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T1 - Integrated (Full Review) > Biochemistry - Gastrointestinal Block > Flashcards

Biochemistry - Gastrointestinal Block Flashcards

1
Q

Describe the very general conditions of metabolism in the well-fed state (i.e. state of nutrients in the gut and blood, organs involved, processes involved, hormones involved, etc.).

A
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2
Q

Describe the very general conditions of metabolism in the fasting state (i.e. state of nutrients in the gut and blood, organs involved, processes involved, hormones involved, etc.).

A
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3
Q

Name a few metabolic processes activated in the well-fed state.

A

Glycogenesis;

protein synthesis;

fatty acid synthesis;

triacylglycerol synthesis;

VLDL synthesis

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4
Q

Name a few metabolic processes activated in the fasting state.

A

Gluconeogenesis;

ketogenesis;

triacylglycerol hydrolysis;

glycogenolysis;

protein catabolism

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5
Q

Which protein is useful for cleaving lipids to enter adipocytes when in the well-fed state?

Which protein is useful for cleaving lipids to exit adipocytes when in the fasting state?

A

Lipoprotein lipase;

hormone-sensitive lipase

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6
Q

What is the main metabolic hormone of the well-fed state?

What are the main hormones of the fasting state?

A

Insulin;

glucagon, epinephrine

(also cortisol and growth hormone)

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7
Q

The metabolic goal of the fasting state is to increase plasma levels of what two substances?

A

Glucose;

ketones

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8
Q

What is insulin’s main role at adipose and skeletal muscle tissues?

A

To increase the amount of GLUT4 in the cell membranes

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9
Q

Name some of the transporters and enzymes whose activity/expression is increased by insulin.

A

GLUT4

Glucokinase

PFK-1 (via PFK-2)

Glycogen synthase

PDC

Acetyl-CoA carboxylase

Lipoprotein lipase

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10
Q

Is insulin generally responsible for phosphorylation or dephosphorylation of metabolic enzymes?

A

Dephosphorylation (via protein phosphatase 1)

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11
Q

What is the immediate product of acetyl-CoA carboxylase?

What effect does it have on β-oxidation? How?

A

Malonyl-CoA;

decreased –> via inhibition of CAT1

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12
Q

Name some of the transporters and enzymes whose activity/expression is increased by glucagon.

A

Glycogen phosphorylase

FBPase-2

PEP carboxykinase

Hormone-sensitive lipase

Perilipin

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13
Q

Is glucagon generally responsible for phosphorylation or dephosphorylation of metabolic enzymes?

A

Phosphorylation (via protein kinase A)

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14
Q

Insulin indirectly dephosphorylates metabolic enzymes by activating:

Glucagon indirectly phosphorylates metabolic enzymes by activating:

A

Protein phosphatase 1

Protein kinase A

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15
Q

Describe the respective effects of insulin and glucagon on F2,6BP.

A
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16
Q

Does glucagon activate or inhibit pyruvate kinase?

A

Inhibit

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17
Q

In the well-fed state, lipoprotein lipase expression is elevated in what tissue(s)?

A

Adipose

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18
Q

In the fasting state, lipoprotein lipase expression is elevated in what tissue(s)?

A

Muscle

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19
Q

What effect does xyulose 5-phosphate have on the PFK-2/FBPase-2 bifunctional enzyme?

A

Activating PFK-2

(similarly to insulin, X5P activates a phosphatase)

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20
Q

Glucose 6-phosphate dehydrogenase is inactivated by:

A

NADPH

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21
Q

What two processes account for hepatic ethanol metabolism?

A
  1. Redox NADH and acetate production (basic steps in cytosol and mitochondria involving alcohol dehydrogenase and acetaldehyde dehydrogenase)
  2. The microsomal EtOH oxidizing system (hepatic SER)
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22
Q

Describe the two main reactions of basic ethanol metabolism.

Where do they occur in the cells?

A
  1. Cytosol: alcohol dehydrogenase turns EtOH into acetaldehyde (converting NAD+ –> NADH)
  2. Mitochondria: acetaldehyde dehydrogenase turns acetaldehyde into acetate
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23
Q

What are the two enzymes of basic alcohol metabolism?

(Where do the reactions take place?)

A

Alcohol dehydrogenase (cytosol);

alcetaldehyde dehydrogenase (mitochondria)

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24
Q

Name the intermediate and final product of basic ethanol metabolism.

A

EtOH –> Acetaldehyde –> Acetate

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25
Q

The final product of basic ethanol metabolism is __________.

What happens to this product next?

A

Acetate;

it enters the bloodstream and is turned into acetyl-CoA in extrahepatic tissues

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26
Q

Which of the two basic ethanol metabolism steps produces NAD+?

