Lecture I & II Flashcards
1
Q
What is metabolism?
A
Series of chemical reactions in which foodstuff is converted to usable energy forms. Can be catabolism or anabolism
2
Q
What is catabolism?
A
Breakdown of complex organic molecules into simple molecules
Process releases ATP
3
Q
What is anabolism?
A
Assebly of simple molecules into complex organic molecules
Requires use of ATP/energy
4
Q
How does ATP create energy?
A
Cleaving third phosphate in energetically favorable reaction forming ADP
Forming ATP is not energetically favorable
Reaction is hydrolysis leaving ADP and inorganic phosphate behind
5
Q
What is oxidation?
A
Loss of electron from atom as a result of adding oxygen or removing hydrogen
6
Q
What is reduction?
A
Gain of electron resulting from gain of hydroden or loss of oxygen
7
Q
What are the most important electron transporters?
A
NAD+ and NADP+
These are oxidized forms of NADPH and NADH
NAD+/NADP+ are oxidizing agents
8
Q
Difference between NADP & NAD?
A
Phosphate group at the 2 prime position of ribose ring
9
Q
What does drinking alcohol to to NAD+ in body?
A
Removes it from the system to it can no longer be used in glycolysis
This is why drinking makes you feel so hungry even though glucose is high
10
Q
What must carbohydrates be converted into?
A
Fructose
Glucose
Galactose
11
Q
What must lipids be converted into?
A
Glycerol and fatty acids
12
Q
Where can proteins enter metabolic cycle?
A
Pyruvate
AcCoA
TCA
13
Q
Where can lipids enter metabolic cycle?
A
Pyruvate
AcCoA
14
Q
Main function of AcCoA?
A
Convey carbon atoms from acetyl groups to TCA
15
Q
Where is AcCoA generated?
A
Micohondrial matrix
16
Q
What can give rise to AcCoA?
A
Proteins, carbs, and lipids
17
Q
4 Fates of AcCoA?
A
Lipogenesis
TCA
Ketone Bodies
Cholesterol
18
Q
Primary fate of AcCoA?
A
TCA
Oxidation of acetyl groups in a combustion reaction producting water, CO2, ATP
19
Q
What is lipogenesis?
A
Formation of fatty acids from AcCoA, carbs or Aas
20
Q
What is esterification?
A
Formation of triacylglycerol (fats) from fatty acids
21
Q
Where does glycolosis occur?
A
Cytoplasm
22
Q
What is ketogenesis?
A
Formation of ketone bodies from AcCoA
23
Q
What is cholesterogenesis?
A
Formation of cholesterol from AcCoA
Chosterol can then be converted to steroids
24
Q
What is steroidogenesis?
A
Creation of steroids from cholesterol
25
What dietary items can fat storage?
Proteins, carbs, and lipids as they can all become AcCoA then become fat via lipogenesis and esterification
26
What is Beta Oxidation?
Creating AcCoA from Fatty acids
27
Primary metabolization of carbs?
As glucose, fructose and galactose become intermediates in glycolytic pathway
28
What has largest glycogen stores?
Liver, heart, skeletal muscle
29
Where does beta oxidation occur?
Mitochondria forming AcCoA from fatty acids
| Only cells with mitochondria can perform this
30
What are triacylglyerols?
Stored form of fatty acids in adipose tissue
31
What does protein metabolism yield?
NH4 (ammonia)
| Toxic in large amounts so liver must turn into urea
32
Preffered fuel of Liver?
Fatty Acids
Glucose
Amino Acids
33
Preffered fuel of Adipose Tissue?
Fatty Acids
34
Preffered fuel of skeletal muscle?
Glucose under exertion
| Fatty acids at rest
35
Preffered fuel of heart muscle?
Fatty acids
36
Prefferred fuel of brain?
Normally glucose but can also use ketone bodies in starvation
37
What does liver do while fasting?
Uses energy to create glucose from fatty acids
38
What occurs in fasted state?
Low insulin initiates lypolisis in adipose tissue increasing serum fatty acids
Fatty acids used preferentially by some tissues or converted to glucose by liver
39
What happens to AcCoA generated from fatty acid oxidation in liver?
Oxidized to form ketone bodies in liver mitochondria
| Brain will use these when levels are high enough but still always needs glucose
40
How many calories does a gram of fat provide?
9 Kilo cals
41
How many calories does a gram of carbs provide?
4 Kilo cals
42
How many calories does a gram of protein provide?
4 Kilo cals
43
Amylose source and enzyme?
