Снимок новаторского подхода к комплексному преподаванию медицинской биохимии в рамках учебной программы для оценки результатов.

Introduction

The educational challenge

Teaching and learning experiences in medical biochemistry (MB), one of the
primary basic science subjects taught in the early pre-clerkship curriculum in
U.S. medical schools, pose equal challenges for both medical students and
educators. From the student’s perspective, the subject is cognitively
demanding due to its voluminous content, long, winding pathways, and
multifaceted metabolic cycles. Thus, unable to purposefully comprehend or
appreciate its relevance to future medical practice, newly admitted medical
students develop a negative bias towards the subject. As a solution, students
habitually commit to rote memorization of the associated concepts to pass
internal assessments and medical board exams. Consequently, by the time
MB’s relevance approaches clarity during clinical years,
self-recapping/relearning becomes an additional chore. This reinforces the
negative bias towards the subject and prompts students to rely on “Google
searches” for answers on demand.

From the educator’s perspective, teaching MB in a case-based or
problem-based context to newly enrolled medical students with minimal medical
knowledge presents challenges. Since most traditional curricula provide limited
scope for reintroducing previously covered concepts into later discourse, the
clinical application of MB concepts is almost always absent in a traditional
pre-clerkship medical curriculum.

Harden
1
defines integration as “the organization of teaching matter to
interrelate or unify subjects frequently taught in separate academic courses or
departments”. When this organization spans across time and maintains
continuity, it represents a “longitudinal” integration approach.
When the organization occurs both within (intra) and amongst (inter) different
disciplines within a curriculum, it represents “horizontal”
integration.
2
Such integrative approaches can best be achieved in a
“spiral” curriculum
3
characterized by spaced repetition of clinically relevant concepts. Each
revisit, termed a “spiral”, aims to further elaborate on the
original concept through more advanced intra-and/or interdisciplinary
iterations.

Aiming to deliver MB with emphasis on the clinical relevance and inter/intra
subject connections, while exposing students to the complexity of the subject at
a gradual pace, we are invested in developing a detailed blueprint of an MB
curriculum featuring horizontal and longitudinal integration, combined with a
spiral delivery spanning across the pre-clerkship curriculum. We intend to share
a brief segment of our innovative pilot teaching effort on a few common basic
medical biochemistry topics with the Medical Education community worldwide
through this article.

TIPS FOR INTEGRATED TEACHING OF A FEW IMPORTANT
MEDICAL BIOCHEMISTRY TOPICS
1.
Teaching “Oxidative Fuel Metabolism” with an
integrated approach

Teaching “Oxidative Fuel Metabolism” with an
integrated approach

Initial presentation of Oxidative fuel metabolism
(“X”) : X includes core MB topics, namely glycolysis,
the tricarboxylic acid (TCA) cycle, the electron transport chain (ETC),
glycogenolysis, the pentose phosphate pathway, and their regulatory mechanisms,
all of which are high-yield in the pre-clerkship curriculum. Traditionally, X is
introduced to students at the inception of the curriculum with little to no
clinical context. At this time point, students often fail to comprehend the
practical or clinical relevance of “X” related concepts.

After the initial presentation of X, we made a conscious effort to integrate its
associated subtopics throughout the pre-clerkship curriculum. This involved
scrutinizing curricular materials through a multidisciplinary lens to identify
key intra- and inter-disciplinary connections to X and associated clinical
correlations ( Table 1 ). We invested
time in developing clinical scenarios for each connection. We then carefully
mapped the spiral delivery of X-related topics across different points in the
curriculum (outlined below). Our teaching efforts aimed to convey to students
the important message: “every pathological condition is caused by an
altered physiology, which in turn is manifested by an inherited or induced
biochemical/genetic alteration at the molecular level.”

Table 1. Ideas of spirally integrating “X” (oxidative fuel
metabolism) with multiple disciplines across different time points of
the pre-clerkship curriculum, post its presentation at the
inception. Initial
delivery of “X” (Oxidative Fuel Metabolism):
Inception of pre-clerkship curriculum; little to no clinical
context Spiral
delivery Longitudinal
integration in different Units/blocks Horizontal
integration with other disciplines Identified
topics for integration Context of
clinical integration
Spiral 1
Muscle and
movement Physiology Skeletal
muscle energetics Marathon,
Sprinting
Spiral 2
Cellular
pathogenesis Physiology,
hematology, pathology RBC
metabolism, oxygen transfer, cancer cell metabolism Hemolytic
anemias, Warburg effect
Spiral 3
Cardiovascular
and Renal Physiology,
pathophysiology Cardiac muscle
metabolism, renal tubular transport Myocardial
infraction, acute kidney injury
Spiral 4
Neurology Cell
physiology, neurobiology Neurotransmitter biosynthesis Multiple
sclerosis

Ideas of spirally integrating “X” (oxidative fuel
metabolism) with multiple disciplines across different time points of
the pre-clerkship curriculum, post its presentation at the
inception.