Which of the two basic ethanol metabolism steps produces NADH?

A

Neither;

both

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27
Q

For every one molecule of EtOH metabolized, ___ NADH are produced.

A

2

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28
Q

What is the basic explanation for the effects of alcohol on body metabolism?

A

The buildup of NADH leads to a depletion of NAD+ that is needed for the CAC and many other reactions

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29
Q

What change in the NAD+:NADH ratio occurs during alcohol use?

A

A decrease

(insufficient NAD+ for body reactions)

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30
Q

True/False.

Most basic EtOH metabolism occurs via the microsomal EtOH oxidizing system in the hepatic ER.

A

False.

This is only induced when EtOH levels are high and, even then, only accounts for 10 - 20% of EtOH converted to acetaldehyde.

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31
Q

When is the microsomal EtOH oxidizing system active?

A

It is induced/increased in expression by high levels of EtOH

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32
Q

Which form of alcohol metabolism is present at baseline, low levels of EtOH?

A

The alcohol dehydrogenase / acetaldehyde dehydrogenase system

(the microsomal EtOH oxidizing system is only active/induced when EtOH levels are high)

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33
Q

What is cytochrome P450?

In what tissue(s)/organelle(s) is it found in high concentrations?

A

A mixed-function oxidase;

hepatic ER

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34
Q

What are the substrates and products of the microsomal ethanol oxidizing system?

A

Substrates: EtOH, NADPH (+ H+ + O2)

Products: Acetaldehyde, NADP+ (+ 2 H2O)

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35
Q

What enzyme is responsible for the microsomal ethanol oxidizing system?

Where does it take place?

A

Cytochrome P450;

the hepatic ER

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36
Q

What hepatic function is increased by chronic EtOH use?

How much?

A

Cytochrome P450 (CYP2E1);

an induced 5- to 10-fold increase

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37
Q

What electron carrier is involved as a substrate of basic hepatic EtOH metabolism?

What electron carrier is involved as a substrate of the microsomal ethanol oxidizing system?

A

NAD+;

NADPH

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38
Q

What product of EtOH metabolism is most responsible for liver damage in chronic alcoholism?

A

Acetaldehyde

(produced by the microsomal EtOH oxidizing system)

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39
Q

What hepatic enzyme produces acetaldehyde from ethanol in the cytosol?

What hepatic enzyme produces acetaldehyde from ethanol in the endoplasmic reticulum?

What hepatic enzyme produces acetate from acetaldehyde in the mitochondria?

A

Alcohol dehydrogenase;

cytochrome P450 (of the MEOS);

acetaldehyde dehydrogenase

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40
Q

What hepatic enzyme produces acetaldehyde from ethanol in the cytosol?

A

Alcohol dehydrogenase

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41
Q

What hepatic enzyme produces acetaldehyde from ethanol in the endoplasmic reticulum?

A

Cytochrome P450 (of the MEOS)

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42
Q

What hepatic enzyme produces acetate from acetaldehyde in the mitochondria?

A

Acetaldehyde dehydrogenase

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43
Q

What are the three main damaging effects of cytochrome P450 induction by chronic alcoholism?

A

1. [Acetaldehyde] increase

2. [Free-radical oxygen species] increase

3. P450 now less available for drug/xenobiotic metabolism (may result in toxic drug levels)

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44
Q

Describe the respective issue with each of the following three polymorphisms involving enzymes of EtOH metabolism:

ADH1*B1 (alcohol dehydrogenase)

A

Underactive isoform

  • (homozygotes are at increased risk for Wernicke-Korsakoff;*
  • increased EtOH leads to decreased thiamine uptake in the gut)*
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45
Q

Describe the respective issue with each of the following three polymorphisms involving enzymes of EtOH metabolism:

ADH1*B2 (alcohol dehydrogenase)

A

Overactive isoform

(acetaldehyde production > acetate production –> acetaldehyde builds up)

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46
Q

Describe the respective issue with each of the following three polymorphisms involving enzymes of EtOH metabolism:

ALDH2 (acetaldehyde dehydrogenase)

A

Underactive isoform

(Km increases –> acetaldehyde builds up;

patient has severe sensitivity to alcohol –> nausea and vomiting)

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47
Q

What drug blocks acetaldehyde dehydrogenase and causes nausea and vomiting in those that drink EtOH?

Why these symptoms?

A

Disulfiram (antabuse);

acetaldehyde buildup

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48
Q

Which has a lower Km for ethanol, alcohol dehydrogenase or CYP2E1 (cytochrome P450 of the MEOS)?

So, which is more active in interacting with EtOH?