Potatoes, rice, corn, bread
| Maltase
44
Sucrose source and enzyme?
Table sugar & desserts
| Sucrase
45
Lactose source and enzyme?
Milk products
| Lactase
46
Fructose source and enzyme?
Fruit & Honey
47
Glucose source and enyme?
Fruit Honey & Grapes
48
What does maltase do?
Digests amylose
49
What is starch?
Polymer of glucose which is form most foods enter body
50
What digests starches?
Amylase in pancreas and saliva
51
What is sucrose?
Glucose/fructose molecule
52
What is lactose?
Galactose and glucose molecule
53
Where are disaccharides digested?
Brush border of smal lintestine
| Final digestion of them occurs on luminal surface of SI epithelial cells
54
Can disaccharides be absorbed?
No
55
What must acids be turned into to enter TCA?
Alpha keto acids
56
What is lactose intolerance?
Decrease in intestinal lactase prohibiting lactose from being absorbed
Causes water to follow lactose leading to diarrhea
Gut bacteria also digests into gases causing bloating
57
What can be confused with lactose intolerance?
Milk alergy induced anaphylaxis
58
What does insulin do and where is it produced?
Pancreatic beta cells
Promotes glycolysis and glycogen sysnthesis
Main function is to keep blood sugar low
59
What is glucagon and where is it made?
Pancreatic alpha cells
| Causes liver to release glucose into blood via glycogenolysis
60
What is glycogenolysis?
Break down of glycogen by liver and muscle cells
61
What enzyme is used to convert glycogen in muscles?
Glycogen phosphorylase
62
What does glycolysis create?
Single glucose molecule yields 2 ATP, 2 Pyruvate 2 molecules water and 2 molecules NADH
63
What is gluconeogenesis?
Creation of glucose from con carbohydrate sources such as pyruvate, lactate, glycerol, and glucogenic Aas
64
Bodies glucose requirements?
Brain: 120g per day
Muscles: 40g per day
65
What must blood glucose be kept above to keep brain functioning?
6omg/100ml
66
What is chronic hyperglycemia?
Blood glucose above 110mg/100ml
67
What happens in fed state?
Glycogen storage
Insulin release
ATP production via pyruvate and lactate production
AcCoA or tiacylglycerol can be created
68
What are serum levels like just after eating?
High glucose and insulin
| Low glucagon, fatty acids, and ketones low
69
Where is epinephrine release from?
Adrenal medulla
70
Are there glucagon receptors on liver?
No
71
What does the pentose phosphate pathway produce?
NADPH
72
What is protein in milk causing allergy?
S1 Casein
73
What is product of Glycogenlysis?
Glucose-6-P
74
What does adding phosphate to glucose do?
Traps it in cell
75
What is Oxaloacetate use for?
To create glucose-6-P in gluconeogenesis
76
What do epinephrine and glucagon do?
Block glycolyis and encourage gluconeogenesis to keep blook leves high
77
Can glucose be created from lactate and pyruvate?
From lactate by not pyruvate
78
What is special of RBC metabolism?
No mitochondria
Only can metabolize carbs no proteins or fats
Lactace made as no mitochondria and is released from cell
Pentose phosphate pathway prevalent
79
Brain metabolism?
Pentose phosphate pathway
Nearly all glucose in TCA
Very small glycogen store
80
Muscle metabolism?
TCA
Pentose pathway
Glycogen stores but only to be used by cell not sent into circulation
81
Adipose metabolism?
No TCA
| Excess glucose becomes fats
82
Liver metabolims?
```
Pentose
TCA
Gluconeogenesis
Glucogen synthesis
Glucogenolysis for body
Glucouronide production
```
83
What are glucouronide?
Produced in liver
| Responsible for drug and bilirubin detoxification
84
SGLTI
One molecule of glucose or galactose with 2Na
Na fructose
Found in intestinal mucosa and kidney tubule
Down gradient
85
SGLT2
One glucose and 1 Na
Found in kidney tubule
No galactose or glucose
Down gradient
86
Glut2
```
Low affinity, high Km
Inulin independent
Liver intestines, kidney
Moves in both directions: into cell in fed out, out in starved
Serves as glucose sensor in beta cells
```
87
Glut4
```
Insulin Dependent
High glucose affinity, low KM
Heart, mucle, adipose
Not active during resting state
Gets glucose after we have eaten
```
88
What does glucokinase do?
Turns glucose into glucose 6 phosphate trapping it in cell
89
What does gluco-6 phosphotase do?
