -SH group of the mercaptoethylamine moiety forms a thioester with acetate in Acetyl-CoA.
Coenzyme A
32
What participates in hydride transfers?
| What participates in electron transfers?
NAD+
| FAD
33
what are the components of NAD+?
adenine, di phosphate, Niacin (vit B3)
34
What are the components of FAD?
adenine, di phosphate, riboflavin (vit B2)
35
What are 2 enzymes found tethered to the PDH complex? What do these enzymes do? Phosphorylation causes what?
PDH kinase (4 isoforms) and PDH phosphatase (2 isoforms)
They regulate PDH activity through reversible covalent phosphorylation
inactivation of PDH
36
Complete glucose oxidation begins where and ends where?
begins in the cytoplasm
| ends in the mitochondria
37
Describe the steps of complete glucose oxidation
D glucose->glycolysis->2 pyruvate -> PDH-> 2 acetyl CoA->TCA-> 4 CO2
38
Is there an 02 requirement for glycolysis?
| Is there an O2 requirement for pyruvate dehydrenase plus TCA cycle activity?
no
| yes
39
The catabolic pathways convert the carbon of substrates to (blank)
carbon dioxide
40
The hydrogen initially is transferrred to the coenzymes NAD+ and FAD. The reduced coenzymes then are reoxidized by the respiratory chain. Most of the ATP is produced in the process of (Blank), which couples the oxidation of the reduced coenzymes to ATP synthesis.
oxidative phosphorylation
41
(blank) is the gateway to oxidative metabolism of the food we eat.
acetyl coA
42
What four things can make acetyl coa?
AA, FA, Ketones, Pyruvate
43
explain how you can start with glucose and get to reduced coenzymes?
glucose->pyruvate->acetyl CoA-> TCA-> reduced coenzymes
44
For the generation of metabolic energy, all major nutrients are degraded to (blank). These include carbs, fats, protein and alchol.
acetyl CoA
45
What can Acetyl Co A become?
acetylated products, cholesterol, ketone bodies, fatty acids, into the TCA cycle
46
What is the final common pathway for the oxidation of all major nutrients.
TCA cycle
47
What are the irreversible steps of the TCA cycle?
isocitrate dehydrogenase
Alpha-ketoglutarate dehydrogenase complex
citrate synthase
48
What is the limiting step of the TCA cycle?
oxaloacetate
49
What two steps of the TCA cycle can leave the mitochondria?
citrate, malate
50
What step of the TCA cycle is bound to the inner mitochondrial membrane?
succinate dehydrogenase
51
What three steps of the TCA cycle give off NADH?
isocitrate dehydrogenase
alpha ketoglutarate dehydrogenase complex
malate dehydrogenase
52
To balance the two carbons of acetyl-CoA that enter the TCA cycle, each turn of the cycle releases two carbons as (blank). THe hydrogen in the substrate does not form water, but is transferred to the coenzymes (blank) and (blank).
carbon dioxide
| NAD+ and FAD
53
How many molecules of NADH and FADH2 are formed in each turn of the cycle?
3 of NADH
| 1 of FADH2
54
The energy yield of the TCA cycle is about (blank) ATP for NADH oxidation and (blank) ATP for FADH2 oxidation.
3
| 2
55
Therefore the overall energy yield from the oxidation of one acetyl residue is (blank) high-energy phosphate bonds: one from substrate-level phosphorylation and 11 by the reoxidation of the reduced coenzymes.
12
56
Where in the TCA cycle do you produce ATP (GTP)?
succinate dehydrogenase
57
The efficiency of glucose oxidation is close to (blank) percent.
40%.
58
What are the sources of blood glucose?
food
glycogen degredation (liver)
gluconeogenesis (liver and kidney)
59
What is the only source of glucose during prolonged fasting?
liver
60
How does the liver and kidney make glucose?
during gluconeogenesis using AAs, lactate and glycerol
61
(blank) is the net synthesis or formation of glucose from non-carbohydrate substrates.
gluconeogenesis
62
gluconeogenesis produces glucose from (blank x 3)
amino acids, lactic acid, glycerol
63
liver gluconeogenesis is linked to glycolysis in other (blank)
tissues
64
Both the (blank) cycle and the (blank) cycle depend on gluconegenesis in the liver followed by delivery of glucose and its use in a peripheral tissues
cori cycle
| alanine cycle
65
What are the three irreversible steps of glycolysis?
| During gluconeogenesis, how do you bypass these irreversible steps?
glucokinase
phosphofructokinase 1
pyruvate kinase
by using different enzymes
66
What are the different enzymes used to bypass the irreversible steps of gluconeogenesis? And where are these reactions taking place?