A

Alcohol dehydrogenase;

alcohol dehydrogenase

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49
Q

What are some risk factors for thiamine deficiency?

A

Alcoholism (poor diet; lack of magnesium)

ADH1*B1 mutation (buildup of EtOH decreases thiamine uptake in gut)

Hepatic damage (decreases thiamine pyrophosphate formation)

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50
Q

What are some neurological S/Sy of Wernicke-Korsakoff?

A

Amnestic disorder,

cognitive impairment,

ophthalmoplegia,

abnormal stance/gait

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51
Q

A 46-year-old female complains of loss of appetite, fatigue, muscle weakness, and emotional depression. She has had occasional pain in the area of her liver, at times accompanied by nausea and vomiting.

Recently fired for absenteeism. Divorced 10 months earlier.

Physical exam: Patient appears disheveled and pale. Tenderness to light percussion over liver and detectable small amount of ascites fluid within peritoneal cavity. Lower edge of her liver is palpable, appears enlarged, and it feels more firm and nodular than normal. Suggestion of mild jaundice.

No obvious neurologic or cognitive abnormalities are present.

Hint of alcohol on patient’s breath, patient admits drinking gin on a daily basis (4 to 5 drinks, or 68 to 85 g ethanol) and eating infrequently for last 5 or 6 years.

What tests might you run?

A

Serum alcohol level

Serum ALT and AST

Serum ALP

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52
Q

What is considered ‘moderate drinking’?

A

Men: 2 drinks / day

Women: 1 drink / day

1 drink = EITHER 12 oz. of regular beer, 5 oz. of wine, OR 1.5 oz. distilled spirits (80-proof)

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53
Q

For the purposes of defining moderate drinking, men are limited to ≤ 2 drinks / day and women to ≤ 1 drink / day.

What is the definition of ‘one drink’?

A

One drink is ONE of the following:

12 oz. of regular beer,

5 oz. of wine,

1.5 oz. distilled spirits (80-proof)

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54
Q

What quantity of beer is considered ‘one drink’?

What quantity of wine is considered ‘one drink’?

What quantity of spirits (80-proof) is considered ‘one drink’?

A

12 oz.

5 oz.

1.5 oz.

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55
Q

What enzyme category in particular is inhibited by the increase in the NADH:NAD+ ratio that alcohol ingestion causes?

What is the major result?

A

Dehydrogenases;

inhibition of glycolysis, the CAC, and β-oxidation

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56
Q

What results happen after a person ingests alcohol and dehydrogenases are shut down by the increased NADH:NAD+ ratio (leading to inhibition of glycolysis, the CAC, and β-oxidation)?

A

Lactic acidosis

Hyperuricemia (lactate competes with urate for excretion)

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57
Q

Does alcohol abuse typically cause hyperglycemia or hypoglycemia?

A

Hypoglycemia

(poor diet + inhibited use of gluconeogenic amino acids)

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58
Q

What effect does alcohol abuse have on serum lipid levels?

A

Increased synthesis of triglycerides, VLDLs, and ketone bodies

–> hyperlipidemia and hepatic steatosis

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59
Q

What effect does alcohol abuse have on drug metabolism?

A

Decreased capacity

(increased risk of overdose because P450 is occupied metabolizing the EtOH)

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60
Q

Name some of the generic outcomes of alcohol abuse on glucose levels, lipid levels, and other metabolites.

A

Hypoglycemia

Hyperlipidemia

Hyperuricemia

Lactic acidemia

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61
Q

What causes hangovers?

A

Acetaldehyde and ROS buildup and subsequent cellular toxicity

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62
Q

How does acetaldehyde damage cells?

What are some specific examples?

A

By binding amino acids and proteins

  • Impairs microtubules (decreases vesicle secretion)
  • Impairs glutathione (ROS increase)
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63
Q

What immediate non-metabolic effect does alcohol-induced damage of mitochondria by free radicals have on the cell?

A

A further increase in [acetaldehyde] and [ROS]

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64
Q

What are the stages of hepatic damage?

A
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65
Q

Describe some of the effects of decreased liver function due to severe hepatic disease.

A

Loss of albumin –> ascites

Loss of coagulation factors –> increased PTT

Loss of VLDL synthesis and gluconeogenesis –> hypoglycemia

Lack of glutathione –> hemolytic anemia

Decreased bilirubin conjugation, bile acid synthesis, ammonia excretion –> jaundice and hyperammonemia

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66
Q

ALT and AST are 10x their normal values.

What do you suspect?

A

Acute viral hepatitis

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67
Q

ALT and AST are increased but <4x their normal values.

What do you suspect?

A

Chronic alcohol-hepatitis

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68
Q

ALT and AST are increased but <4x their normal values.