Removes phosphate from glucose allowing it to leave cell in starved state
90
What enzyme is found with GLUT4?
Hexokinase
91
What enzyme is found with GLUT2?
Glucokinase
92
Important steps in glycolysis?
Priming step - ATP invested to break glucose
Splitting stage
Ox/redox stage
93
What happens in splitting stage?
Fructose-1-6 bisphosphate split into either dihydroxyacetone phosphate or glyceraldehyde 3 phosphate
94
What does Aldolase do?
Enzyme responsible for splitting fructose-1-6 bisphosphate into dihydroxyacetone phosphate
95
What happens in the Ox/redux / phosphorylation stage?
- Glyceraldehyde 3 phosphate converted into pyruvate - and ATP
- ATP earning
- NADH is created during this step
96
What are the 3 key glycolytic enzymes?
1. Hexokinase /glucokinase
2. PFK1
3. Pyruvate kinase
97
What does Hexokinase / glucokinase do?
- Regulates change of glucose to glucose-6-P
- This is a phosphorylating enzyme
- Hexokinase found in muscle cells, glucokinase in liver
98
What does PFK1 do?
- Regulates change of fructose-6-P to Fructose-1-6 bisphosphate
- This is a phosphorylating enzyme
- PFKI - can be regulated by PFKII
99
What does Pyruvate kinase do?
- Regulates change of phosphoenolpyruvate to pyruvate
| Substrate level phosphorylation
100
How many ATP does glycolysis create?
4 total
| 2 net
101
What happens to pyruvate when energy is not needed?
Becomes substrate in aa synthesis
102
What are the ways in which enzymes can be modulated?
1. Allosteric regulation
2. Covalent modification
3. Induction/repression of gene
103
What is covalent modification?
Kinases - phosphorylate
| Phosphotases - dephosphorylate
104
Where is hexokinase found? What regulates it? When is it present?
All cell types
Modulated by product, glucose-6-P
Always present and non inducible
105
What is km of hexokinase?
Very low, easily saturated
106
Where is glucokinase found? How is it moldulated
Present in liver and pancreas
| Active when moved to cytoplasm, inactive in nucleus
107
What regulates glucokinase?
Glucose - increases
Insulin - increases
Fructose 6 - P: decreases
108
What is KM of glucokinase?
High, not easily saturated
109
What happens in irreversible rxn 1?
- Glucose becomes glucose-6-p locking it in cell
| - ATP required
110
What positively regulates PFK1?
ADP
AMP
Fructose-2-6 biphosphate
111
What negatively regulates PFK1?
ATP
| Citrate
112
What does fructose 2-6 biphosphate regulate?
Hepatic PFKI
113
What does PFKII do? When does it do this?
Converts fructose-6-P to Fructose-2-6-P in liver
| Occurs when insulin and glucose and high and more glycolysis is needed
114
How is hepatic fructose-2-6-P regulated?
Inhibitors - epinephrine & glucagon
Stimulate cAMP & PKA
These inhibit kinase domain of PFKII stopping F26P formation and stopping glycolyis
115
Can PFKI function without F26P?
No! In absence glycolysis is stopped and gluconeogenesis occurs
116
What is different about glycolysis in the heart, skeletal muscle?
- Epinephrine activates phosphotase region of PFKII activating enzyme and stimulating glycolysis
- No glycogen receptors
117
What does phosphorylation of hepatic PFKII do?
Inactivates it
118
What regulatory means are used in hepatic PFKII?
Hepatic glycolysis is inhibited by epinephrine and glucagon through inhibition of enzymes and repressed mRNA synthesis
119
What inhibitis and encourages pyruvate kinase?
Activated: insulin and fructose-1-6-P
Inhibition: epinephrine, alanine, and ATP, glucagon
120
What does pyruvate kinase do?
- Converts phosphoenolpyruvate into pyruvate
121
What form of pyruvate kinase is active?
Phosphorylated form is less active
122
What does lack of pyruvate kinase cause?
Hemolytic anemia
123
What can pyruvate become?
Lactate
AcCoA
Alanine
AxaloacetateW
124
What does Pyruvate dehydrogenase do?
Key enzyme for entering TCA cycle by converting pyruvate to AcoA
125
What is microcephally?
- reduced head circumference
126
Symptoms of pyruvate dehydrogenase defect?
Microcephaly, poor muscle coordination, mental retardation
127
What does Pyruvate carboxylase do?
- Converts pyruvate to oxaloacetate
128
Where are glucagon receptors located?