1) pyruvate carboxylase (Mitochondria) and PEP carboxykinase (cytoplasm or mitochondria) bypass pyruvate kinase
2) Fructuse 1,6 bisphosphate (cytoplasm) bypasses phosphofructokinase 1
3) Glucose 6 phosphatase (ER) bypasses glucokinase
67
What pushes all the other reversible steps in the gluconeogenesis pathway?
mass action
68
What enzyme is biotin dependent?
pyruvate carboxylase
69
PEP is transported across the inner mitochondrial membrane, whereas (blank) is shuttled into the cytoplasm after being reduced to malate or transaminated to aspartate.
oxaloacetate
70
Since the pyruvate kinase reaction of glycolysis is irreversible two enzymes (pyruvate carboxylase and PEP carboxykinase) must bypass this step at what cost? What is the driving force behind this?
```
1 ATP and 1 GTP per pyruvate molecule
Driving force: greater concentration of:
ATP than ADP
GTP than GDP
Pruvate than PEP
```
71
The other two irreversible steps of glycolysis that must be bypassed for gluconeogenesis are PFK and hexokinase. THese are bypassed via F1,6BP and G6P, How does these ezymes accomplish this?
hydrolytic removal of phosphate
72
(blank) is caused by a defect in Glucose 6-Phosphatase or the Glucose 6-phosphate transporter in the ER membrane.
Von Gierke's disease
73
What three transporters are involved in the third bypass (G6pase) of gluconeogenesis?
one moves g6p into lumen
one moves phosphate to cytoplasm
one moves glucose to cytoplasm
74
Lactate generates a (blank) when it is converted to pyruvate. Is there a net loss of NADH in gluconeogenesis from lactate?
NADH
| No
75
Lactate (cory cycle) and alanine (alanine cycle) are convenient substrates of gluconeogenesis because they are readily converted to pyruvate by (blank) and (blank)
lactate dehydrogenase and transamination
76
Explain how the cori cycle works with gluconeogenesis?
| What is the difference between the cori cycle and the alanine cycle?
you start with lactate-> pyruvate-> go into mitochondria to make OAA-> shuttle OAA out of mito or convert OAA to PEP and then shuttle out of mito-> continue process in cytosol->G6P gets its phosphate taken by G6Pase in the ER-> GLUCOSE :)
Alanine will be converted into pyruvate instead of lactate
77
Gluconeogenesis must run (blank) times to produce one glucose
2 times
78
What does glucagon do?
makes glucose!!!!!
79
What does insulin do?
gets rid of glucose!!!
80
Does it cost any ATP to convert alanine to pyruvate?
| What does it cost to turn lactate into pyruvate?
no!
| nothing, you actually gain 2 NADH's so it costs less energy to make lactate than pyruvate
81
Most tissues glycolyze (undergo glycolysis) after a carbohydrate meal but switch to (blank) during fasting.
fatty acid oxidation
82
it is mandatory to control the irreversible reactions at all three bypasses to ensure that only the glycolytic reactions or only the gluconeogenic reactions take place, but not both.
Therefore, F2,6 BP is regulated by (blank)
hormones
83
F2,6 BP stimulates (blank) and inhibits (blank)
glycolysis
| gluconeogenesis
84
(blank) fine-tune glycolysis and gluconeogenesis in the liver.
effectors
85
The levels of (blank) and (blank) are elevated during fasting because of fatty acid oxidation. Therefore, they stimulate gluconeogenesis.
ATP, acetyl-CoA
86
(blank) is the most important regulated enzyme in the PEP-pyruvate cycle.
pyruvate kinase
87
What is an activator for pyruvate kinase? What is an inhibitor of pyruvate kinase?
F1,6 BP
| ATp, Alanine, glucagon
88
What is an activator for pyruvate carboxylase? What is an inhibitor of it?
acetyl CoA
| ADP
89
What is an activator of PFK1? What is an inhibitor of it?
F2,6 BP
| ATP, citrate
90
(blank) turns ON glycolysis and OFF gluconeogenesis (hormonally regulated).
F2,6bis-P
91
In general, (blank) and (blank) increase the levels of glycolytic enzymes, whereas glucagon and fatty acids have the opposite effect.
insulin and glucose
92
(blank) rises in response to low blood glucose during fasting. It reduces glucose consumption and stimulates glucose production by the liver.
glucagon
93
(blank) signal to increase blood glucose. They lead to phosphorylation of key regulatory enzymes in a pathway. So when you think of phosphorylation you think of these.
glucagon and epinephrine
94
(blank) signal to decrease blood glucose. This changes the expression of regulatory enzymes,reduces phosphorylation of enzymes and modulates the localization of reguated steps.
insulin
95
(blank) is released from pancreatic alpha cells
| (blank) is released from pancreatic beta cells during hyperglycemia.
glucagon
| insulin
96
Describe the G-protein coupled receptor signaling
| Is there signal amplification?