What do you suspect?

ALT and AST are >10x their normal values.

What do you suspect?

A

Chronic alcohol-hepatitis

Acute viral hepatitis

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69
Q

A decreased BUN indicates:

An increased BUN indicates:

A

Liver dysfunction;

renal dysfunction

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70
Q

Serum γ-glutamyl transferase is elevated. What does this indicate?

Serum total bilirubin is elevated. What does this indicate?

A

Liver disease;

liver disease (non-specific)

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71
Q

PTT elevation can be caused by dysfunction of what GI organ?

A

The liver

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72
Q

Decreased total serum protein or serum albumin indicate an issue with what organ system(s)?

A

Liver or kidneys

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73
Q

An increase in alkaline phosphatase (ALP) indicates an issue with which organ(s)?

A

Liver or bone

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74
Q

True/False.

Elevated ALT and creatinine can be indicators for cardiac damage, not just liver dysfunction.

A

False.

Elevated AST and creatinine can be indicators for cardiac damage, not just liver dysfunction.

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75
Q

An individual presents with elevated serum alkaline phosphatase and a normal serum γ-glutamyl transferase.

What is the likely organ system involved?

A

Bone

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76
Q

A patient presents with an ALT/AST ratio >1.

What do you suspect?

A

Acute viral hepatitis

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77
Q

A patient presents with an ALT/AST ratio <1.

What do you suspect?

A

Chronic alcohol-hepatitis

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78
Q

What is the normal ALT/AST ratio?

A

1

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79
Q

Why might serum folate, vitamin B12, and iron levels be slightly depressed in an alcoholic?

A

Poor nutrition

(vitamin B12 and iron are also dependent on the liver for their carrier proteins)

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80
Q

What steps should an alcoholic be encouraged to take?

A

1. Abstain from alcohol immediately

2. Improve nutritional status

3. Seek counseling from a drug and alcohol rehabilitation unit, for the appropriate psychological, social and supportive counseling.

4. Keep regular follow-up appointments to monitor liver function.

81
Q

Via what basic mechanism does alcohol use cause hypoglycemia?

A

By impairing gluconeogenesis

82
Q

What vitamin does EtOH competitively inhibit at retinol dehydrogenase?

What other effect does it have on this vitamin?

A

Vitamin A;

induction of MEOS, which may further increase vitamin A catabolism

83
Q

How is methanol metabolized by the body?

How would you treat a methanol poisoning?

A

It is converted to formaldehyde (then formic acid);

fomepizole (blocks alcohol dehydrogenase so the MeOH can be excreted in the urine without being turned into formaldehyde)

84
Q

How is ethylene glycol metabolized by the body?

How would you treat a methanol poisoning?

A

It is converted to three acids (glycolic acid, glyoxylic acid and oxalic acid), causing metabolic acidosis;

fomepizole (blocks alcohol dehydrogenase so the MeOH can be excreted in the urine)

85
Q

Fomepizole blocks what enzyme?

A

Alcohol dehydrogenase

86
Q

Of U.S. diabetics, what percentage are type I?

What percentage are type II?

A

5 - 10%

90 - 95%

87
Q

What ethnicity is most at-risk for type I diabetes mellitus?

What gender?

What age?

A

Caucasian > African-American, Hispanic >>> Asian;

men > women;

11 - 13 years of age

88
Q

What ethnicity is most at-risk for type II diabetes mellitus?

What gender?

What age?

A

Hispanic, Native American, African-American, Asian > caucasian;

men = women;

> 40

89
Q

Describe the development of type I diabetes mellitus in terms of cause, timing, and mechanism.

A

Viral infection induces an autoimmune attack on the pancreatic β-cells (molecular mimicry);

may take up to 10 years post-infection to become a clinical presentation

91
Q

How is type I diabetes mellitus diagnosed (ADA guidelines)?

(Hint: there are 4 potential tests.)

A

HbA1c ≥ 6.5%

FPG > 125 mg/dL

OGTT > 200 mg/dL (at 2 hours)

RPG > 200 mg/dL (with classic S/Sy)

92
Q

What are some of the common signs and symptoms of type I diabetes mellitus?

A

Polydipsia, polyphagia, polyuria;

unexplained weight loss, lassitude, muscle cramps, blurred vision, peripheral neuropathy, headaches, GI complications

93
Q

What values for the following tests would indicate prediabetes?

FPG

HbA1c

OGTT

A

FPG: 110 - 125 mg/dL

HbA1c: 5.6 - 6.4%

OGTT: 140 - 200 mg/dL

94
Q

What are the normal values for the following tests?

