Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

M1 > Integration of Metabolism > Flashcards

Integration of Metabolism Flashcards

1
Q

What are the three controlling elements that determine whether fuel is metabolized or stored?

A

Hormones

Concentration of available fuels

Energy needs of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hormonal regulation of carbohydrate and lipid metabolism

A

Insulin:glucagon ratio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

After a meal, glucose can be converted to glycogen or triglycerides in the liver - what is the first step of both metabolic pathways?

A

Conversion of glucose to glucose-6-phosphate by glucokinase

This enzyme is most active in the fed state, when the glucose concentration is high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Synthesis of glucokinase

Hormonal regulation

A

Induced by insulin
Repressed by glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Key regulatory enzyme that converts glucose-6-phosphate to glycogen

A

Glycogen synthase

Activated by dephosphorylation, which occurs when insulin is elevated and glucagon is decreased.

Glycogen synthase is also activated by increased levels of glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

For lipogenesis, glucose-6-phosphate is converted to ______

A

Pyruvate, and eventually acetyl-CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

When is pyruvate DH most active?

A

When it is dephosphorylated

ADP conc. is elevated, products are being converted, and insulin is present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What enzyme catalyzes the conversion of pyruvate to oxaloacetate?

A

Pyruvate carboxylase

Pyruvate carboxylase is activated by acetyl-CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Acetyl-CoA condenses with _____ to form ______

A

Acetyl-CoA condenses with oxaloacetate to form citrate.

When the body has a surplus of energy, the ratio of NADH/NAD+ is high and inhibits isocitrate DH in the mitochondria. This leads to citrate accumulation within the mitochondrial matrix. As citrate continues to accumulate, it is transported into the cytosol to donate carbons for FA synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

The citrate shuttle transports what molecule?

To and from?

A

Acetyl-CoA, from mitochondrial matrix to cytosol (acetyl-CoA cannot diffuse the mitochondrial membranes)

Once in the cytosol, citrate is cleaved by citrate lyase, forming oxaloacetate and acetyl-CoA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What recycles the cytosolic oxaloacetate generated by citrate lyase of the citrate shuttle?

A

Oxaloacetate is recycled to pyruvate via cytosolic malate DH and malic enzyme (generates NADPH for FA synthase complex)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What enzymes produce NADPH?

A

From PPP: glucose-6-phosphate DH (induced by insulin), and 6-phosphogluconate DH

From citrate shuttle: Malic enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Fed/Fasting metabolic changes in the liver

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Acetyl-CoA carboxylase regulation

A

Activated by citrate
Inhibited by long-chain fatty acyl-CoA

A phosphatase stimulated by insulin activates the enzyme by dephosphorylation

Inudction of expression: the quantitiy of the enzyme increases in the fed state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Malonyl-CoA inhibits _____

A

Carnitine:palmitoyltransferase I (CPT I)

In the fed state, when acetyl-CoA carboxylase is active, and malonyl-CoA levels are elevated, newly synthesized
fatty acids are converted to triglycerides for storage rather than being transported into mitochondria for
oxidation and ketone body formation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Insulin stimulates adipose cells to synthesize and secrete ____

A

Lipoprotein lipase (LPL)

LPL hydrolyzes the chylomicron and VLDL triglycerides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What activates lipoprotein lipases (LPLs)?

A

Apolipoprotein (apo) C-II, donated to chylomicrons and VLDL by HDL, activates LPL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

The number of glucose transportes in adipose cell membranes ______ in response to insulin

A

Increase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

The enzymes of glycogen degradation are activated by _____

A

cAMP directed phosphorylation

Glucagon stimulates adnylate cyclase to produce cAMP, which activates protein kinase A - inactivates glycogen synthase

20
Q

What happens when phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase, and glucose-6-phosphatase are induced?

A

Gluconeogenesis is stimulated

Induction is due to protein kinase A (PKA) phosphorylation and activation of a particular set of transcription factors

Fructose 1,6-bisphosphatase is also activated because the levels of its inhibitor, fructose 2,6-bisphosphate, are
low

21
Q

Fasting levels of cAMP in adipose cells

A

Increase

22
Q

What activates hormone-sensitive lipase (HSL)?

A

Glucagon actviates adenylate cyclase to produce cAMP, which activated protein kinase A (PKA).

PKA phosphorylates HSL - activating it to cleave FA’s from tiglycerides

Epi, adrenocorticotropic hormone, and growth hormon also actrivate HSL

23
Q
A
24
Q

In the liver, when acetyl-CoA carboxylase is inactive, malonyl-CoA levels are low, and CPT-I is active, what occurs?