```
hormone binds receptor
GDP is released-> GTP binds.
Gq translocates to adenylate cyclase
Second messenger cAMP is generated
PKA is activated
regulated proteins get phosphorylated
```
YES!
97
(blank) regulates pyruvate kinase in the liver, if glucagon works on pyruvate kinase it will phosphorylate it rendering it (Blank)
glucagon
| inactive!
98
If you inactivat pyruvate kinase, PEP cannot reenter (blank)
glycolysis
99
The amount of F2,6BP is regulated by (blank)
hormones
100
F2,6 BP is a competitive inhibitor of (blank) and an allosteric effector of (blank). SOOO you can think of F2,6 BP as being glycolysis loving and gluconeogenesis hating!
F1,6 bisphosphatase
| PFK1
101
In humans, only the (blank) has glucagon receptors
liver
102
Kinase favors (blank) while phosphatase favors (blank)
glycolysis
| gluconeogenesis
103
(blank) makes more F6P while (blank) makes F26BP
gluconeogenesis
| glycolysis
104
How is phosphoprotein phosphatase (the enzyme that promotes glycolysis) inhibited and what does it do?
phosphoprotein phosphatase allows F6P to turn into F 2,6 BP to promote glycolysis. It is inhibited by glucagon by the PPP inhibitor being phosphorylated.
105
PFK2-F2 F2,6 Bpase( the enzyme that converts F2,6 BP to F6P) decreases the concenrtation of (blank) when it is phosphorylated.
F2,6 BP
106
PFK2 F2,6 BPase is an enzyme with a dual function. When this enzyme is phosphorylated it works as a (blank). When it is dephosphorylated,i it works as a (Blank)
phosphatase
| kinase
107
When PFK2-F2,6BPase is phosphorylated, the level of fructose 6 phosphate is increased turning on gluconeogenesis and slowing glycolysis. During this time, the liver generates energy from (blank)
fatty acid oxidation.
108
After a good meal, insulin cAMP->AMP and PFK2-F2,6Bpase acts as a (blank), and stimulated (Blank).
kinase
| glycolysis
109
Insulin regulates gene expression, and it reduces the cyclic AMP (cAMP) level in the liver by activating a cAMP-degrading phosphodiesterase. This decreases the phosphorylation of Phosphofructokinase 2-Fructose2.6 bisphosphatase leading to an increase of (blank). This stimulates glycolysis and inhibits gluconeogenesis.
fructose 2,6 bisphosphate
110
F2,6BP stimulates PFK1 (glycolysis)and inhibits (blank)
F1,6 BPase
111
What all does insulin increase?
PFK1, PFK2, pyruvate kinase expression
112
(blank) are long term effectors and stimulate gluconeogenesis by inducing the synthesis of gluconeogenic enzymes..
glucocorticoids
113
(blank) are released during sustained stress. They stimulate gluconeogenesis by inducing the synthesis of gluconeogenic enzymes.
The hormones regulate the synthesis of the distinctive glycolytic and gluconeogenic enzymes at the level of transcription. Because this involves the synthesis of new enzyme protein and most of the enzymes have lifespans of a few days in the cell, regulation of enzyme synthesis works on a time scale of days rather than minutes.
glucocorticoids
114
Besides carbs, what else can be glucogenic (make glucose)?
Lactate, Alanine, all other AAs except for leucine and lysine, Glycerol, ODD chain fatty acids.
115
Glycerol, derived from triglyceride hydrolysis in adipose tissue, enters gluconeogenesis (and glycolysis) through (blank) at the level of the (blank) phosphates
DHAP
| triose
116
(blank) is not only a gluconeogenic intermediate but also a member of the TCA cycle. THis is important so that TCA cycle intermediates can enter gluconeogenesis at this point.
Oxaloacetate
117
Can acetyl coenzyme A be converted to glucose?
no
118
The (blank) reaction is irreversible, and there are no alternative reactions to channel acetyl-coA into gluconeogenesis. (blank) are degraded to acetyl coA. Therefore the ones that are released from adipose tissue during fasting cannot be turned into glucose.
pyruvate dehydrogenase reaction
| Fatty acids
119
(blank) depends on amino acids and, to a lesser extent, on lactic acid and glycerol.
Gluconeogenesis
120
WHy can odd chain fatty acids become glucose but even cant?
because odd have an extra carbon so it can become pyruvate
121
Although (blank) enters the TCA cycle, it is not a substrate of gluconeogenesis because the citrate synthase reaction does not involve the net synthesis of a TCA cycle intermediate.
acetyl-CoA
122
Describe the process of ethanol degredation
ethanol->acetaldehyde->acetate->acetyl CoA
123
What are the enzymes involved in ethanol degredation and where are they located?
alcohol dehydrogenase complex (cytoplasm)
aldehyde dehydrogenase (mitochondrial)
acetyl CoA synthase (mito in muscle, cytoplasm)
124
What are the products of ethanol degredation?