FPG

HbA1c

OGTT

A

FPG: 70 - 110 mg/dL

HbA1c: < 5.6%

OGTT: < 140 mg/dL

95
Q

To what conditions is a patient with prediabetes especially predisposed?

A

Type II diabetes mellitus;

macrovascular disease

96
Q

Describe the requirements for a patient to be diagnosed with metabolic syndrome.

(I.e. they must have ≥ ____ of which clinical test values?)

A

Must have ≥3 of the following:

Obesity

Elevated glucose levels (≥ 110 mg/dL FPG)

Dislipidemia (elevated TG and LDL, decreased HDL)

Hypertension

Insulin resistance

Prothrombotic state

Proinflammatory state

97
Q

To be diagnosed with metabolic syndrome, a patient must have ≥ 3 of what features?

A

Obesity

Elevated glucose levels (≥ 110 mg/dL FPG)

Dislipidemia (elevated TG and LDL, decreased HDL)

Hypertension

Insulin resistance

Prothrombotic state

Proinflammatory state

98
Q

Which are the two dominant factors in a patient with metabolic syndrome that especially predispose that individual to T2DM and vascular disease?

A

Abdominal obesity,

insulin resistance

99
Q

What happens to insulin levels in an individual as they develop T2DM?

A

An initial compensatory insulin increase;

a steady decrease in insulin production over decades

100
Q

Describe the changes in serum glucose and insulin in a patient as they develop T2DM.

A
101
Q

What percentage of patients with T2DM are obese?

A

90%

104
Q

What are the two features of T2DM development?

A

Peripheral insulin resistance

+

insufficient insulin-secretory (compensatory) mechanism

105
Q

What are some of the signs and symptoms of type II diabetes mellitus?

A

All the S/Sy of T1DM

+

slow-healing sores, itchy skin, frequent yeast infections

106
Q

Do pregnant women normally develop hyperglycemia or hypoglycemia during pregnancy?

When?

Why?

A

Hypoglycemia;

intraprandial / during sleep;

fetal glucose need

107
Q

Does intraprandial hypoglycemia increase or decrease as pregnancy progresses?

A

Increase

(fetal demand increases)

108
Q

In non-specific terms, why do some women develop gestational diabetes mellitus?

A

Susceptible women develop insulin resistance in response to placental steroid and peptide synthesis

109
Q

How does ethnicity affect a woman’s risk of gestational diabetes mellitus?

A
110
Q

A pregnant woman begins to develop insulin resistance in response to the increasing placental steroid and peptide hormone synthesis.

What will occur if her insulin levels are inadequate?

A

Recurrent postprandial hyperglycemia –>

accelerated fetal growth

111
Q

What are some of the effects of surging hyperglycemia and hyperinsulinemia (related to gestational diabetes mellitus) on the fetus?

A

Macrosomia, fetal hypoxia;

hypertension, cardiac remodeling/hypertrophy

112
Q

What are some of the risk factors for gestational diabetes mellitus?

Consider: age, ethnicity, weight, and medical history.

A

Age: > 35

Ethnicity: Hispanic, Native American, African-American, Asian > caucasian

Weight: Obesity

Medical History: obstetrical Hx of diabetes or macrosomia; family Hx of DM

114
Q

What percentage of women with gestational DM will develop overt DM within 5 years of delivery?

A

~33%

(higher risk ethnicities nearing 50%)

115
Q

How is gestational DM diagnosed?

When?

A

2 steps:

1-hour glucose challenge test (GCT)

2-hour OGTT;

between week 24 and 28

(week 13 for those with risk factors)

116
Q

What is the major acute complication of T1DM?

What is the major acute complication of T2DM?

A

Diabetic ketoacidosis (DKA);

hyper(HHNC)

117
Q

Which has a higher mortality rate, diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic non-ketotic coma (HHNC)?

A

HHNC

118
Q

True/False.

Both DKA and HHNC are characterized by hyperglycemia and dehydration.

A

True.

119
Q

What are some causes of DKA in a patient with T1DM?

A

New onset of DM,

insulin disruption,

infection

120
Q

What are some causes of HHNC in a patient with T2DM?

A

Secondary to DM effects:

infection,

fluid loss,

certain drugs

121
Q

What are the S/Sy of DKA?

A

1. Serum glucose > 300 mg/dL

2. Acidosis

3. Low HCO3- (< 15 mEq/L)

4. Ketonemia, ketonuria

5. Acetone breath

122
Q

What are the S/Sy of HHNC?

A

1. Serum glucose > 600 mg/dL

2. Hyperosmolarity > 320 mOsm/dL

3. Dehydration

4. Na+/K+ loss (via osmotic diuresis)

123
Q

How is DKA treated?