Spiral-1: Integrating X with muscle energetics and muscle
movement (physiology)

Spiraling back concepts of glycolysis, TCA, ETC, and glycogenolysis from the
introductory block of the pre-clerkship curriculum, into advanced discussions of
energy metabolism of type I (slow oxidative) and type II (fast glycolytic)
muscle fibers, highlighted the application of X in muscle energetics while
showcasing horizontal integration between biochemistry, physiology and
histology. Delivery of the content in the context of physical activities namely
marathon (type I dominated) and sprinting (type II dominated), highlighted the
role of X in athlete’s strength training, while integrating hormonal
(insulin, glucagon, epinephrine) and enzymatic (via AMP kinase) regulation of
muscle energetics and clinical treatment of the athlete’s dehydration
(dextrose infusions).

Spiral-2: Revisiting X in the context of hematology,
cellular pathogenesis, and nutrition

Integrating discussions of RBC metabolism, namely anaerobic glycolysis and the
pentose phosphate pathway (PPP), into hematology sessions focused on hemolytic
anemias allowed a review of X-linked concepts while applying them to the
pathogenesis of hemolytic anemias caused by glucose-6-phosphate dehydrogenase
(G-6-PD) deficiency and pyruvate kinase deficiency. The 2,3-bisphosphoglycerate
(2,3-BPG) shunt associated with glycolysis was “spiraled back”
into discussions of oxygen delivery by hemoglobin, the Bohr and Haldane effects
(physiology), and the clinical contexts of thalassemia, sickle cell anemia, and
hereditary persistence of fetal hemoglobin (HPFH). Revisiting glycolysis and TCA
in the context of vitamin deficiency diseases like Beriberi, emphasizing the
role of Vit B1 as a coenzyme for important mitochondrial enzymes such as the
pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase, is another
example of spiral integration. Glycolysis and PPP were again integrated into
discussions of cancer pathogenesis in the context of the Warburg effect (altered
metabolism of cancer cells), demonstrating a much higher level of horizontal
integration among biochemistry, hematology, and pathophysiology.

Spiral- 3: Integrating X with cardiovascular & renal
physiology & pathophysiology

A comparison of fuel choices between normal and ischemic cardiomyocytes in the
context of myocardial infarction re-emphasized the role of cellular fuels
(namely fatty acids, glucose, and ketones) in cardiac muscle function. This
comparison also highlighted horizontal integration between MB, cell biology,
histology, physiology, and pathology. Furthermore, concepts related to X were
seamlessly integrated into discussions of tubular transport and intra-renal
oxygenation mechanisms to highlight the differential metabolic needs of renal
cortical and medullary regions. Such integration also highlighted the role of
impaired fuel metabolism, driven by mitochondrial dysfunction, in the
pathogenesis of acute kidney injury (AKI).

Spiral-4: Integration of X with Neurology

The versatility of the glycolysis and the TCA cycle in different human cell types
were emphasized through focused discussions of excitatory and inhibitory
neurotransmitter synthesis using glycolytic and TCA intermediates. Examples
included glutamate synthesis from alpha-ketoglutarate, aspartate synthesis from
oxaloacetate, gamma amino butyric acid (GABA) synthesis from glutamate and
glycine synthesis using 3-phosphoglycerate. The discussions were framed within
the context of multiple sclerosis. 2.
Teaching “glucose and lipid metabolism” with an
integrated approach

Teaching “glucose and lipid metabolism” with an
integrated approach

Initial introduction of glucose and lipid metabolism in the
context of “Important Metabolic States” of the body

Fasting, fed, and starvation states are central metabolic conditions that anchor
many high-yield concepts for medical board exams, including STEP-I and COMLEX-I
in MD and osteopathic curricula. The fed state naturally frames discussions of
glucose absorption, the distribution and kinetics of various GLUT transporters,
the stimuli and mechanisms of insulin secretion from pancreatic β-cells,
and the insulin-driven upregulation of anabolic pathways—glycolysis,
glycogen synthesis, fatty acid synthesis, and protein synthesis—in
hepatocytes, adipocytes, and muscle cells. These processes support energy
production, nutrient storage, and overall metabolic homeostasis. When taught
through the simple lens of what occurs after consuming a glucose-rich meal(fed
state) enables rich, application-focused exploration of these pathways and
encourages horizontal integration of medical biochemistry with physiology and
introductory endocrinology.