In liver and not on muscles as only liver metabolizes glucagon for rest of body
129
What does inhibition of Hepatic glycolysis do?
Preserves glucose for use by tissues that have fuel prefference
130
What type of cells have epinephrine receptors?
Liver, muscle, fat
131
How do epinephrine and glucagon control glycolysis?
Indirectly inhibiting PFKI
Directly inhibiting pyruvate kinase
In liver they also slow synthesis of three required enzymes
132
What does gyclolysis require? How do we get it?
NAD+
| NADH is oxidized in conversion of pyruvate to lactate by LDH
133
How can NAD be regeneraed?
Conversion of pyruvate to lactate by LDH
| Mitochondrial linked shuttles
134
What does LDH do?
- Enzyme in body that controls conversion of pyruvate and NADH to lactate and NAD+
135
What is LDH5-M4? -
Specific LDH molecule in skeletal muscle that preferentially converts pyruvate to lactate to give energy burst during exercise
136
What is LDH1-4H?
- LDH enzyme in heart prefers to convert lactate to pyruvate
- Allows for prolonged energy creation
137
What is normal lactate/pyruvate ratio?
Normal serum concentration of lactate:pyruvate is 10:1
138
What does Pyruvate dehydrogenase do?
- Multienzyme complex that converts pyruvate, NAD+ and coenzyme A to AcCoA in the mitochondrial matrix
139
What are pyruvate dehydrogenase cofactors?
- Thiamine, riboflavin, niacin increase PDH function
| - These are B1, B2, B3, B5
140
What happens if you do not have pyruvate dehydrogenase cofactors?
Limited movement from pyruvate to AcCoA but you can still have AcCoA from fatty acids and proteins
141
What regulates PDH?
- End products (AcCoA & NADH) allosterically inhibit PDH function by phosphorylation
- Glucagon and Epinephrine play no role
- Increased Mg and Ca function to increase activity of PDH via phosphatase action
- Usually present in increased activity
142
What happens in lactate dehydrogenase deficiency?
- Lack of LDH limits NAD+ levels during exercise so little pyruvate can be created from lactate to undergo glycolysis
- Moderate exercise cannot be maintained due to lack of energy
- Must be homozygous to see effects
143
Inputs and outputs of glycolysis?
Inputs - Glucose, 2 ATP, 4 ADP, 4 P, 2 NAD+
Output - 4 ATP, 2 NADH, 2 pyruvate, 2 ADP
Net gain of 2 ATP
One glucose yields 2 pyruvate
144
Do RBCs make pyruvate?
- RBCs only make lactate as they do not have mitochondria
145
What reactions require oxygen?
Reoxidation of mitochondrial NADH formed in reaction catalyzed by PDH
Reoxidation of cytosolic NADH by mitochondrial linked shuttle
Glycerol phosphate shuttle
Malate aspartate shuttle
146
What do low levels of NADH Do?
Low levels of NADH decrease the formation of lactate
147
Enzymes required for galactose metabolism?
Galactokinase - converts galactose to galactose 1-P
Gal-1-P uridyltransferase - converts galactose 1 - P to glucose 1-p
Then converted to glucose-6-p by hexo/glucokinase
148
What does Galactokinase do?
- converts galactose to galactose 1-P
149
What does Gal-1-P uridyltransferase?
- converts galactose 1 - P to glucose 1-p
150
What does lactose become?
Glucose and galactose
151
What is Galactosemia?
- genetic (autosomal recessive) disorder caused by lack of galactokinase and Gal-1P uridyltransferase leading to buildup of Galactitol and galactose 1-P
152
Which form of galactosemia is more sever?
Gal-1P uridyltransferase - more common
153
Symptoms of galactosemia?
- Symptoms: include cataracts, jaundice, brain & kidney damage, enlarged liver, galactosuria
- In deficiency of galactokinase only galactose urea, cataracts, and galactosemia are seen
154
What is Galactitol?
What builds up in body when galactokinase is not present
155
What is required for fructose metabolism?
Fructokinase - turns fructose into frutcose-1-P
| Aldolase A/B/C - convert fructose-1-P into glyceraldehyde 3 phosphate or dihydroxy acetone phosphate
156
What is special about aldolase B?
Found in liver and RBCs, plays crucial role in glycolysis and gluconeogenesis
157
Symptoms of fructose metabolism issues?
```
Hypoglycemia
Vomiting
Jaundice
Hepatic failure
Causes accululatoin of fructose which is toxic and hypoglycemia
Increases lactic and uric acid
```