A

Fluids

+

Insulin (after 1st hour)

+

Dextrose (eventually, to prevent hypoglycemia)

124
Q

How is HHNC treated?

A

Similar to DKA (fluid –> insulin –> glucose)

+ careful electrolyte monitoring

125
Q

List some of the chronic complications of diabetes.

A

Neuropathies,

peripheral vascular disease

diabetic nephropathy,

cataracts, glaucoma, retinopathy,

CVD,

skin lesions

126
Q

Diabetics should be encouraged to aim for a HbA1c of:

A

< 7%

127
Q

What are the main sugar- and insulin-related goals of diabetes medication?

A

HbA1c < 7%

Postprandial glucose of 90 - 130 mg/dL

Increased insulin secretion

Decreased insulin resistance

128
Q

Why don’t T2 diabetics get DKA?

A

They have sufficient insulin secretion to prevent ketone production

129
Q

Other than meglitinides, thiazolidinediones, and incretins, name three categories of drugs often used to treat T2DM.

A

Biguanides (metformin)

Sulfonylureas (tolbutamide, glipizide, glyburide)

α-glucosidase (miglitol, acarbose) / SGLT-2 inhibitors (

130
Q

Other than biguanides, sulfonylureas, and α-glucosidase/SGLT inhibitors, name three categories of drugs used to treat T2DM.

A

Meglitinides (repaglinide)

Thiazolidinediones (rosiglitazone, pioglitazone)

Incretins (DDP-4 inhibitors; glucose-dependent insulinotropic peptide and GLP-1 analogs)

131
Q

What results occur with virtually all diabetic medications?

A

A decrease in FPG and a decrease in HbA1c

132
Q

Name three diabetic drug types that increase insulin secretion.

A

Sulfonylureas (long-acting);

meglitinides (short-acting);

incretins

133
Q

Name a diabetic drug type that decreases glucagon secretion.

A

Incretins

134
Q

Name two diabetic drug types that increase insulin sensitivity (in the liver, skeletal muscle, and adipose).

A

Biguanides (e.g. metformin);

glitazones

135
Q

Name a diabetic drug type that decreases glucose absorption in the gut.

Name a diabetic drug type that decreases glucose absorption in the kidneys.

A

α-glucosidase inhibitors;

SGLT inhibitors

136
Q

What is the basic mechanism by which metformin decreases FPG and HbA1c?

What is the basic mechanism by which meglitinides decrease FPG and HbA1c?

What is the basic mechanism by which α-glucosidase (or SGLT-2) inhibitors decrease FPG and HbA1c?

A

Increased insulin sensitivity;

increased insulin secretion;

decreased gut (or renal) glucose absorption

137
Q

What is the basic mechanism by which incretins decrease FPG and HbA1c?

What is the basic mechanism by which thiazolidinediones decrease FPG and HbA1c?

What is the basic mechanism by which sulfonylureas decrease FPG and HbA1c?

A

Increased insulin secretion / decreased glucagon secretion;

decreased renal glucose reabsorption;

increased insulin secretion

138
Q

Which is long-acting, sulfonylureas or meglitinides?

A

Sulfonylureas

139
Q

What is another term for glitazones?

A

Thiazolidinediones

140
Q

How do thiazolidinediones (glitazones) affect blood sugar?

A

PPAR-γ receptor activation –> release of adiponectin

–> increased insulin sensitivity

141
Q

How do sulfonylureas affect blood sugar?

A

They depolarize pancreatic β-cells by inhibiting KATP channels

(causing increased insulin secretion)

142
Q

What enzyme can digest sucrose? What are the products?

A

Sucrase — glucose + fructose

143
Q

What enzyme can digest trehalose? What are the products?

A

Trehalase — glucose

144
Q

What enzyme can digest lactose? What are the products?

A

Lactase — glucose + galactose

145
Q

What enzyme can digest α-1,6 glycosidic linkages in the gut? What is the product?

A

isomaltase (α-dextrinose) — glucose

146
Q

Why can infants absorb some oligosacharrides?

(Hint: it is the same reason they can absorb their mothers’ IgA without breaking them down.)

A

Leaky tight junctions

(not yet fully formed enterocyte connections)

147
Q

True/False.

Adults can only take up monosacharrides, but infants can take up oligosacharrides.

A

True.

(Due to infantile ‘leaky’ tight junctions)

148
Q

What is inulin?

A

A non-digestible fructose polymer

149
Q

What is sucralose?

A

(Splenda) A non-digestible sucrose that is chlorinated

150
Q

Which hexokinase cannot phosphorylate fructose to F6P?

A

Glucokinase (hexokinase IV)

151
Q

What monosacharrides can be phosphorylated by hexokinase I?