The fasted and starved states provide a clear framework for teaching catabolic
pathways, including glycogenolysis, gluconeogenesis, lipolysis, fatty acid
oxidation, and ketogenesis, as illustrated in
Figure 1 . Emphasizing the roles of glycogenolysis and gluconeogenesis
in maintaining blood glucose homeostasis during fasting and early starvation,
along with the hormonal regulation of these pathways by glucagon and
epinephrine, supports high-yield, clinically grounded integration across
biochemistry, cell biology, and basic endocrinology. Expanding on the increasing
reliance on gluconeogenic precursors (lactate, pyruvate, alanine, aspartate),
lipolysis, and fatty acid oxidation during prolonged starvation—and the
progressive fuel shift from glucose to fatty acids and eventually to ketone
bodies—highlights how metabolic biochemistry underpins the body’s
adaptive survival strategies while conserving glucose for essential tissues.

Spiral integration of glucose and lipid metabolism concepts with
pathogenesis of Type 1 Diabetes mellitus (T1DM) and Type 2 Diabetes
mellitus (T2DM).

Abbreviations: I-Insulin; G-Glucagon; Sp-1: Spiral 1; Sp-2: Spiral 2

Spiral 1: Integrating glucose, lipid, and ketone metabolism
to explain the pathogenesis of Type I Diabetes Mellitus (T1DM)

Discussion of the pathogenesis of T1DM provides an effective framework for
demonstrating the clinical relevance of core metabolic biochemistry concepts
introduced at the start of the pre-clerkship curriculum. It links hyperglycemia
(elevated blood glucose levels), hypoinsulinemia (driven by low insulin
production or slow insulin secretion), and elevated glucagon levels to the
resulting hypercatabolic state, characteristic of T1DM, driven by a cellular
glucose deficit. This deficit activates multiple tissue-specific catabolic
pathways, creating an opportunity to revisit adipose tissue lipolysis, fatty
acid and ketone oxidation, hepatic ketogenesis, gluconeogenesis, and
glycogenolysis as compensatory mechanisms induced in patients with T1DM, all
aimed at mitigating the cellular energy crisis. These enriched spiral
discussions support horizontal integration across biochemistry, endocrine
physiology, and pathology in the context of T1DM pathophysiology, while also
explaining clinical manifestations such as rapid weight loss and ketoacidosis (
Figure 1 ). They highlight how
foundational metabolic principles connect directly to clinical applications
within an integrated pre-clerkship curriculum.

Spiral 2: Integrating glucose and lipid metabolism to
explain the pathogenesis of Type 2 Diabetes Mellitus (T2DM)

The pathogenesis of T2DM is typically covered in the endocrine block near the
end of the second year, when students have sufficient clinical background to
understand the condition’s complications. This provides another
opportunity to revisit insulin-driven anabolic pathways, such as fatty acid and
cholesterol biosynthesis, in the context of hyperinsulinemia caused by insulin
resistance. The hyperglycemia (high blood glucose level) caused by insulin
resistance provides a framework for integrating concepts from cell biology and
genetics, including mechanisms of receptor desensitization, inherited receptor
defects, and abnormalities in downstream signaling molecules, into discussions
of T2DM pathogenesis ( Figure 1 ). The
associated hyperlipidemia further enables integration of adipose tissue
endocrine functions, particularly leptin and adiponectin secretion, with insulin
resistance. These discussions model broad, in-depth horizontal integration
across biochemistry, cell biology, physiology, and endocrinology, while linking
metabolic biochemistry concepts to their clinical relevance. The clear
mechanistic connections between molecular pathways and real clinical diseases
often energize students by showing how foundational knowledge directly explains
patient presentations. Repeated exposure to these themes across the
pre-clerkship curriculum also reinforces longitudinal curricular
integration.