NADH, ATP
125
Where does most of the acetate from ethanol degredation go?
most goes into the blood where it is oxidized by the liver
126
What is this?
| H3C-CH2OH → H3C-CHO → H3C-COO- → Acetyl-CoA
ethanol degredation
127
What is the rate limiting step of alcohol metabolism? How many drinks of alcohol will saturate this enzyme? What is it dependent upon and why order kinetics does this enzyme follow?
ADH (alcohol dehydrogenase)
1!
NAD+ availability
zero
128
Aldehyde dehydrogenase can be inhibited by (blank).
disulfiram (antabuse)
129
How does antabuse work? What is it used for?
it blocks aldehyde dehydrogenase which leads to a build up of aldehyde which makes you sick. Used to treat alcoholism.
130
(blank) accumulates to toxic levels after only 1 or 2 drinks (believed to cause cirrhosis).
Acetaldehyde
131
(blank) is caused by a isoform of the enzyme aldehyde dehydrogenase which results in a higher Km, making it the rate limiting step. This results in build up of acetylaldehyde.
“Oriental Flush”
132
(blank) metabolism is not subject to negative control. THe major products are acetyl CoA, NADH, and ATP.
ethanol
133
Ethanol metabolism inhibits what process by inhibiting which enzymes?
glycolysis
| PFK1 and PDH
134
During ethanol metabolism, beta oxidation and high NADH levels shut down both beta-oxidation of (blank) and the (blank).
fatty acids
| TCA cycle
135
Durin alcohol metabolism you end up with excess NADH, what does it do to your body?
Makes LDH reaction irreversible and lactic acid accumulates and is released into the blood
136
What are the two components that alcohol can be broken into?
ketones and fatty acids
137
In the liver, what happens to acetate?
In the cytoplasm it is converted to acetyl coa and then to ketones
138
Can ketones be metabolized by the liver, and why do they do to plasma pH?
NO
| decreases it resulting in acidosis (ketoacidosis)
139
Alcohol is (blank), not glucogenic
ketogenic
140
Following the consumption of ethanol, acetate levels can be elevated by as much as (blank)
20 fold.
141
In alcohol metabolism, the fatty acid oxidation is (blank), therefore acetyl coA generated is diverted to ketones and fatty acid synthesis.
inhibited
142
What is the primary cause of fatty liver syndrome?
the build up of fatty acids in the liver due to the shut down of fatty acid oxidation. These fatty acids are esterified and triglycerides synthesized and exported as VLDL (bad cholesterol)
143
Most Acetate from alcohol metabolism leaves the liver and is metabolized by (blank) and (blank) (contain high levels of mitochondrial Acetyl CoA synthase) generating Acetyl CoA.
heart and skeletal muscle
144
Why doesnt the liver metabolize ketones?
because the liver doesnt have SCOT (acetoacetate succinyl Coa Transferase) ....other tissues do
145
(blank) disrupts vitamin metabolism.
ethanol
146
Ethanol is a competitive inhibitor of retinol dehydrogenase thereby disrupting the metabolism of which vitamin?
vitamin A (retinol)
147
Ethanol decreases the absorption of what vitamin?
Vitamin B1 (thiamine)
148
What disease can B1 deficiency cause?
Wernick-Korksakoff syndrome (brain damage)
149
(blank) results from damage to areas of the brain involved with memory.
Korsakoff psychosis
150
(blank) is caused by brain damage in the thalamus and hypothalamus.
Wernicke's encephalopathy
151
What does this describe:
| In males metabolism begins in the stomach wall, but in general most of the metabolism takes place in the liver.
ethanol
152
(blank) is an intoxicant and energy source
ethanol
153
Being a water-miscible organic solvent, (blank) rapidly distributes through the aqueous compartments of the body, with tissue concentrations similar to the blood alcohol level.
ethanol
154
Ethanol leads to excess NADH which favors (blank), depletes (blank), stops (blank), favors (blank) so it depletes OAA.
lactate (acidosis)
Pyruvate
TCA cycle
malate
155
Ethanol makes gluconeogenesis becomes impossible, so if liver glycogen levels are low,what can result?
hypoglycemia and increase in G3P and fatty acids, increase in triacylglycerides and increase in VLDL, and slows fatty acid oxidation
156
Unlike most metabolic pathways, alcohol metabolism is not (blank). Therefore, alcohol is metabolized over the oxidation of other nutrients.
negatively regulated.
157
What are the three stages of liver damage?
fatty liver from increased TAG synthesis
alcoholic hepatitis : liver inflammation caused by drinking
cirrhosis: hepatocytes due and there is replacement fibrosis