(Are there Km differences?)

A

Glucose, fructose

(lower Km for glucose)

152
Q

What two hepatic enzymes are the main factors controlling fructose metabolism?

A

Fructokinase,

aldolase B

153
Q

What happens to a fructose molecule after entering a hepatocyte?

A

Fructokinase converts it to F1P;

aldolase B then converts it to glyceraldehyde and DHAP

(then glyceraldehyde 3-P, a glycolytic intermediate)

154
Q

What happens if a person is deficient in fructokinase?

A

Fructosuria

(fructose is never converted to F1P, and so it accumulates in the urine)

155
Q

What happens if a person is deficient in aldolase B?

A

Essential fructosemia (hereditary fructose intolerance)

–> F1P builds up, inhibiting glycogen phosphorylase and damaging the liver

156
Q

What enzyme is deficient in essential fructosemia?

What enzyme is deficient in fructosuria?

A

Aldolase B;

fructokinase

157
Q

Name the respective buildup products for the following two diseases:

Fructosuria

Essential fructosemia

A

Fructose (in urine)

F1P (in liver)

158
Q

Which of the following damages the liver, fructosuria or essential fructosemia?

A

Essential fructosemia

159
Q

A parent brings their 3-year-old child into the clinic with complaints of vomiting, lethargy, irritability, and convulsions. The child has met all their milestones and been otherwise healthy. The S/Sy began recently when the child was first introduced to fruit juices.

What inborn error of metabolism comes to mind?

A

Essential fructosuria

160
Q

Will essential fructosuria cause hyperglycemia or hypoglycemia?

A

Hypoglycemia

(due to glycogen phosphorlyase inhibition by F1P)

161
Q

Patients with essential fructosuria are advised to avoid ingesting what sugar(s)?

A

Fructose,

sucrose,

sorbitol (converted to fructose via sorbitol dehydrogenase)

162
Q

What enzyme can interconvert glucose and sorbitol?

Where is it found?

A

Aldose reductase;

the lens, retina, and Schwann cells

(the cause of some diabetic complications)

163
Q

What is the purpose of pyrophosphorylases?

A

To activate monosacharrides by attaching UDP to them

164
Q

True/False.

UDP-galactose can be formed by transfering UDP from UDP-glucose to a Gal-1P.

A

True.

165
Q

What is galactosemia?

What enzyme(s) is(are) deficient?

A

Galactose buildup;

galactokinase OR galactose 1-phosphate uridyl transferase

166
Q

Which shows up right away at birth and is more severe,

galactosemia or essential fructosemia?

A

Galactosemia

167
Q

What are some of the S/Sy of galactosemia?

A

S/Sy begin shortly after birth;

mental retardation, liver disease, cataract formation

168
Q

What is the underlying mechanism that explains diabetic retinopathy, cataract formation, and peripheral vascular disease?

A

Sorbitol accumulation in the lens, retina, and Schwann cells

(via aldose reductase conversion of glucose to sorbitol)

169
Q

How is galactosemia managed?

A

Simple removal of galactose from the diet

170
Q

Expression of what lactation protein is upregulated by prolactin?

A

α-lactalbumin

171
Q

(The child did not improve with a switch to formula and eventually developed cataracts and liver damage.)

A

Galactosemia (check via blood test);

remove galactose and lactose from the diet

172
Q

What enzyme and modifying protein are responsible for lactose formation in the mammary glands?

What substance increases expression of the modifying protein?

A

Galactosyl transferase, α-lactalbumin;

prolactin

173
Q

Via what mechanism does prolactin affect lactose production in breast milk?

A

Upregulation of α-lactalbumin

(galactosyl transferase switches from glycoprotein synthesis to lactose synthesis)

174
Q

Why are many compounds synthesized in the body (or drugs metabolized in the body) attached to uronic acids?

A

To increase solubility

(and make for easier transport)

175
Q

If a patient with lactose intolerance ingests a substance containing only lactose, what effect will the substance have on their blood glucose levels?

A

No effect

(the lactose is not absorbed)

176
Q

Describe the basic structure of cholesterol.

A

4 rings + hydrocarbon tail

177
Q

How is cholic acid (a bile acid) modified from normal cholesterol (shown below)?

A

Addition of hydroxyl groups + a carboxyl group

178
Q

What portion of a bile acid is conjugated to glycine or taurine?

A

The carboxyl group

180
Q

What class of enzyme converts cholesterol into its derivatives such as bile acids, steroid hormones, and calcitriol?

A

Monooxygenases

(oxygenating cholesterol)

181
Q

What are some of the potential fates of hepatic cholesterol?

A
  • Synthesis of plasma membranes
  • Export to peripheral tissues via VLDL
  • Secretion as bile acids/salts
  • Synthesis of calcitriol or other steroid hormones
182
Q

What do hepatic monooxygenase enzymes do to cholesterol?

What cofactors are needed?

A

Add hydroxyl groups to them;

NADPH, O2

183
Q

The hepatic monooxygenase enzymes are part of what system?

What nomenclature can be used to indicate 7α-hydroxylase?

A

Cytochrome P450;

CYP7A1

186
Q

How is a bile acid turned into a bile salt?

A

Via conjugation of its carboxyl group with either glycine or taurine

188
Q

What is the most common bile acid?

Is it primary (liver-synthesized) or secondary (gut-modified)?

A

Cholic acid;

primary

189
Q

Describe the enterohepatic circulation of bile salts.

A
190
Q

What is the rate-limiting step of bile acid synthesis?

What provides negative feedback to this enzyme?

A

7α-hydroxylase;

cholic acid

191
Q

What are the two main bile acids?

Which is a triol (3x -OH) and a better detergent than the corresponding diol (2x -OH)?

A

Cholic acid, chenodeoxycholic acid;

cholic acid

192
Q

What percentage of bile acids are reabsorbed in the gut and recirculated into bile?

A

90%

193
Q

How does cholestyramine (a medication) lower plasma cholesterol?

What dietary substance has the same effect?

A

By sequestering gut bile acids and increasing their excretion

(more cholesterol then needed to resynthesize the bile acids);

dietary fiber

194
Q

What medication is here described: sequesters gut bile acids to increased their excretion.

What is the overall effect?

A

Cholestryamine;

decreased plasma cholesterol

195
Q

Which is a better emulsifer, bile acids or bile salts?

Which is secreted into the bile?

Which is more easily reabsorbed in the gut?

A

Bile salts;

bile salts;

bile salts

197
Q

How do the gut flora interact with bile acids/salts?

A

Via conversion of 1° acids/salts into 2° acids/salts (removal of the 7α-OH);

via deconjugation (removal of glycine or taurine)

198
Q

Which is more soluble and more easily reabsorbed in the gut, primary or secondary bile acids/salts?

A

Primary (conjugated + one more hydroxyl group)

200
Q

What term indicates gallstone formation due to bile salt deficiency?

A

Cholelithiasis

(more cholesterol than bile salts –> the cholesterol precipitates)

201
Q

Define cholelithiasis.

How is it treated (give surgical and non-surgical options)?

A

Gallstone formation (due to bile salt deficiency);

laparoscopic cholecystectomy,

oral chenodeoxycholic acid

202
Q

How does oral chenodeoxycholic acid treat gallstones?

How quick acting are its effects?

A

By substituting the missing bile salts –> emulsifies / dissolves the gallstone cholesterol back into bile;

takes months-to-years

203
Q

What are some conditions/situations that can decrease [bile salt] and increase risk of cholelithiasis?

A

Ileal disease,

biliary obstruction (enterohepatic circulation interrupted),

hepatic dysfunction,

fibrates

204
Q

What does CYP7A1 indicate?

What is CYP2E1?

A

Cytochrome P450 7α​-1 hydroxylase

(rate-limiting enzyme for bile acid synthesis);

cytochrome P450 2E1 (alcohol dehydrogenase)

205
Q

True/False.

In the absence of prolactin, α-lactalbumin is a galactosyl transferase for glycoprotein synthesis.

A

True.

(With prolactin, it begins lactose synthesis)

206
Q

A 12 year old patient comes in after fainting during a long boy scouts trip. History reveals that father’s brother has ‘some troubles with sugars’ and maternal grandmother had died young of liver failure. Physical examination shows liver tenderness and moderate hepatomegaly, while blood tests reveal low blood sugar. Urine does not contain any free sugars.

What tentative diagnosis do you give; what recommendations do you have for the family?

A

Fructosemia;

advise parents to keep fructose out of diet.

207
Q

Imagine 2 molecules of glucose, one from the blood stream and the other stored in glycogen.

Which molecule will have a higher net energy yield after completing glycolysis?

A

The glucose molecule mobilized from glycogen stores

(it is already phosphorylated)

208
Q

The typical patient has had T2DM for __-__ years at the time a first diagnosis is made.

A

4, 7

209
Q

How does EtOH abuse cause thiamine deficiencies?

A
  • Inadequate nutrition
  • Decreased enterocyte active transport
  • Decreased thiamine stores (hepatic steatosis / fibrosis)
  • Decreased Mg+ (required for thiamine utilization)

T1 - Integrated (Full Review) (29 decks)

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