Potential outcomes of our novel teaching initiative

1.
Potential benefits for medical students
•
Promotion of deeper understanding and
longer-term retention of subject knowledge
Our novel integrated teaching effort of MB related concepts would help
students correlate the conceptual knowledge (‘what’) with
the strategic knowledge (‘how’) and the conditional
knowledge (‘why’), thereby promoting deeper understanding,
long-term memory, and better preparedness for medical board exams (USMLE
STEP I and COMLEX-I) and their future clerkship education. As
biochemistry educators, we strongly believe that a deeper, integrated
understanding of metabolism doesn’t just help students pass exams
in the medical curriculum, it helps develop a mechanistic mindset in
medical students, which they carry into clinical practice. It also
meaningfully shapes the kind of diabetes care they will deliver as
future physicians. Such a model can also be easily adopted by other fundamental
sciences. •
Fostering the development of critical
thinking and problem-solving skills
The existing literature emphasizes the significant association among
elements of the curriculum (content, objectives, methods, and
assessments), factual knowledge, and a disposition toward critical
thinking.
4
The pre-clerkship curriculum period is the only time in the
entire professional career of an aspiring physician when the
fundamentals of biomedical sciences and clinical skills (such as
history-taking and physical exams) intersect and are formally taught and
learnt. Through spaced repetition (spiral delivery), continual practice,
and critical appraisal of interdisciplinary connections in clinical
contexts, this curricular model would facilitate an earlier and more
cohesive development of critical thinking and problem-solving skills in
medical students, as was evident at our institutions (through their
in-class interactions and internal exam performances). These crucial
traits are expected to contribute significantly towards students’
success in clerkship education and future medical practice.
5

2.
Potential benefits for medical biochemistry educators
Indeed, we predict that participation in this model of teaching across
multidisciplinary domains would provide a satisfactory teaching
experience for biochemistry educators and would likely lead to greater
recognition and appreciation from both medical students and medical
school administrators. The model also has the potential to be easily
adopted by other fundamental sciences and yield similar promising
outcomes. 3.
Assembling an interdisciplinary curriculum team invested in a
common goal
The integrated approach to teaching MB would facilitate the breakdown of
interdisciplinary and inter-departmental boundaries, helping establish a
cohesive team of faculty members and administrators all dedicated to a
common goal of highly skilled classroom teaching.

Potential benefits for medical students

Promotion of deeper understanding and
longer-term retention of subject knowledge

Our novel integrated teaching effort of MB related concepts would help
students correlate the conceptual knowledge (‘what’) with
the strategic knowledge (‘how’) and the conditional
knowledge (‘why’), thereby promoting deeper understanding,
long-term memory, and better preparedness for medical board exams (USMLE
STEP I and COMLEX-I) and their future clerkship education. As
biochemistry educators, we strongly believe that a deeper, integrated
understanding of metabolism doesn’t just help students pass exams
in the medical curriculum, it helps develop a mechanistic mindset in
medical students, which they carry into clinical practice. It also
meaningfully shapes the kind of diabetes care they will deliver as
future physicians.

Such a model can also be easily adopted by other fundamental
sciences.

Fostering the development of critical
thinking and problem-solving skills

The existing literature emphasizes the significant association among
elements of the curriculum (content, objectives, methods, and
assessments), factual knowledge, and a disposition toward critical
thinking.
4
The pre-clerkship curriculum period is the only time in the
entire professional career of an aspiring physician when the
fundamentals of biomedical sciences and clinical skills (such as
history-taking and physical exams) intersect and are formally taught and
learnt. Through spaced repetition (spiral delivery), continual practice,
and critical appraisal of interdisciplinary connections in clinical
contexts, this curricular model would facilitate an earlier and more
cohesive development of critical thinking and problem-solving skills in
medical students, as was evident at our institutions (through their
in-class interactions and internal exam performances). These crucial
traits are expected to contribute significantly towards students’
success in clerkship education and future medical practice.
5

Potential benefits for medical biochemistry educators

Indeed, we predict that participation in this model of teaching across
multidisciplinary domains would provide a satisfactory teaching
experience for biochemistry educators and would likely lead to greater
recognition and appreciation from both medical students and medical
school administrators. The model also has the potential to be easily
adopted by other fundamental sciences and yield similar promising
outcomes.

Assembling an interdisciplinary curriculum team invested in a
common goal

The integrated approach to teaching MB would facilitate the breakdown of
interdisciplinary and inter-departmental boundaries, helping establish a
cohesive team of faculty members and administrators all dedicated to a
common goal of highly skilled classroom teaching.

Conclusion : Aiming for a bigger gain in the future

Positive student feedback (as part of the regular student evaluation for these
sessions) on the pilot integrated teaching effort for selected MB concepts has
motivated the authors to develop a full roadmap for an integrated pre-clerkship MB
curriculum. The planned curriculum will use updated materials, consistent delivery
methods, and ongoing evaluation of its impact on student success. Once completed and
published, the project will serve as a faculty development resource and help modern
medical educators of the 21 st century move beyond the outdated
two-pillar Flexner
6
model, which for years separated the delivery of foundational and clinical
sciences in medical education.

Ethical statement

This article reflects a snapshot of the authors’ educational initiative as
medical educators and does not involve a research study. No human participants were
recruited, no identifiable learner or patient data were collected, and no
interventions were conducted for research purposes. Ethical approval was therefore
not required. All reflections and examples are drawn from the authors’
professional experience.