A

Fatty acids are transported into the mitochondria to undergo oxidation

25
Q

What is the fate of acetyl-CoA produced by β-oxidation

A

Acetyl-CoA produced by β-oxidation is converted to ketone bodies

26
Q

Tissue and fuel source

Table

A
27
Q

High levels of acetyl-CoA (from fat oxidation) inhibits _______ and activates ______ which produces _______ for ________

A

High levels of acetyl-CoA (from fat oxidation) inhibits pyruvate DH and activates pyruvate carboxylase, which produces oxaloacetate for gluconeogenesis.

28
Q

When the NADH/NAD+ ratio is high, what is the fate of oxaloacetate?

A

Oxaloacetate is diverted to malate, such that the malate can exit the mitochondria for use in gluconeogenesis.

29
Q

As insulin levels drop, the concentration of what glucose transporters are reduced?

A

GLUT4 - reduces glucose entry from circulation into the muscle

GLUT4 transporters are also induced by high AMP levels through AMP-activated protein kinase

Thus, if energy levels are low and the concentration of AMP increases, glucose can still be transported from the circulation into the muscle to provide energy. This will most frequently be the case during periods of exercise.

  • As fatty acids become available because of increased lipolysis of adipose triglycerides, the exercising muscle begins to oxidize fatty acids.
30
Q

What regulates the switch between anabolic/catabolic pathways?

A
  • The switch between catabolic and anabolic pathways is often regulated by the levels of AMP and fructose 2,6-bisphosphate in cells, particularly the liver.

The rise in AMP signals more energy is required

When blood glucose levels are low, and glucagon is released, PFK-2 is phosphorylated by the cAMP-dependent
protein kinase and is inhibited, which lowers fructose 2,6-bisphosphate levels and inhibits glycolysis while favoring
gluconeogenesis.

31
Q

Glucose-6-phosphatase deficiency

A

Glucose-6-phosphatase deficiency is the underlying cause of von Gierke disease (type a), which typically manifests with failure to thrive, lethargy, hepatomegaly, severe fasting hypoglycemia (causing hypoglycemic seizures), hyperlipidemia, and lactic acidosis.

Further characteristic findings include hyperuricemia and facial fat deposition (sometimes referred to as a “doll-like” face). Like other GSDs, von Gierke disease can be managed effectively with diet modifications (e.g., uncooked corn starch, glucose preparations), which aim to prevent hypoglycemia and muscle symptoms.

32
Q

Production of propionyl-CoA from protein degradation

Diagram

A
33
Q

Production of methylmalonyl-CoA from the degradation of branched chain AA’s and/or odd-chain fatty acids

Diagram

A
34
Q

First-line Tx of Lesch Nyen hyperurecemia

A

Drugs that inhibit the conversion of both hypoxanthine to xanthine and xanthine to urate:

First-line: xanthine-oxidase inhibitor (allopurinol)

35
Q

Fasting hypoglycemia with ketosis indicates what type of metabolic disorder?

A

Metabolic error of the liver in producing glucose during the fasting state

Hypoketotic hypoglycemia can be due to a fatty acid metabolic disorder (i.e. carnitine deficiency, MCAD deficiency)

Or debrancing enzyme deficiency (Cori disease)

36
Q

How does consuming alcohol when glycogen stores are low cause hypoglycemia?

A

Alcohol depletes NAD+ which shunts oxaloacetate into malate - inhibits gluconeogenesis leading to hypoglycemia

37
Q

Sources of gluconeogenesis after 24 hrs. fasting

A
38
Q

CO2 producing steps of TCA cycle

A
39
Q

What catalyzes the final step of gluconeogenesis in the liver?

A

Glucose-6-phosphatase catalyzes the conversion of glucose-6-phosphate into glucose

40
Q

Rate-limiting enzyme in gluconeogenesis

A

Fructose 1,6 bisphosphatase 1

41
Q

Glucokinase regulatory protein (GKRP)

A

translocates glucokinase to the nucleus in the setting of low glucose - when glucose concentration rises glucokinase is released from GKRP and moves to the cytosol to participate in glycolysis

42
Q

Rate-limiting enzyme in glycolysis

A

PFK-1

43
Q

Von Gierke disease

A

Lack normal activity of the enzyme glucose-6-phosphatase

Liver cannot metabolize glycogen into glucose - causes hepatomegaly

Fasting hypoglycemia with ketosis and lactic acidosis occurs

Occurs approximately 3-6 months of age many other inborn metabolic error present int he first few days of life

44
Q

What is the hallmark of beta-oxidation disorder?

A

Hypoketotic hypoglycemia

45
Q
A

M1 (53 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions