Metabolism and Nutrition Course
I.
II.
General Topics
A.
Diabetes/metabolism
B.
Inherited metabolic disorders
C.
Thyroid diseases
D.
Cortisol/stress
E.
Growth
F.
Nutrition
Teaching faculty
Mary Zoe Baker - endocrine physiology and pathophysiology
Paul Weigel – carbohydrate metabolism
Ann Louise Olson – lipid metabolism
Karla Rogers – protein metabolism
Brian Fuller - steroid hormone biochemistry and steroid receptor biochemistry
Alan Knehans - nutrition
John Holiman - endocrine pathology
Alan Weichman - endocrine histology
Jody Rada - embryology and endocrine systems
1
III.
Behavioral Objectives
A.
Carbohydrate biochemistry
Lecture 1
a.
Understand how two of the major sugars in our diet, fructose and
galactose, are activates (by phosphorylation) and enter glycolysis
b.
Know the genetic basis for lactose intolerance
c.
Know the genetic basis for classical galactosemia
d.
Be able to explain why hereditary fructose intolerance is more
serious than essential fructosuria. Which enzymes are involved in
each disease?
Lecture 2
a.
Be able to explain how glycogen synthesis and degradation are
simultaneously regulated in the same cell.
b.
Know how glycogen breakdown differs in muscle and liver
c.
Understand the concepts of coordinate control and cascade
amplification.
d.
Understand how the second messenger cAMP is turned on and
produced, how it signals within the cell and how the signal is shut
off.
e.
Know the process (including enzyme names) by which Glc or
Glc-1-P are released from glycogen.
Lecture 3
a.
Know th three glycolytic enzymes: hexokinase,
phosphofructokinese 1 and pyruvate kinase and how they regulate
the pathway
b.
Understand the 4 metabolic fates of pyruvate
c.
Be able to explain how the aerobic, anaerobic or alcohol
fermentation modes of the glycolytic pathway function and how
they differ.
d.
Understand how PFK-1 is regulated, how the regulator Fruc-2,6bisphosphate is made and how it affects glycolysis
e.
Be able to explain how and why the level of key enzymes in
glycolysis would be different between normal and diabetic patients
Lecture 4
a.
Know the 5 general mechanisms for controlling enzyme activity in
a metabolic pathway
b.
Be able to explain the concept of Dynamic State (macromolecular
turnover), Energy Charge and metabolic compartmentation
c.
Understand the 8 genera metabolic regulation principles (motifs).
2
Lecture 5
a.
Know the intermediates and enzymes of the citric acid cycle that
yield energy as reducing equivalents.
b.
Understand how the pyruvate and -ketoglutarate dehydrogenase
complexes are similar.
c.
Understand why humans cannot make proteins or carbohydrates
from 2-carbon acetyl-CoA molecules
d.
Be able to explain how the CAC is involved in both the
biosynthesis and the degradation of macromolecules.
Lecture 6
a.
Be able to explain the chemiosmotic hypothesis and how the
energy released during electron transport is utilized to make ATP
b.
Know the components of the electron transport chain and in their
order.
c.
Understand the standard oxidation-reduction potentials
d.
Understand the basic features of mitochondrial diseases
e.
Be able to explain how cytoplasmic-mitochondrial NADH shuttles
operate and why they are important.
Lecture 7
a.
Know the 4 gluconeogenic enzymes and their intermediates
b.
Be able to explain the coordinate control of glycolysis and
gluconeogenesis and how four major gluconeognic precursors
enter the pathway.
c.
Be able to explain the imbalance that occurs in intermediary
methabolic pathways during uncontrolled diabetes.
d.
Understand the role of mitochondrial and cytoplasmic
compartmentalization and the role of Acetyl-CoA in initiating
gluconeogenesis.
e.
Understand the Cori Cycle and how ethanol consumption affects
gluconeogenesis.
f.
Understand the biogenergetic explanation for why gluconeogenesis
is NOT a reversal of glycolysis and how much energy (e.g. ATP
and NADH) is needed to convert two pyruvates into one glucose.
Lecture 8
a.
Understand the 6 steps by which glucose-1-phosphate is converted
into glycogen.
b.
Know the coordinate control mechanisms that regulate both
glycogen synthesis and degradation.
Lecture 9
a.
Understand how the pentose phosphate (hexose monophosphate)
pathway ties together with the pathways of glycolysis, fatty acid
biosynthesis and nucleic acid synthesis.
3
b.
c.
d.
B.
Lipid Biochemistry
a.
b.
c.
d.
e.
f.
C.
Be able to explain how NADPH produced by the HMP pathway is
used for specialized purposes in erythrocytes and macrophages for
detoxification.
Understand the role of transketolase and transaldolase in
rearranging sugar carbon skeletons to interconvert 5-carbon sugars
with the two glycolytic intermediates, glyceraldehyde 3-phosphate
and fructose 6-phosphate.
Understand the basis for hemolytic anemias caused by glucose 6phosphate deficiencies and how a gene defect like this can also
confer a health benefit (and increased longevity) to patients.
Understand the composition of dietary lipids and the mechanisms the body
uses to digest dietary lipids.
Understand the mechanisms for transporting both dietary and
endogenously synthesized lipids in plasma.
Understand the interrelationships between lipoproteins in the plasma and
the means by which lipids are cleared from the plasma.
Understand the differences in fat metabolism in liver, adipose, muscle and
extrahepatic tissues in both the fed and fasted state.
Understand the physiologic basis for maintenance of body weight.
Understand the relationship between plasmid lipoproteins and
development of atherosclerosis and coronary heart disease.
Protein Biochemistry
1. Know 2 major mechanisms of nitrogen removal from amino acids.
2. Know enzymes involved in the urea cycle, the regulation and diseases of the
urea cycle.
3. Know the catabolism of the carbon skeletons of amino acids and diseases
associated with catabolism of amino acids.
4. Know the five different precursors that lead to the synthesis of the 10
nonessential amino acids.
5. Understand the systems involved in transfer of one-carbon units including 1)
tetrahydrofolaye and 2) S-adenosylmethionine
6. Know the pathways for the neurotransmitters synthesized from tyrosine,
tryptophan and glutamic acid
D.
Nutrition
1. Understand the dietary guidelines for Americans including the Food Guide
Pyramid and the FDA Food/Nutrition Board of Recommendations
2. Understand the Role of Nutrition in Aging
3. Know the risk of poor nutrition in the elderly
4
4. Know diseases in elderly related to nutrition and nutritional deficiencies in the
elderly
5. Know the use and regulations associated with herbals in the U.S.
6. Know the most commonly used herbals and the potentially toxic herbals
7. Know the effects of alcoholism and alcohol abuse on nutrition
8. Understand the concept of Nutrition Density
9. Understand the concept of Glycemic Index and know the factors that affect
Glycemic Index
10. Know types and sources and effects of dietary fiber
11. Understand the role of dietary lipids in cardiovascular disease
12. Understand the roles of vitamins as co-enzyme factors
13. Understand the roles of vitamins and minerals as antioxidants
14. Know the definition and prevalence of obesity and overweight
15. Know the determinants of overweight and obesity
16. Know therapies for overweight and obesity
F.
Physiology
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
Know the chemical class for each hormone.
List the three layers of the adrenal cortex, and know what steroid hormones are
synthesized by each layer.
Know how hormones are transported in the blood, know which hormones are
bound to proteins and know how protein binding affects hormone action.
Know the types of hormone receptors and know which hormones bind to each
type of receptor.
Know the anatomy of the hypothalamic-pituitary axis.
Know what hormones are secreted by the hypothalamus, anterior pituitary and
posterior pituitary.
Know how the steps of hormone release from the hypothalamus, anterior pituitary
and endocrine glands.
Know how the release each hormone from anterior pituitary is regulated through
negative feedback loops.
Know the 4 mechanisms of endocrine disorders.
List effects of insulin on glucose, protein and lipid metabolism in liver, muscle
and adipose tissue.
Describe the mechanism by which glucose levels regulate insulin secretion.
Describe how amino acids, GI peptides, the parasympathetic and sympathetic
nervous systems regulate insulin secretion.
List the effects of glucagon on metabolism and know the target organ.
Describe the regulation of glucagon release.
List the effects of the sympathetic nervous system on metabolism.
Know the effects of normal levels of cortisol on metabolism.
Describe the metabolic events that occur during fasting and the effects of
regulatory hormones.
Know mechanisms and effects of hypoglycemia.
Know mechanisms of Type 1 and Type 2 diabetes mellitus.
5
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
G.
List symptoms of Type 1 diabetes mellitus and know their mechanisms.
List symptoms of Type 2 diabetes mellitus.
List effects of chronic elevated glucose levels.
List factors that influence metabolic rate.
List the actions of thyroid hormone.
List steps involved in the synthesis and release of thyroid hormone.
Describe the cellular mechanism and regulation of thyroid hormone.
List symptoms of hyperthyroidism (Grave’s disease) and hypothyroidism
(Hashimoto’s disease) and understand the causes of the diseases.
Describe the effects of hyperthyroidism and hypothyroidism on negative feedback
systems regulating thyroid hormone release.
List steps in stressed-induced cortisol release.
List other chemicals that cause cortisol release.
List metabolic effects of cortisol for both basal levels and increased levels during
stress.
List metabolic effects of the stress-induced stimulation of the sympathetic nervous
system.
List mechanisms for hypercortisolism (Cushing’s disease) and hypocortisolism
(Addison’s disease) and know the effects of these diseases on the regulation of the
hypothalamus-pituitary-adrenal (HPA) axis.
List factors that affects growth.
List effects and mechanisms of growth hormone on growth.
Describe the regulation of growth hormone release.
List effects of IGF-1 on growth.
List other hormones that affect growth and know what effects they have on
growth.
Pathology
1.
2.
3.
4.
5.
6.
7.
8.
Define and use in the proper context
Discuss the similarities and differences between steroid hormones and
polypeptide hormones in terms of structure, function, mechanisms of
action
Describe the embryologic origin and development of the pituitary gland
Discuss the role of the hypothalamus on pituitary function
Name the major hormones of the anterior and posterior pituitary and
discuss their normal physiologic function
Categorize the cell types found within the anterior pituitary and their
secretory products
Discuss the regulatory mechanisms in place regarding the controlled
release of each of the pituitary hormones
Name the commonly encountered pituitary neoplasms, describe potential
related clinical signs and symptoms, and discuss the potential effects on
pituitary function
6
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
List the major endocrine disorders resulting from pituitary hyperactivity
and describe their etiology, clinical signs and symptoms, expected
laboratory findings, natural history, and methods used for diagnosis
List the major endocrine disorders resulting from pituitary hypoactivity
and describe their etiology, clinical signs and symptoms, expected
laboratory findings, natural history, and methods used for diagnosis
Describe the embryologic origin and development of the thyroid gland
List and describe the normal physiologic function of thyroid hormones
Discuss the regulatory controls on thyroid function
Describe the clinical features and expected laboratory findings in patients
with hyperthyroidism and hypothyroidism
Describe the differences in the microscopic appearance of the thyroid at
rest and during periods of heightened activity
Distinguish primary hyperthyroidism from secondary hyperthyroidism by
the appropriate use of laboratory testing
Compare and contrast Dequervain thyroiditis, lymphocytic thyroiditis, and
Riedel thyroiditis in terms of etiology, histologic appearance of the
thyroid, clinical signs and symptoms, and natural history
Discuss the similarities and differences between Graves disease and
Hashimoto thyroiditis in terms of predisposing factors, etiology and
pathogenesis, gross and microscopic appearance, clinical signs and
symptoms, and expected laboratory values
Discuss the potential clinical consequences of thyromegaly
Discuss the similarities and differences between papillary adenocarcinoma,
follicular adenocarcinoma, and medullary carcinoma of the thyroid in terms of
predisposing factors, progenitor cell type, gross and microscopic appearance,
clinical signs and symptoms, and natural history
Outline a diagnostic plan to evaluate a patient presenting with a solitary thyroid
nodule
Describe the embryologic origin and development of the parathyroid glands
Describe the normal physiologic function of parathyroid hormone
Discuss the regulatory controls on parathyroid gland function
Discuss the predisposing factors and describe the clinical features of patients with
hyperparathyroidism and hypoparathyroidism
Compare and contrast primary, secondary, and tertiary hyperparathyroidism in
terms of etiology, clinical signs and symptoms, and expected laboratory and
radiologic findings.
Discuss the similarities and differences between osteomalacia and osteoporosis in
terms of predisposing factors, etiology and pathogenesis, gross and microscopic
appearance of bone, clinical signs and symptoms, expected laboratory/radiologic
findings, and natural history
Outline a diagnostic plan to evaluate a patient presenting with asymptomatic
hypercalcemia
Describe the embryologic origin and development of the adrenal glands
7
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
H.
Discuss the histologic structure of the adrenal cortex and correlate that with the
class of hormone each produces.
List the major adrenal cortical hormones and the major adrenal medullary
hormones and describe the normal physiologic function of each
Discuss the regulatory controls on adrenal cortical function
Name the endocrine disorders that result from over secretion of adrenal cortical
hormones and discuss each in terms of etiology, clinical signs and symptoms,
expected laboratory/radiologic findings, and natural history
In patients with hyperadrenalism, discuss methods to distinguish between primary
and secondary causes.
Discuss the similarities and differences between patients with acute adrenocortical
insufficiency and patients with chronic adrenocortical insufficiency in terms of
clinical
signs
and
symptoms,
underlying
etiologies,
expected
laboratory/radiologic findings, and clinical course
In patients with hypoadrenalism, discuss methods to distinguish between primary
and secondary causes
List the major primary neoplasms of the adrenal and discuss the progenitor cell
type, gross and microscopic appearance, and potential clinical significance of
each
List the hormones produced by the pancreas and discuss the normal physiologic
action of each
Discuss the similarities and differences between patients with Type I diabetes
mellitus and Type II diabetes mellitus in terms of predisposing factors, etiology
and pathogenesis, microscopic appearance, clinical signs and symptoms, expected
laboratory findings, natural history, and potential complications
Discuss the clinical significance of gestational diabetes on both the mother and
the fetus
List the major Aendocrine@ neoplasms of the pancreas, and discuss the progenitor
cell type, gross and microscopic appearance, and potential clinical significance of
each
Name the major neoplasms arising from the adrenal medulla and discuss each in
terms of clinical signs and symptoms, expected laboratory findings, natural
history, and potential complications
Describe the major classification of the Multiple Endocrine Neoplasia Syndromes
and compare and contrast the disorders in terms of clinical signs and symptoms,
expected laboratory findings, natural history, and potential complication
Pharmacology
Adrenal Gland Disorders
Describe the roles of the various zones of the adrenal cortex in hormone synthesis.
Explain the regulation of glucocorticoid, adrenal androgen, and mineralocorticoid
secretion.
Compare and contrast therapeutic regimens for treatment of Cushing's syndrome, based
on the etiology of the disease in a particular patient.
8
Discuss the methods of, and rationale behind, steroid replacement in the treatment of
adrenal adenoma.
Explain the difference between primary and secondary aldosteronism.
Discuss some of the potential side effects of systemic glucocorticoid use, and how the
risk of developing these side effects may be minimized.
Recommend appropriate counseling points for a patient initiating long-term
glucocorticoid therapy.
Diabetes:
Know the sites and cellular physiology of insulin action.
Know the regulation of insulin processing, secretion and degradation.
Understand therapeutic goal of Type I diabetes how to use the drugs to treat it.
Know the different delivery methods for insulin and the side effects associated with them.
Understand therapeutic goal of Type II diabetes and how to use the drugs to treat it.
Know the factors to consider in the treatment of diabetic patients and how to compensate
for those factors.
Know what glucagon is, its sites of action, and its clinical uses.
Thyroid Disorders
Identify hyper- or hypothyroidism given a set of laboratory results.
Differentiate between hyper- and hypothyroidism based on signs and symptoms.
Identify adverse effects of treatment modalities for hyper- and hypothyroidism.
Compare and contrast the products available for thyroid supplementation in
hypothyroidism, and describe the drug of choice.
Hyperlipidemia
Describe the prevalence of lipid abnormalities (total cholesterol, low-density
lipoprotein cholesterol [LDL], and high-density lipoprotein cholesterol [HDL]) in the
United States and trends in lipid concentrations over time and among various racial
groups.
Describe how dietary fat and endogenous lipoprotein metabolism are interrelated and the
major metabolic pathways for lipoprotein and apolipoprotein synthesis and catabolism.
Outline the pathogenesis of atherosclerotic plaque formation, focusing on the roles of
adhesion molecules, cytokines, LDL, oxidized LDL, HDL, and the triglyceride-rich
particles very low-density lipoprotein (VLDL).
List the major lipoprotein disorders associated with ab
Outline the components of appropriate therapeutic lifestyle changes.
Describe the role of lipoprotein analysis in the initial evaluation and long-term
management of patients with lipid disorders, and list the major modifiable and
nonmodifiable risk factors for coronary heart disease (CHD).
Describe the mechanism of action, effects on lipids and lipoproteins, starting and
maintenance doses, adverse effects, drug interactions, and relative costs of bile acid
resins, fibric acid derivatives, niacin, ezetimibe, and statins.
Match the lipid-lowering drugs with specific lipid disorders such as
hypercholesterolemia, combined hyperlipidemia, and hypertriglyceridemia to maximize
the changes in lipids and lipoproteins.
9
Describe when combination pharmacotherapy for hyperlipidemia is most appropriate.
10